FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Santo, ARE Bartlett, JD Gibson, CW Li, Y Kulkarni, AB Line, SRP AF Espirito Santo, Alexandre R. Bartlett, John D. Gibson, Carolyn W. Li, Yong Kulkarni, Ashok B. Line, Sergio R. P. TI Amelogenin- and enamelysin (Mmp-20)-deficient mice display altered birefringence in the secretory-stage enamel organic extracellular matrix SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE amelogenin; birefringence; enamel organic extracellutar matrix; enamelysin; knockout ID DEVELOPING DENTAL ENAMEL; HYDROXYAPATITE CRYSTALS; RECOMBINANT AMELOGENIN; IMPERFECTA PHENOTYPE AB Dental enamel is the most mineralized tissue of vertebrate organisms. Enamel biosynthesis is initiated by the secretion, processing, and self-assembly of a complex mixture of proteins. The formation of an ordered enamel organic extracellular matrix (ECM) seems be a crucial step for the proper formation of mineral phase. Polarizing microscopy demonstrates that the ordered supramolecular structure of the secretory-stage enamel organic ECM is strongly birefringent. In the present work we analyzed the birefringence of secretory-stage enamel organic ECM in amelogenin (Amelx)- and enamelysin (Mmp20)-deficient mice. Female Amelx(+/-) animals showed significant reduction in optical retardation values when compared with the Amelx(+/+) subgroup (p = 0.0029). The secretory-stage enamel organic ECM of the Amelx(-/-) subgroup did not exhibit birefringence. The secretory-stage enamel organic ECM of Mmp20(-/-) mice showed a significant decrease in optical retardation as compared with Mmp20(+/+) and Mmp20(+/-) mice (p = 0.0000). Minp20(+/-) and Mmp20(+/+) mice exhibited similar birefringence (p = 1.0000). The results presented here support growing evidence for the idea that the birefringence of secretory-stage enamel organic ECM is influenced by the ordered supramolecular organization of its components. C1 Univ Estadual Campinas, Fac Odontol, Dept Morphol, Sch Dent, BR-13414903 Piracicaba, SP, Brazil. Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst,Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Line, SRP (reprint author), Univ Estadual Campinas, Fac Odontol, Dept Morphol, Sch Dent, Ave Limeira,901 Areiao,Postal 52, BR-13414903 Piracicaba, SP, Brazil. EM serglin@fop.unicamp.br RI Line, Sergio/H-5272-2012 OI Line, Sergio/0000-0002-6574-9464 NR 23 TC 8 Z9 9 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-8207 EI 1607-8438 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2007 VL 48 IS 1 BP 39 EP 45 DI 10.1080/03008200601059175 PG 7 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 140TK UT WOS:000244529400006 ER PT J AU Konrad, N Daigle, MS Daniel, AE Dear, GE Frottier, P Hayes, LM Kerkhof, A Liebling, A Sarchiapone, M AF Konrad, Norbert Daigle, Marc S. Daniel, Anasseril E. Dear, Greg E. Frottier, Patrick Hayes, Lindsay M. Kerkhof, Ad Liebling, Alison Sarchiapone, Marco TI Preventing suicide in prisons, part I - Recommendations from the International Association for Suicide Prevention Task Force on Suicide in Prisons SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE prison; suicide; prevention; inmate; suicide attempt ID DISTINGUISHING FEATURES; RISK-FACTORS; SELF-HARM; BEHAVIOR; INMATES; ATTEMPTERS; JAIL AB In 2000 the Department of Mental Health of the World Health Organization (WHO) published a guide named Preventing Suicide. A Resource for Prison Officers as part of the WHO worldwide initiative for the prevention of suicide. In 2007 there are new epidemiological data on prison suicide, a more detailed discussion of risk factors accounting for the generally higher rate of suicide in correctional settings in comparison to the general population, and several strategies for developing screening instruments. As a first step, this paper presents an update of the WHO guide by the Task Force on Suicide in Prisons, created by the International Association for Suicide Prevention. A second paper, by the same Task Force, will present some international comparisons of suicide prevention services in correctional facilities. C1 [Konrad, Norbert] Inst Forens Psychiat Charite, D-13627 Berlin, Germany. [Konrad, Norbert] Berlin Prison Hosp, Dept Psychiat & Psychotherapy, Berlin, Germany. [Konrad, Norbert] Univ Quebec, Trois Rivieres, PQ GA9 5H7, Canada. [Daigle, Marc S.] CRISE, Trois Rivieres, PQ, Canada. [Daigle, Marc S.] Univ Missouri, Sch Med, Columbia, MO USA. [Daigle, Marc S.] Edith Cowan Univ, Joondalup, Australia. [Daniel, Anasseril E.] JA Mittersteig, Vienna, Austria. [Dear, Greg E.] Natl Ctr Inst & Alternat, Mansfield, MA USA. [Frottier, Patrick] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Hayes, Lindsay M.] Cambridge Inst Criminol, Cambridge, England. [Kerkhof, Ad] Univ Cambridge, Cambridge CB2 1TN, England. [Liebling, Alison] Univ Molise, Campobasso, Italy. RP Konrad, N (reprint author), Inst Forens Psychiat Charite, Saatwinkler Damm 1A, D-13627 Berlin, Germany. EM norbert.konrad@charite.de OI Sarchiapone, Marco/0000-0001-9583-3117 NR 49 TC 42 Z9 44 U1 5 U2 23 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0227-5910 J9 CRISIS JI Crisis PY 2007 VL 28 IS 3 BP 113 EP 121 DI 10.1027/0227-5910.28.3.113 PG 9 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 239VD UT WOS:000251545500002 PM 17992824 ER PT J AU Daigle, MS Daniel, AE Dear, GE Frottier, P Hayes, LM Kerkhof, A Konrad, N Liebling, A Sarchiapone, M AF Daigle, Marc S. Daniel, Anasseril E. Dear, Greg E. Frottier, Patrick Hayes, Lindsay M. Kerkhof, Ad Konrad, Norbert Liebling, Alison Sarchiapone, Marco TI Preventing suicide in prisons, part II - International comparisons of suicide prevention services in correctional facilities SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE prison; suicide; prevention; inmate; suicide attempt AB The International Association for Suicide Prevention created a Task Force on Suicide in Prisons to better disseminate the information in this domain. One of its objectives was to summarize suicide-prevention activities in the prison systems. This study of the Task Force uncovered many differences between countries, although mental health professionals remain central in all suicide prevention activities. Inmate peer-support and correctional officers also play critical roles in suicide prevention but there is great variation in the involvement of outside community workers. These differences could be explained by the availability of resources, by the structure of the correctional and community services, but mainly by the different paradigms about suicide prevention. While there is a common and traditional paradigm that suicide prevention services are mainly offered to individuals by mental health services, correctional systems differ in the way they include (or not) other partners of suicide prevention: correctional officers, other employees, peer inmates, chaplains/priests, and community workers. Circumstances, history, and national cultures may explain such diversity but they might also depend on the basic way we think about suicide prevention at both individual and environmental levels. C1 [Daigle, Marc S.] Univ Quebec, Philippe Pinel Inst Montreal, CRISE, Trois Rivieres, PQ G9A 5H7, Canada. [Daigle, Marc S.] Univ Missouri, Sch Med, Columbia, MO USA. [Daniel, Anasseril E.] Edith Cowan Univ, Joondalup, Australia. [Dear, Greg E.] JA Mittersteig, Vienna, Austria. [Frottier, Patrick] Natl Ctr Inst & Alternat, Mansfield, PA USA. [Hayes, Lindsay M.] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Kerkhof, Ad] Inst Forens Psychiat Charite, Berlin, Germany. [Konrad, Norbert] Cambridge Inst Criminol, Cambridge, England. [Konrad, Norbert] Univ Cambridge, Cambridge CB2 1TN, England. [Konrad, Norbert] Univ Molise, Campobasso, Italy. [Liebling, Alison] World Psychiat Assoc, Suicidol Sect, New York, NY 10029 USA. RP Daigle, MS (reprint author), Univ Quebec, Philippe Pinel Inst Montreal, CRISE, POB 500, Trois Rivieres, PQ G9A 5H7, Canada. EM marc.daigle@uqtr.ca OI Sarchiapone, Marco/0000-0001-9583-3117 NR 20 TC 18 Z9 18 U1 2 U2 19 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0227-5910 J9 CRISIS JI Crisis PY 2007 VL 28 IS 3 BP 122 EP 130 DI 10.1027/0227-5910.28.3.122 PG 9 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 239VD UT WOS:000251545500003 PM 17992825 ER PT J AU Drake, JW AF Drake, John W. TI Too many mutants with multiple mutations SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE spontaneous mutation; mutational clusters; hypermutation ID ESCHERICHIA-COLI K-12; DNA-POLYMERASE-BETA; SPONTANEOUS HPRT MUTATIONS; BLUE(R) TRANSGENIC MICE; SIMPLEX-VIRUS TYPE-1; SACCHAROMYCES-CEREVISIAE; SPONTANEOUS MUTAGENESIS; SEQUENCE-ANALYSIS; ERROR-PRONE; IN-VIVO AB It has recently become clear that the classical notion of the random nature of mutation does not hold for the distribution of mutations among genes: most collections of mutants contain more isolates with two or more mutations than predicted by the mutant frequency on the assumption of a random distribution of mutations. Excesses of multiples are seen in a wide range of organisms, including riboviruses, DNA viruses, prokaryotes, yeasts, and higher eukaryotic cell lines and tissues. In addition, such excesses are produced by DNA polymerases in vitro. These "multiples" appear to be generated by transient, localized hypermutation rather than by heritable mutator mutations. The components of multiples are sometimes scattered at random and sometimes display an excess of smaller distances between mutations. As yet, almost nothing is known about the mechanisms that generate multiples, but such mutations have the capacity to accelerate those evolutionary pathways that require multiple mutations where the individual mutations are neutral or deleterious. Examples that impinge on human health may include carcinogenesis and the adaptation of microbial pathogens as they move between individual hosts. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov FU Intramural NIH HHS [Z01 ES065016-08] NR 63 TC 47 Z9 47 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PY 2007 VL 42 IS 4 BP 247 EP 258 DI 10.1080/10409230701495631 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202ZE UT WOS:000248943000002 PM 17687667 ER PT J AU Millet, C Zhang, YE AF Millet, Caroline Zhang, Ying E. TI Roles of Smad3 in TGF-beta signaling during carcinogenesis SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Review DE tumor suppressor; growth inhibition; apoptosis; metastasis; immune suppression; transcription ID GROWTH-FACTOR-BETA; II RECEPTOR GENE; CELL-CYCLE ARREST; P38 MAP KINASE; TO-MESENCHYMAL TRANSITION; CDK INHIBITOR P15(INK4B); EPITHELIAL TUMOR-CELLS; C-MYC; MICROSATELLITE INSTABILITY; BREAST-CANCER AB Signaling of transforming growth factor beta (TGF-beta) is mediated through a heteromeric complex of two types of transmembrane receptors and downstream intracellular proteins known as Smads. Alterations of TGF-P signaling underlie various forms of human cancer and developmental diseases. Human genetic studies have revealed both point mutations and deletions of Smad2 or Smad4 in several types of cancers. However, the role of Smad3 in turnorigenesis is not clear. Recent data indicate that Smad3 also functions as a tumor suppressor by inhibiting cell proliferation and promoting apoptosis. In addition, Smad3 is essential for TGF-p-mediated immune suppression, and it plays an important role in regulating transcriptional responses that are favorable to metastasis. Therefore, through regulating different transcriptional responses, Smad3 functions as both a negative and positive regulator of carcinogenesis depending on cell type and clinical stage of the tumor. C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zhang, YE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 2056B, Bethesda, MD 20892 USA. EM yingz@helix.nih.gov RI Zhang, Ying/G-3657-2015 OI Zhang, Ying/0000-0003-2753-7601 FU Intramural NIH HHS [Z01 BC010419-08] NR 114 TC 29 Z9 32 U1 0 U2 1 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1045-4403 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 2007 VL 17 IS 4 BP 281 EP 293 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 197YZ UT WOS:000248594700003 PM 17725494 ER PT J AU Yarchoan, R Pluda, JM Wyvill, KM Aleman, K Rodriguez-Chavez, IR Tosato, G Catanzaro, AT Steinberg, SM Little, RF AF Yarchoan, Robert Pluda, James M. Wyvill, Kathleen M. Aleman, Karen Rodriguez-Chavez, Isaac R. Tosato, Giovanna Catanzaro, Andrew T. Steinberg, Seth M. Little, Richard F. TI Treatment of AIDS-Related Kaposi's sarcoma with interleukin-12: Rationale and preliminary evidence of clinical activity SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE cytokine; immunotherapy; human immunodeficiency virus; angiogenesis; Kaposi's sarcomaassociated herpesvirus; human herpesvirus type 8 ID RECOMBINANT HUMAN INTERLEUKIN-12; HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-COUPLED RECEPTOR; ANGIOGENESIS IN-VIVO; RENAL-CELL CARCINOMA; T-REGULATORY-CELLS; PHASE-II TRIAL; ANTIRETROVIRAL THERAPY; HOMOSEXUAL MEN; ENDOTHELIAL-CELLS AB In this article, we review the preliminary evidence for the activity of interleukin-12 (IL-12) against Kaposi's sarcoma (KS) and discuss these results in the context of the biology of IL-12 and KS. IL-12 is a cytokine that enhances type 1 immunity, induces production of interferon gamma (IFN-gamma), and mediates antiangiogenic effects. In addition, it can downregulate a constitutively active G protein coupled receptor that is encoded by Kaposi's sarcoma-associated herpesvirus, the causative agent of KS. These factors suggested that IL-12 might be worth exploring as a potential anti-KS agent. In an initial phase I pilot study, IL-12 was found to have anti-KS activity when used alone in patients with AIDS-associated KS who were on a stable regimen of antiretroviral therapy. In preliminary results from a subsequent study of the combination of IL-12 plus liposomal doxorubicin along with highly active antiretroviral therapy, remissions were obtained in a substantial percentage of patients with advanced AIDS-associated KS. IL-12 has also been found active in patients with certain lymphomas. These results suggest that IL-12 may be worth exploring further as a potential antitumor agent in selected tumors. C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bldg 10,Rm 6N106,MSC 1868, Bethesda, MD 20892 USA. EM yarchoan@helix.nih.gov FU Intramural NIH HHS NR 84 TC 16 Z9 16 U1 0 U2 1 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2007 VL 27 IS 5 BP 401 EP 414 PG 14 WC Immunology SC Immunology GA 231SM UT WOS:000250969300001 PM 18197804 ER PT J AU Jin, P Wang, E Provenzano, M Stroncekl, D Marincoial, FM AF Jin, Ping Wang, Ena Provenzano, Maurizio Stroncekl, David Marincoial, Francesco M. TI Gene expression signatures of interleukin-2 in vivo and in vitro and their relation to anticancer therapy SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE functional genomics; immunotherapy; interleukin-2; melanoma; microarray; renal cell cancer ID HIGH-DOSE INTERLEUKIN-2; RENAL-CELL CARCINOMA; ACTIVATED KILLER-CELLS; CARBONIC-ANHYDRASE-IX; REGULATORY T-CELLS; PHASE-III TRIAL; METASTATIC MELANOMA; IMMUNE RESPONSIVENESS; ANTITUMOR-ACTIVITY; INFECTED PATIENTS AB Treatment with human recombinant interleukin-2 (rIL-2) can successfully eradicate advanced cancer in humans; however, its utilization is limited by the unpredictability of its effectiveness and the excessive toxicity often associated with its use. The mechanisms responsible for immune-mediated tumor regression and those associated with limiting toxicity have not yet been sorted out. Thus, this review critically addresses what has been done in the past to understand this biologically and practically important question and discusses future strategies to enhance the understanding of this interesting model of immune-mediated tumor rejection. In particular, the first aim of this review is to discuss what is known about the mechanism(s) responsible for tumor rejection; the second aim is to review the relationship between the toxicity induced by rIL-2 treatment and its effectiveness; the third aim is to summarize novel insights into the possible mechanism of rIL-2 activity in vivo using high-throughput strategies aimed at the global assessment in real-time of events associated with rIL-2 therapy in humans. This information will not only lead to a better utilization of this biological agent in clinical practice but it may also provide important information about how immune-mediated tissue rejection occurs. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Hosp ZLF, Dept Surg, Immune Oncol Sect, CH-4031 Basel, Switzerland. RP Marincoial, FM (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C-711,10 Ctr Dr MSC 1502, Bethesda, MD 20892 USA. EM FMarincola@mail.cc.nih.gov NR 71 TC 13 Z9 14 U1 0 U2 1 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2007 VL 27 IS 5 BP 437 EP 448 PG 12 WC Immunology SC Immunology GA 231SM UT WOS:000250969300003 PM 18197806 ER PT J AU Arlen, PM Gulley, JL Madan, RA Hodge, JW Schlom, J AF Arlen, Philip M. Gulley, James L. Madan, Ravi A. Hodge, James W. Schlom, Jeffrey TI Preclinical and clinical studies of recombinant poxvirus Vaccines for carcinoma therapy SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE immunotherapy; vaccines; tumor antigens; costimulation ID INDEPENDENT PROSTATE-CANCER; FAS-MEDIATED CYTOTOXICITY; COLONY-STIMULATING FACTOR; RANDOMIZED PHASE-II; IMMUNE-RESPONSES; COSTIMULATORY MOLECULES; ANTITUMOR IMMUNITY; ANTIGEN-EXPRESSION; DIVERSIFIED PRIME; GAMMA-INTERFERON AB Tumor-associated antigens (TAAs) are by definition either weakly immunogenic or fiinctionally nonimmunogenic. Vaccine strategies have been designed to present TAAs to the immune system that may result in far greater activation of T cells than that occurring naturally in the host. These strategies include (1) placing the gene coding for the tumor antigen into poxvirus vectors as a transgene; (2) using diversified prime-and-boost vaccine strategies employing two different types of poxvirus vectors; (3) using T-cell costimulation; and (4) using cytokines, including GM-CSF, as biologic adjuvants. Preclinical studies have been performed comparing the effects on induction of antigen-specific CD8 and CD4 T-cell responses using recombinant poxvirus vectors containing transgenes for a TAA and costimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM). Antigen-specific T-cell responses were greatest in the group receiving the CEA-TRICOM vaccines and were shown to correlate with survival. We have now completed the first clinical trials with poxvirus vectors containing TRICOM, using the TAAs PSA, CEA, and MUC-1. In addition, clinical studies combining vaccines with radiation therapy, chemotherapy, and second-line hormone therapy have provided preliminary evidence of prolongation of time to disease progression and "antigen cascade" postvaccination. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Arlen, PM (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM arlenp@mail.nih.gov RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016 OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912 NR 51 TC 31 Z9 32 U1 0 U2 2 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2007 VL 27 IS 5 BP 451 EP 462 PG 12 WC Immunology SC Immunology GA 231SM UT WOS:000250969300004 PM 18197807 ER PT J AU Garcia-Diaz, M Bebenek, K AF Garcia-Diaz, Miguel Bebenek, Katarzyna TI Multiple functions of DNA polymerases SO CRITICAL REVIEWS IN PLANT SCIENCES LA English DT Review DE DNA polymerase; DNA repair; DNA replication; TLS; translesion synthesis; fidelity ID BASE EXCISION-REPAIR; CELL-NUCLEAR ANTIGEN; STRAND BREAK REPAIR; XERODERMA-PIGMENTOSUM VARIANT; PHOSPHATE LYASE ACTIVITY; INTERSTRAND CROSS-LINKS; SYN THYMINE DIMER; ORYZA-SATIVA L.; MU POL-MU; ESCHERICHIA-COLI AB The primary role of DNA polymerases is to accurately and efficiently replicate the genome to ensure the maintenance of the genetic information and its faithful transmission through generations. This is not a simple task considering the size of the genome and its constant exposure to endogenous and environmental DNA damaging agents. Thus, a number of DNA repair pathways operate in cells to protect the integrity of the genome. In addition to their role in replication, DNA polymerases play a central role in most of these pathways. Given the multitude and the complexity of DNA transactions that depend on DNA polymerase activity, it is not surprising that cells in all organisms contain multiple highly specialized DNA polymerases, the majority of which have only recently been discovered. Five DNA polymerases are now recognized in Escherichia coli, 8 in Saccharomyces cerevisiae, and at least 15 in humans. While polymerases in bacteria, yeast, and mammalian cells have been extensively studied much less is known about their counterparts in plants. For example, the plant model organism Arabidopsis thaliana is thought to contain 12 DNA polymerases, whose functions are mostly unknown. Here we review the properties and functions of DNA polymerases focusing on yeast and mammalian cells but paying special attention to the plant enzymes and the special circumstances of replication and repair in plant cells. C1 NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Bebenek, K (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM bebenek@niehs.nih.gov FU Intramural NIH HHS [Z01 ES065070-17] NR 195 TC 24 Z9 24 U1 4 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-2689 J9 CRIT REV PLANT SCI JI Crit. Rev. Plant Sci. PY 2007 VL 26 IS 2 BP 105 EP 122 DI 10.1080/07352680701252817 PG 18 WC Plant Sciences SC Plant Sciences GA 161LP UT WOS:000246016700002 PM 18496613 ER PT J AU Rausch, JW Le Grice, SFJ AF Rausch, Jason W. Le Grice, Stuart F. J. TI Exploiting structurally diverse nucleoside analogs as probes of reverse transcription complexes SO CURRENT HIV RESEARCH LA English DT Review ID TYPE-1 POLYPURINE TRACT; MURINE LEUKEMIA-VIRUS; STRAND DNA-SYNTHESIS; RNASE-H CLEAVAGE; IMMUNODEFICIENCY-VIRUS; RIBONUCLEASE-H; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; TEMPLATE-PRIMER; RNA/DNA HYBRIDS AB Crystal structures of HIV-1 reverse transcriptase (RT) in complex with either duplex DNA or an RNA/DNA hybrid have provided significant insights into the manner in which this highly versatile enzyme accommodates the conformationally-distinct nucleic acid substrates encountered during the reverse transcription cycle. Biochemical data likewise suggest that unique structural features of the nucleic acid substrates contribute towards recognition by their cognate RT. While site-directed mutagenesis of catalytically- and structurally-critical protein motifs is relatively facile, understanding how nucleic acid structure contributes to its recognition presents a greater challenge. The relative ease with which large DNA and RNA fragments can now be chemically synthesized, in conjunction with the increased availability of ribo- and deoxyribonucleoside analogs, allows nucleic acid structure to be examined with respect to the role of hydrogen bonding, nucleobase stacking, sugar ring geometry and charge of the phosphodiester backbone. This review summarizes our use of nucleoside analogs to understand how the structure of cis-acting regulatory signals mediates their recognition by structurally diverse retroviral and retrotransposon enzymes. C1 Natl Canc Inst, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), Natl Canc Inst, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM slegrice@ncifcrf.gov NR 63 TC 4 Z9 4 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JAN PY 2007 VL 5 IS 1 BP 11 EP 22 DI 10.2174/157016207779316332 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 126GW UT WOS:000243501800002 PM 17266554 ER PT J AU Cai, LS Innis, RB Pike, VW AF Cai, Lisheng Innis, Robert B. Pike, Victor W. TI Radioligand development for PET imaging of beta-amyloid (AD)-current status SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE PET imaging; beta-amyloid; radioligand; assay; Alzheimer's disease ID POSITRON-EMISSION-TOMOGRAPHY; ONSET ALZHEIMERS-DISEASE; PITTSBURGH COMPOUND-B; X-RAY-DIFFRACTION; NUCLEAR-MAGNETIC-RESONANCE; ATOMIC-FORCE MICROSCOPY; TRANSGENIC MOUSE MODELS; CENTRAL-NERVOUS-SYSTEM; IN-VIVO; APOLIPOPROTEIN-E AB Two of the main pathological hallmarks of Alzheimer's disease (AD) are neuritic plaques and neurofibrillary tangles. Significant evidence supports a critical and probable causative role of beta amyloid (A beta) plaque formation. Since neuroprotective treatments are typically most effective at early stages of injury, the detection and measurement of AD load in living brain should be performed at early and perhaps even presymptornatic stages of AD. Two primary targets of molecular imaging research with positron emission tomography (PET) are to develop surrogate markers (radioligands) for assessing disease progression and for monitoring the efficacy of developmental therapeutics. Here, we review the current status of radioligand development for PET imaging of A beta aggregates. General structure-activity relationships have emerged, including the identification of at least three different ligand binding sites in various A beta aggregates and recognition of the general structural requirements for ligand binding at each site. Also a few radioligands applicable to imaging A beta plaques in living human brain with positron emission tomography (PET) have emerged, including [C-11]PIB, [C-11]SB-13 and [F-18]FDDNP. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Cai, LS (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM cail@intra.nimh.nih.gov FU Intramural NIH HHS NR 179 TC 93 Z9 95 U1 2 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2007 VL 14 IS 1 BP 19 EP 52 DI 10.2174/092986707779313471 PG 34 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 122TA UT WOS:000243248500002 PM 17266566 ER PT J AU Yeung, ML Bennasser, Y Jeang, KT AF Yeung, Man Lung Bennasser, Yamina Jeang, Kuan-Teh TI miRNAs in the biology of cancers and viral infections SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE non-coding small RNA; microrna; carcinogenesis; tumorigenesis; viral pathogenesis ID TRANSCRIPTIONAL REGULATORY NETWORKS; MICRORNA EXPRESSION PROFILES; RNA-BINDING PROTEIN; HUMAN-CELLS; REDUCED EXPRESSION; ENCODED MICRORNAS; GENE-EXPRESSION; NUCLEAR EXPORT; MESSENGER-RNAS; COLON-CANCER AB MicroRNAs (miRNAs) are non-coding small RNAs that play important roles in a variety of biological pathways including cellular proliferation and apoptosis. Recent studies have linked the expression of selected miRNAs to carcinogenesis and viral pathogenesis. Here, we will discuss examples of roles served by cellular miRNAs and virus-encoded miRNAs in the development of cancers and viral diseases. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 77 TC 15 Z9 18 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2007 VL 14 IS 2 BP 191 EP 197 DI 10.2174/092986707779313417 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 122TC UT WOS:000243248700006 PM 17266578 ER PT J AU Gupta, R Brosh, RM AF Gupta, Rigu Brosh, Robert M., Jr. TI DNA repair helicases as targets for anti-cancer therapy SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE helicase; DNA repair; RecQ; Fanconi anemia; cancer; chemotherapy; anti-cancer drug; telomere ID WERNER-SYNDROME PROTEIN; ROTHMUND-THOMSON-SYNDROME; INTERSTRAND CROSS-LINKS; BLOOMS-SYNDROME HELICASE; RECQ FAMILY HELICASES; FANCONI ANEMIA/BRCA PATHWAY; STRAND-ANNEALING ACTIVITIES; BASE EXCISION-REPAIR; CELL LUNG-CANCER; FUNCTIONAL INTERACTION AB The genetic complexity of cancer has posed a formidable challenge to devising successful therapeutic treatments. Tumor resistance to cytotoxic chemotherapy drugs and radiation which induce DNA damage has limited their effectiveness. Targeting the DNA damage response is a strategy for combating cancer. The prospect for success of chemotherapy treatment may be improved by the selective inactivation of a DNA repair pathway. A key class of proteins involved in various DNA repair pathways is comprised of energy-driven nucleic acid unwinding enzymes known as helicases. DNA helicases have been either implicated or have proposed roles in nucleotide excision repair, mismatch repair, base excision repair, double strand break repair, and most recently cross-link repair. In addition to DNA repair, helicases have been implicated in the cellular processes of replication, recombination, transcription, and RNA stability/processing. The emerging evidence indicates that helicases have vital roles in pathways necessary for the maintenance of genomic stability. In support of this, a growing number of human genetic disorders are attributed to mutations in helicase genes. Because of their essential roles in nucleic acid metabolism, and more specifically the DNA damage response, helicases may be a suitable target of chemotherapy. In this review, we have explored this hypothesis and provided a conceptual framework for combinatorial treatments that might be used for combating cancer by inhibiting helicase function in tumor cells that already have compromised DNA repair and/or DNA damage signaling. This review is focused on helicase pathways, with a special emphasis on DNA cross-link repair and double strand break repair, that impact cancer biology and how cancer cells may be chemosensitized through the impairment of helicase function. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM broshr@grc.nia.nih.gov FU Intramural NIH HHS NR 144 TC 17 Z9 18 U1 3 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2007 VL 14 IS 5 BP 503 EP 517 DI 10.2174/092986707780059706 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 133IW UT WOS:000244007600001 PM 17346143 ER PT J AU Maher, SG Romero-Weaver, AL Scarzello, AJ Gamero, AM AF Maher, S. G. Romero-Weaver, A. L. Scarzello, A. J. Gamero, A. M. TI Interferon: Cellular executioner or white knight? SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE interferon; interferon receptor; antiviral; immunomodulation; apoptosis; JAK/STAT signaling; clinical applications; cancer ID ACTIVATED PROTEIN-KINASE; ALPHA-INDUCED APOPTOSIS; MEDIATES TYROSINE PHOSPHORYLATION; RESISTANT PULMONARY TUBERCULOSIS; NUCLEAR-LOCALIZATION SEQUENCE; CHRONIC GRANULOMATOUS-DISEASE; REMITTING MULTIPLE-SCLEROSIS; PROSPECTIVE RANDOMIZED-TRIAL; CHRONIC MYELOGENOUS LEUKEMIA; HUMAN GAMMA-INTERFERON AB Interferons (IFNs) are a family of pleiotropic cytokines that typically exhibit antiviral, antiproliferative, antitumor, and immunomodulatory properties. While their complex mechanisms of action remain unclear, IFNs are used clinically in the treatment of viral infections, such as hepatitis B and hepatitis C, and remain the primary treatment for a limited number of malignancies, such as melanoma, hairy cell leukemia, and non-Hodgkin's lymphoma and in autoimmune diseases such as multiple sclerosis. IFNs not only regulate somatic cell growth and division but also influence cell survival through the modulation of apoptosis. Paradoxically, IFNs are described to be both pro- and anti-apoptotic in nature. The biological effects of IFNs are primarily mediated via activation of the JAK/STAT pathway, formation of the ISGF3 and STAT1:STAT1 protein complexes, and the subsequent induction of IFN-stimulated genes. However, the activation of JAK/STAT-independent signal transduction pathways also contribute to IFN-mediated responses. To further demonstrate the complexity of the downstream events following stimulation, oligonucleotide microarray studies have shown that in excess of 300 genes are induced following treatment with IFN, some of which are crucial to the induction of apoptosis and cell growth control. In this review we describe the recent advances made in elucidating the various signaling pathways that are activated by IFNs and how these diverse signals contribute to the regulation of cell growth and apoptosis and inhibition of viral replication. Furthermore, we highlight the role of specific signaling molecules and the function(s) of particular IFN-stimulated genes that have been implicated in determining cell fate in response to IFN, as well as the clinical experience of IFN immunotherapy. C1 NCI, Canc & Inflammat Program, Expt Immunol Lab, NIH, Ft Detrick, MD 21702 USA. RP Gamero, AM (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, NIH, Bldg 560,Rm 31-70, Ft Detrick, MD 21702 USA. EM gameroa@ncifcrf.gov OI Maher, Stephen/0000-0003-0126-7906 NR 187 TC 97 Z9 100 U1 3 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2007 VL 14 IS 12 BP 1279 EP 1289 DI 10.2174/092986707780597907 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 158LZ UT WOS:000245794300001 PM 17504213 ER PT J AU Chen, W Perruche, S Li, J AF Chen, WanJun Perruche, Sylvain Li, Jun TI CD4(+)CD25(+) T regulatory cells and TGF-beta in mucosal immune system: The good and the bad SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE TGF-beta; CD4(+)CD25(+)Tregs; Foxp3; Th17; IL-6; mucosal system; oral tolerance; IBD; colon cancer; HIV ID GROWTH-FACTOR-BETA; CONTROL INTESTINAL INFLAMMATION; ORAL TOLERANCE; PERIPHERAL TOLERANCE; DENDRITIC CELLS; GASTROINTESTINAL-TRACT; MEDIATED SUPPRESSION; AUTOIMMUNE-DISEASES; HIV-INFECTION; CUTTING EDGE AB Three major mucosal systems exist in the body, the oral-gastrointestinal, the respiratory and the genitourinary systems. In particular, the gastrointestinal (GI) tract contains the largest mucosal surface in the body and is the major port of entry for foreign antigens. Therefore, the gut immune system has to differentiate to tolerate dietary antigens and expel infectious and harmful pathogens. During the complex but well-orchestrated immune responses in the mucosal system, T cells play a pivotal role in both immunity and tolerance. Of many T cell subpopulations, CD4(+)CD25(+) T regulatory cells (Tregs) are instrumental in regulation of immune responses in mucosea. Among the multitude of cytokines and factors that are produced in the gut, Transforming Growth Factor-beta (TGF-beta) is probably the most important one in influencing mucosal T cell responses. The interaction and mutual regulation between TGF-beta and CD4(+)CD25(+) Tregs may be the key in maintaining the balance between T cell immunity and tolerance in mucosal system. In this article, we attempt to discuss both beneficial and detrimental effects of TGF-beta and Tregs on oral tolerance, mucosal inflammation and autoimmunity, colon cancer and HIV infection in the gut. C1 NIDCR, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Chen, W (reprint author), NIDCR, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bldg 30,Room 304, Bethesda, MD 20892 USA. EM wchen@mail.nih.gov RI Li, Jun/N-6267-2015 FU Intramural NIH HHS NR 73 TC 23 Z9 28 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2007 VL 14 IS 21 BP 2245 EP 2249 DI 10.2174/092986707781696591 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 207CK UT WOS:000249229000003 PM 17896973 ER PT J AU Pappa, A Franco, R Schoneveld, O Galanis, A Sandaltzopoulos, R Panayiotidis, MI AF Pappa, A. Franco, R. Schoneveld, O. Galanis, A. Sandaltzopoulos, R. Panayiotidis, M. I. TI Sulfur-containing compounds in protecting against oxidant-mediated lung diseases SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE lung diseases; oxidants; antioxidants; oxidative stress; cellular toxicity; sulfur-containing compounds; sulfur metabolism; glutathione ID IDIOPATHIC PULMONARY FIBROSIS; BRONCHOALVEOLAR LAVAGE FLUID; OXYGEN RADICAL PRODUCTION; EPITHELIAL LINING FLUID; KAPPA-B ACTIVATION; N-ACETYLCYSTEINE; HYDROGEN-PEROXIDE; TAURINE CHLORAMINE; RAT LUNGS; ANTIOXIDANT DEFENSES AB Over 95% of the oxygen we metabolize undergoes a four-electron reduction to produce two molecules of water. Whenever electrons escape from the mitochondrial electron -transport chain and pass directly onto oxygen, oxidants that can cause cytotoxicity are generated. The lung being constantly exposed to atmospheric oxygen is more susceptible to oxidant-induced cellular damage. For instance, increased generation of oxidants is implicated in many pulmonary pathological conditions including emphysema, adult respiratory distress syndrome, idiopathic pulmonary fibrosis and asthma. Sulfur is an essential major inorganic element with a recently described protective cellular role. One of its many biologically important functions is the formation of disulfide bridges between two cysteine molecules thus stabilizing protein conformation. Also, it provides the site for attachment and transfer of 1-C methyl groups via formation of S-adenosylmethionine, and most importantly it is an essential constituent of the antioxidant tripeptide, glutathione, and vitamins like thiamin and biotin. However, its protective role emanates from its antioxidant properties in the context of sulfur-containing compounds (S-adenosylmethionine, cysteine, taurine, glutathione etc) that are known to act in protecting against oxidant-induced lung disease. The efficacy of these sulfur-containing compounds in scavenging oxidants directly or indirectly and consequently protecting against lung diseases is discussed herein. C1 Univ Nevada, Sch Publ Hlth, Dept Environm & Occupat Hlth, Reno, NV 89557 USA. Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis 68100, Greece. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Panayiotidis, MI (reprint author), Univ Nevada, Sch Publ Hlth, Dept Environm & Occupat Hlth, MS-274, Reno, NV 89557 USA. EM panagiotidism@yahoo.com RI Pappa, Aglaia/E-8663-2011; Franco, Rodrigo/D-9470-2013 OI Franco, Rodrigo/0000-0003-3241-8615 FU Intramural NIH HHS NR 70 TC 12 Z9 13 U1 2 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2007 VL 14 IS 24 BP 2590 EP 2596 DI 10.2174/092986707782023262 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 213MR UT WOS:000249672300008 PM 17979712 ER PT J AU Beghi, E Mennini, T Bendotti, C Bigini, P Logroscino, G Chio, A Hardiman, O Mitchell, D Swingler, R Traynor, BJ Al-Chalabi, A AF Beghi, Ettore Mennini, Tiziana Bendotti, Caterina Bigini, Paolo Logroscino, Giancarlo Chio, Adriano Hardiman, Orla Mitchell, Douglas Swingler, Robert Traynor, Bryan J. Al-Chalabi, Ammar TI The heterogeneity of amyotrophic lateral sclerosis: A possible explanation of treatment failure SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE amyotrophic lateral sclerosis; motor neuron disease; heterogeneity; epidemiology; biochemistry; genetics ID MOTOR-NEURON DISEASE; PLACEBO-CONTROLLED TRIAL; THYROTROPIN-RELEASING-HORMONE; CILIARY NEUROTROPHIC FACTOR; SUPEROXIDE-DISMUTASE GENE; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-I; PREDICTS SURVIVAL-TIME; TRANSGENIC MOUSE MODEL; TUMOR-NECROSIS-FACTOR AB Amyotrophic lateral sclerosis (ALS) is a severe clinical condition characterized by upper and lower motor neuron degeneration for which there is no truly effective treatment. The absence of an effective treatment can be explained in part by the complex and heterogeneous genetic, biochemical, and clinical features of ALS. While ALS accounts for the majority of the motor neuron diseases, the recognition of disease variants and mimic syndromes may lead to further insights into possible causes for the generality of ALS. From a biochemical perspective, the process of motor neuron degeneration is complex and the multifactorial influences and potential biomarkers of ALS have never been assessed in the light of the clinical heterogeneity of ALS. Several genes and environmental influences have been suggested as possible risk factors of ALS. A better understanding of interactions between these risk factors, potential biomarkers and heterogeneous clinical features may lead to more clearly defined pathological profiles among individuals or groups of ALS patients and in turn lead to more focused therapeutic trials. C1 [Beghi, Ettore; Mennini, Tiziana; Bendotti, Caterina; Bigini, Paolo] Ist Ric Farmacol Mario Negri, I-20156 Milan, Italy. [Logroscino, Giancarlo] Harvard Univ, Dept Epidemiol HSPH, Boston, MA 02115 USA. [Chio, Adriano] Univ Turin, Dept Neurosci, I-10124 Turin, Italy. [Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [Hardiman, Orla] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Mitchell, Douglas] Royal Preston Hosp, Preston MND Care & Res Ctr, Preston, Lancs, England. [Swingler, Robert] Ninewells Hosp & Med Sch, Dept Neurol, Dundee, Scotland. [Traynor, Bryan J.] NIH, NIMH, Sect Dev Genet Epidemiol, Bethesda, MD USA. [Al-Chalabi, Ammar] Kings Coll London, MRC Ctr Neurodegenerat Res, London WC2R 2LS, England. RP Beghi, E (reprint author), Ist Ric Farmacol Mario Negri, Via Masa 19, I-20156 Milan, Italy. EM beghi@marionegri.it RI Al-Chalabi, Ammar/E-5361-2010; Traynor, Bryan/G-5690-2010; LOGROSCINO, GIANCARLO/K-5148-2016; OI Al-Chalabi, Ammar/0000-0002-4924-7712; LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chio, Adriano/0000-0001-9579-5341 NR 321 TC 34 Z9 34 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2007 VL 14 IS 30 BP 3185 EP 3200 DI 10.2174/092986707782793862 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 268KS UT WOS:000253579300005 PM 18220753 ER PT J AU Martins, JL Keim, CN Farina, M Kachar, B Lins, U AF Martins, Juliana Lopes Keim, Carolina Neumann Farina, Marcos Kachar, Bechara Lins, Ulysses TI Deep-etching electron microscopy of cells of Magnetospirillum magnetotacticum: Evidence for filamentous structures connecting the magnetosome chain to the cell surface SO CURRENT MICROBIOLOGY LA English DT Article ID MAGNETITE; ULTRASTRUCTURE; MEMBRANE AB Magnetospirillum magnetotacticum are magnetotactic bacteria that form a single chain of magnetite magnetosomes within its cytoplasm. Here, we studied the ultrastructure of M. magnetotacticum by freeze-fracture and deep-etching to understand the spatial correlation between the magnetosome chain and the cell envelope and its possible implications for magnetotaxis. Magnetosomes were found mainly near the cell envelope, forming chains that were closely associated with the granular cytoplasmic material. The membrane surrounding the magnetosomes could be visualized in deep-etching preparations. Thin connections between magnetosome chains and the cell envelope were observed in deep-etching images. These results strengthen the hypothesis for the existence of structures that transfer the torque from the magnetosome chains to the whole cell during the orientation of magnetotactic bacteria to a magnetic field lines. C1 Univ Fed Rio de Janeiro, CCS, Dept Microbiol Geral, Inst Microbiol Prof Paulo de Goes, BR-21941590 Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, CCS, Inst Ciencias Biomed, BR-21941590 Rio De Janeiro, Brazil. NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Lins, U (reprint author), Univ Fed Rio de Janeiro, CCS, Dept Microbiol Geral, Inst Microbiol Prof Paulo de Goes, Bloco 1, BR-21941590 Rio De Janeiro, Brazil. EM ulins@micro.ufrj.br RI Keim, Carolina/E-3658-2013; Farina, Marcos/I-3744-2014; Lins, Ulysses/N-7282-2015 OI Keim, Carolina/0000-0002-3208-4128; Lins, Ulysses/0000-0002-1786-1144 NR 12 TC 16 Z9 17 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD JAN PY 2007 VL 54 IS 1 BP 1 EP 4 DI 10.1007/s00284-005-0221-9 PG 4 WC Microbiology SC Microbiology GA 118UU UT WOS:000242969100001 PM 17171472 ER PT J AU Fukuda, T Roberts, A Plotz, PH Raben, N AF Fukuda, Tokiko Roberts, Ashley Plotz, Paul H. Raben, Nina TI Acid alpha-glucosidase deficiency (Pompe disease) SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review ID ENZYME REPLACEMENT THERAPY; DRIED BLOOD SPOTS; LYSOSOMAL STORAGE DISORDERS; MALTASE DEFICIENCY; NATURAL COURSE; MORPHOLOGICAL-CHANGES; FOLLOW-UP; GLYCOGEN; MUSCLE; RECOMBINANT AB The development and recent approval of recombinant acid alpha-glucosidase for enzyme replacement therapy have been major milestones in Pompe disease research. Acid alpha-glucosidase is the enzyme responsible for degradation of glycogen polymers to glucose in the acidic milieu of the lysosomes. Cardiac and skeletal muscles are the two major tissues affected by the accumulation of glycogen within the lysosomes. Both cardiomyopathy and skeletal muscle myopathy are observed in patients with complete enzyme deficiency; this form of the disease is fatal within the first year of life. Skeletal muscle myopathy eventually leading to respiratory insufficiency is the predominant manifestation of partial enzyme deficiency. The recombinant enzyme alglucosidase alfa is the first drug ever approved for this devastating disorder. This review discusses the benefits and the shortcomings of the new therapy. C1 [Fukuda, Tokiko; Roberts, Ashley; Plotz, Paul H.; Raben, Nina] NIAMSD, Arthritis & Rheumatism Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Raben, N (reprint author), NIAMSD, Arthritis & Rheumatism Branch, NIH, Ctr Clin, 9000 Rockville Pike,Bldg 10-9N244, Bethesda, MD 20892 USA. EM rabenn@mail.nih.gov NR 55 TC 24 Z9 26 U1 1 U2 9 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD JAN PY 2007 VL 7 IS 1 BP 71 EP 77 DI 10.1007/s11910-007-0024-4 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 279RC UT WOS:000254371300009 PM 17217857 ER PT J AU Kalueff, AV Tuohimaa, P AF Kalueff, Allan V. Tuohimaa, Pentti TI Neurosteroid hormone vitamin D and its utility in clinical nutrition SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Review DE neurosteroid hormone; supplementation and therapy; vitamin D ID D-RECEPTOR GENE; CHEMICALLY-INDUCED SEIZURES; KLOTHO MUTANT MICE; MULTIPLE-SCLEROSIS; D DEFICIENCY; BRAIN-DEVELOPMENT; RAT-BRAIN; 1,25-DIHYDROXYVITAMIN D-3; CEREBRAL-CORTEX; KNOCKOUT MICE AB Purpose of review Vitamin D is a seco-steroid hormone with multiple functions in the nervous system. We discuss clinical and experimental evidence of the role of vitamin D in normal and pathological brain functions, and analyze the relative importance of vitamin D-modulated brain mechanisms at different stages of life. We also outline perspectives for the use of vitamin D in clinical nutrition to prevent or treat various brain disorders. Recent findings Numerous brain dysfunctions are linked to vitamin D deficits and/or dysfunctions of its receptors. In both animals and humans, vitamin D serves as an important endogenous and/or exogenous regulator of neuroprotection, antiepileptic and anticalcification effects, neuro-immunomodulation, interplay with neurotransmitters and hormones, modulation of behaviors, brain ageing, and some other, less-explored, brain processes. Summary Vitamin D emerges as an important neurosteroid hormone in the brain, with a strong potential for age-specific applications in clinical nutrition. C1 Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Clin Chem, FIN-33521 Tampere, Finland. RP Kalueff, AV (reprint author), NIH, Bld 10,Rm 3D41, Bethesda, MD 20892 USA. EM avkalueff@inbox.ru NR 104 TC 117 Z9 120 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD JAN PY 2007 VL 10 IS 1 BP 12 EP 19 DI 10.1097/MCO.0b013e328010ca18 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 125SJ UT WOS:000243462400003 PM 17143049 ER PT J AU Malech, HL Hickstein, DD AF Malech, Harry L. Hickstein, Dennis D. TI Genetics, biology and clinical management of myeloid cell primary immune deficiencies: chronic granulomatous disease and leukocyte adhesion deficiency SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE allogeneic transplantation; chronic granulomatous disease; gene therapy; hematopoietic stem cell; leukocyte adhesion deficiency; phagocytic cells ID BONE-MARROW-TRANSPLANTATION; GDP-FUCOSE TRANSPORTER; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; NADPH OXIDASE; HEMATOPOIETIC ALLOGRAFT; CYBB GENE; THERAPY; MUTATIONS; INFECTION; NEUTROPHIL AB Purpose of review Chronic granulomatous disease and leukocyte adhesion deficiency are the major primary immune deficiencies affecting phagocytic blood cells. Major advances in clinical diagnosis and development of novel treatments for these disorders merit review. Recent findings Clinically beneficial gene therapy correction of X-linked chronic granulomatous disease in two adult patients was reported. Nonmyeloablative busulfan conditioning before administration of gene corrected autologous hematopoietic stem cells was likely an essential maneuver to achieve successful gene therapy. There is an increased association of autoimmune disorders with chronic granulomatous disease. Preimplantation genetic diagnosis of leukocyte adhesion deficiency-I led to the birth of a normal child. A canine model of leukocyte adhesion deficiency-I facilitated development of new nonmyeloablative hematopoietic stem cell transplant and gene therapy approaches to leukocyte adhesion deficiency. Nonmyeloablative transplantation may provide an effective, but less toxic approach for leukocyte adhesion deficiency in children. There have been advances in understanding the basis of leukocyte adhesion deficiency-II and III. Summary The most important subjects reviewed in this chapter include new advances in development of gene therapy for chronic granulomatous disease and leukocyte adhesion deficiency-I; transplantation for leukocyte adhesion deficiency-I prenatal diagnosis of leukocyte adhesion deficiency-I; and association of autoimmune diseases with chronic granulomatous disease. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20982 USA. NCI, Expt Transplantat & Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Malech, HL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 5-3750,10 Ctr Dr,MSC 1456, Bethesda, MD 20982 USA. EM hmalech@nih.gov NR 69 TC 49 Z9 52 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2007 VL 14 IS 1 BP 29 EP 36 DI 10.1097/00062752-200701000-00007 PG 8 WC Hematology SC Hematology GA 118SH UT WOS:000242961500006 PM 17133097 ER PT J AU Motumi, N Emery, S Lane, HC AF Motumi, Ntsiki Emery, Sean Lane, H. Clifford TI Project Phidisa: development of clinical research capacity within the South African National Defence Force SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE AIDS; clinical; HIV; medicine; military; research AB In December 2002, a decision was reached between the South African Military Health Service of the South African National Defence Force and the US Ambassador to South Africa that the USA and the Republic of South Africa would explore the possibility of initiating a collaborative effort to build the capacity to conduct clinical research within the South African military environment and that the area of initial focus would be HIV/AIDS. Three and a half years later, a clinical research program now known as Project Phidisa has enrolled over 4000 patients on Institutional Review Board-approved protocols, and provided antiretroviral therapy to approximately 1400 members of the South African National Defence Force and their dependents. The purpose of this article is to present some of the challenges faced in the development of this program and provide the lessons learned as these challenges were and continue to be addressed. C1 [Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Emery, Sean] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. RP Lane, HC (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike,10 Ctr Dr MSC 1876,Bldg 10,Ro, Bethesda, MD 20892 USA. EM CLane@niaid.nih.gov NR 3 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2007 VL 2 IS 1 BP 69 EP 76 DI 10.1097/COH.0b013e328011e9c0 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NR UT WOS:000208417600011 PM 19372868 ER PT J AU Boikos, SA Stratakis, CA AF Boikos, Sosipatros A. Stratakis, Constantine A. TI Carney complex: the first 20 years SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE acromegaly; adrenal hyperplasia; Cushing syndrome; multiple endocrine neoplasias; pituitary tumors; PRKAR1A ID PROTEIN-KINASE-A; SPOTTY SKIN PIGMENTATION; PEUTZ-JEGHERS-SYNDROME; SUBUNIT TYPE 1A; REGULATORY SUBUNIT; ENDOCRINE OVERACTIVITY; MOLECULAR-GENETICS; BINDING-PROTEINS; I-ALPHA; TUMORS AB Purpose of review The purpose of this review is to comment on the current findings on Carney complex, a dominantly inherited disease and a unique multiple endocrine neoplasia syndrome. Recent findings Sequencing of the PRKAR1A gene in more than 150 kindreds has revealed a number of pathogenic mutations; in more than 90% of the cases, the sequence change was predicted to lead to a premature stop codon and, thus, mutant mRNAs were subject to nonsense-mediated mRNA decay. In Carney complex syndrome cells carrying these mutations, protein kinase A activity is irregularly stimulated by cAMP. Mutations that did not lead to a premature stop codon have also been described; these were also associated with abnormal protein kinase A activity. Animal models of the disease have been recently developed; they reproduced some of the stigmata of Carney complex syndrome but not all. Genetic testing of patients' family members has been introduced in recent years, leading to early detection and a better overall prognosis. Summary New treatments have yet to be applied; the elucidation of the molecular pathways regulated by PRKAR1A holds the promise of leading to molecularly designed therapies. C1 NICHD, Sect Endocrinol & Genet, DEB, NIH, Bethesda, MD 20892 USA. RP Boikos, SA (reprint author), NICHD, Sect Endocrinol & Genet, DEB, NIH, Bldg 10,CRC,Room I-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 39 TC 77 Z9 80 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JAN PY 2007 VL 19 IS 1 BP 24 EP 29 DI 10.1097/CCO.0b013e32801195eb PG 6 WC Oncology SC Oncology GA 119ZW UT WOS:000243054000005 PM 17133108 ER PT J AU Kiley, J Smith, R Noel, P AF Kiley, James Smith, Robert Noel, Patricia TI Asthma phenotypes SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article DE allergic asthma; aspirin-sensitive asthma; asthma therapy; genotypes; phenotypes; steroid resistant asthma ID ASPIRIN-INTOLERANT ASTHMA; ENVIRONMENT INTERACTION; LUNG-FUNCTION; TNF-ALPHA; ADAM33; GENE; POLYMORPHISMS; ASSOCIATION; PREDICT; LIFE AB Purpose of review Asthma is a heterogeneous disorder presenting with many phenotypes. Precise phenotypic definition has eluded the medical research community for years, despite recognition of different disease subtypes. Improved phenotypic characterization and knowledge of underlying pathobiology 1 is necessary for linkage of specific genotypes with clinical disease manifestations. Recent findings Phenotyping has been difficult because asthma is likely to be comprised of overlapping syndromes with varying origins and heterogeneous pathobiology. Currently, the field is too reliant on classification by trigger or symptoms. Since genotypic and phenotypic heterogeneity are inherent in asthma, patients presenting with different asthma phenotypes may need tailored therapies. Studies have begun to link genetics with disease mechanism and therapeutic response. As disease etiology, onset, progression and severity vary greatly among patients, however, the relative contribution of genetic factors may be difficult to ascertain. Definition of the full array of complex biological consequences of molecular target modulation is a prerequisite for therapies based on this concept. Summary The advent of targeted therapies for asthma and clinical trials based on phenotype and genotype have raised interest in more accurate description of asthma phenotypes. Therapies based on phenotypic and genotypic characteristics may be useful in asthma management. A variety of factors, however, must be addressed before such approaches become standard. C1 NHLBI, Div Lung Dis, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Kiley, J (reprint author), NHLBI, Div Lung Dis, US Dept HHS, NIH, 6701 Rockledge Dr,Room 10018, Bethesda, MD 20892 USA. EM kileyj@nhlbi.nih.gov NR 41 TC 42 Z9 46 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD JAN PY 2007 VL 13 IS 1 BP 19 EP 23 PG 5 WC Respiratory System SC Respiratory System GA 119ZV UT WOS:000243053900004 PM 17133120 ER PT J AU Zhang, MY Dimitrov, DS AF Zhang, Mei-Yun Dimitrov, Dimiter S. TI Novel approaches for identification of broadly cross-reactive HIV-1 neutralizing human monoclonal antibodies and improvement of their potency SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE antibodies; HIV; AIDS; vaccines; inhibitors; gp120; gp41 ID HUMAN-IMMUNODEFICIENCY-VIRUS; CORECEPTOR BINDING-SITE; ENVELOPE GLYCOPROTEINS; ENTRY INHIBITORS; GP41 EPITOPE; CELL-LINES; TYPE-1; GP120; CD4; INFECTION AB Human monoclonal antibodies (hmAbs) that neutralize HIV isolates from different clades at physiologically relevant concentrations (broadly cross-reactive neutralizing antibodies (bcnAbs)) are rare in infected individuals. Only small number of such antibodies have been identified and extensively characterized, but efforts to elicit them in vivo have not been Successful. We have recently developed novel approaches, based on sequential (SAP) and competitive (CAP) antigen panning methodologies, and the use of antigens with increased exposure of conserved epitopes, for enhanced identification of bcnAbs to gp 120-gp41. Some of the antibodies identified by using these approaches (X5, m6, rn9) bind better to gp120-CD4 complexes than to gp120 alone (CD4i antibodies); they exhibit exceptional neutralizing activity and breadth of neutralization as scFvs and on average lower potency as Fabs and IgGs. Other antibodies that compete with CD4 for binding to gp120 (m14, m 18) (CD4bs antibodies) are weaker neutralizers but also exhibit broad neutralizing activity although at relatively high concentrations. The anti-gp41 antibodies (m43, m44, m45, m47 and m48) appear to have broad cross-reactivity and bind to a new group of conserved conformational epitopes distinct from those of the bcnAbs 4E 10, 2F5 and Z 13. Recently, the crystal structures of X5, in 14 and m 18 have been solved and compared to those of 17b and b 12; they all contain long H3s that play a major role in their mechanism of binding. The H3s of X5, m6 and rn9, unlike the others known, appear to be very flexible which may be related to the mechanism of their exceptional neutralizing activity. The further characterization of the molecular interactions of the bcnAbs with gp120-gp41 will undoubtedly help in our understanding of the mechanisms of virus neutralization, and in the design of entry inhibitors and vaccines. C1 NCI, CCRNP, CCR, NIH,Prot Interact Grp, Frederick, MD 21702 USA. NCI, BRP, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Zhang, MY (reprint author), NCI, CCRNP, CCR, NIH,Prot Interact Grp, Bldg 469,Rm 131,POB B,Miller Dr, Frederick, MD 21702 USA. EM zhangm@ncifcrf.gov; dimitrov@ucifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 62 TC 15 Z9 17 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 2 BP 203 EP 212 DI 10.2174/138161207779313669 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 135QH UT WOS:000244167600007 PM 17269928 ER PT J AU Phogat, S Wyatt, R AF Phogat, S. Wyatt, R. TI Rational modifications of HIV-1 envelope glycoproteins for immunogen design SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE HIV vaccine; envelope glycoproteins; structure-assisted immunogen design ID HUMAN-IMMUNODEFICIENCY-VIRUS; CORECEPTOR-BINDING-SITE; 2ND HYPERVARIABLE REGION; NEUTRALIZING ANTIBODIES; VACCINE DESIGN; TYPE-1 GLYCOPROTEIN; RECEPTOR-BINDING; PARTIAL DELETION; PRIMARY ISOLATE; OLIGOMERIC STRUCTURE AB An effective vaccine against the human immunodeficiency virus type 1 (HIV-1) will likely require the elicitation of broadly neutralizing antibodies as well as cellular responses. The HIV exterior envelope glycoprotein trimers, gp 120, and the transmembrane glycoprotein, gp41, mediate entry and are the sole viral targets for neutralizing antibodies. However, as subunit immunogens the envelope glycoproteins do not efficiently elicit antibodies capable of neutralizing the extremely diverse array of viruses circulating in the human population. The preponderance of data suggest that inefficient generation of broadly neutralizing antibodies is due to naturally evolved mechanisms of immune evasion inherent in the unmodified HIV envelope glycoproteins. Because the established modes of anti-viral vaccine development, live-attenuation and virus inactivation have not yet been successful for HIV, we and others have focused on subunit vaccine design. In this review, we describe current approaches of rational modification of the envelope glycoproteins based upon structure, antigenicity, biochemistry and biophysics to alter the properties of the envelope glycoproteins such that, as subunit immunogens, they now better elicit broadly neutralizing antibodies. The application of structure-assisted, rational subunit vaccine design may be a general paradigm for future efforts to develop vaccines against emerging human pathogens. C1 NIAID, Struct Virol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Wyatt, R (reprint author), NIAID, Struct Virol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 4512, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov FU Intramural NIH HHS NR 106 TC 70 Z9 70 U1 1 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 2 BP 213 EP 227 DI 10.2174/138161207779313632 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 135QH UT WOS:000244167600008 PM 17269929 ER PT J AU Monti, S Proietti-Pannunzi, L Sciarra, A Lolli, F Falasca, P Poggi, M Celi, FS Toscano, V AF Monti, S. Proietti-Pannunzi, L. Sciarra, A. Lolli, F. Falasca, P. Poggi, M. Celi, F. S. Toscano, V. TI The IGF axis in prostate cancer SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-2; SIMIAN-VIRUS-40 T-ANTIGEN; EPITHELIAL-CELLS; ELEVATED LEVELS; FACTOR RECEPTOR; STROMAL CELLS; FACTOR SYSTEM; GENE-EXPRESSION; FACTOR (IGF)-I AB Prostate cancer, the most frequent non-cutaneous malignancy in men from industrialized countries, is a growing medical problem, representing the second leading cause of male cancer deaths. In the last decade, converging evidence from epidemiological and biological studies suggests that the Insulin-like Growth Factor (IGF) axis is involved in the tumorigenesis and neoplastic growth of prostate cancer. Epidemiological observations indicated that circulating IGF-I levels are positively associated with the increased risk of prostate cancer. The activation of type I IGF receptor (IGF-IR) by IGF-I and/or IGF-II, has mitogenic and antiapoptotic effects on normal and malignant prostate cells. Altered expression of IGF axis components has also been reported in vitro and in animal models of prostate cancer, as well as in human prostate cancer tissue samples. In this review we address and analyze epidemiological studies, in vitro and in vivo cancer models, and human ex vivo prostate cancer researches performed to date supporting the role of IGF axis in prostate cancer. C1 Azienda Osped St Andrea, UOC Endocrinol, I-00198 Rome, Italy. Univ Roma La Sapienza, Dipartimento Fisiopatol Med, Rome, Italy. Univ Roma La Sapienza, Dipartimento Urol U Bracci, Rome, Italy. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Monti, S (reprint author), Azienda Osped St Andrea, UOC Endocrinol, Via Grottarossa 1035-1039, I-00198 Rome, Italy. EM salvatore.monti@uniroma1.it OI Sciarra, Alessandro/0000-0002-7899-8056 FU Intramural NIH HHS NR 78 TC 25 Z9 28 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 7 BP 719 EP 727 DI 10.2174/138161207780249128 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 165UO UT WOS:000246331600006 PM 17346186 ER PT J AU Hill, JM AF Hill, Joanna M. TI Vasoactive intestinal peptide in neurodevelopmental disorders: Therapeutic potential SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE embryogenesis; autism; Down syndrome; fetal alcohol syndrome ID DEPENDENT NEUROTROPHIC FACTOR; FETAL ALCOHOL SYNDROME; CYCLASE-ACTIVATING POLYPEPTIDE; CULTURED MOUSE EMBRYOS; GTP-INSENSITIVE FORM; EYE-MOVEMENT SLEEP; DOWN-SYNDROME; AUTISTIC DISORDER; MESSENGER-RNA; GROWTH-FACTOR AB Vasoactive intestinal peptide (VIP) mediates important events during the development of the nervous system. VIP can stimulate neuronogenesis as well as differentiation and neurite outgrowth; it can promote the survival of neurons and assist in neuronal repair; it is also anti-inflammatory and can modulate immune responses. In addition, VIP is necessary for the normal growth and development of the early postimplantation mouse embryo during the period when the major embryonic events are neural tube formation, neuronogenesis and expansion of the vascular system. Receptors for VIP appear during early postimplantation embryogenesis in the rodent and exhibit changing localization patterns throughout the development of the brain. During embryogenesis, unregulated VIP may have major and permanent consequences on the formation of the brain and may be a participating factor in disorders of neurodevelopment. VIP has been linked to autism, Down syndrome and fetal alcohol syndrome. This paper will review the role of VIP in neurodevelopment, its known involvement in neurodevelopmental disorders and propose ways in which VIP might be of therapeutic value. C1 NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. RP Hill, JM (reprint author), NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. EM hilljoa@mail.nih.gov NR 162 TC 22 Z9 25 U1 2 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 11 BP 1079 EP 1089 DI 10.2174/138161207780618975 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 170QU UT WOS:000246679900002 PM 17430171 ER PT J AU Busciglio, J Pelsman, A Helguera, P Ashur-Fabian, O Pinhasov, A Brenneman, DE Gozes, I AF Busciglio, Jorge Pelsman, Alciandra Helguera, Pablo Ashur-Fabian, Osnat Pinhasov, Albert Brenneman, Douglas E. Gozes, Illana TI NAP and ADNF-9 protect normal and Down's syndrome cortical neurons from oxidative damage and apoptosis SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID VASOACTIVE-INTESTINAL-PEPTIDE; DEPENDENT NEUROTROPHIC FACTOR; CYCLASE-ACTIVATING POLYPEPTIDE; ACTING NEUROPROTECTIVE PEPTIDE; MOUSE MODEL; HEAD-INJURY; ALZHEIMERS-DISEASE; AMYLOID-BETA; WATER MAZE; VIP AB NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gin, single letter code: NAPVSIPQ) and ADNF-9 (activity-dependent neurotrophic factor-9; Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala; single letter code: SALLRSIPA) are peptides derived from naturally occurring glial proteins that have shown neuroprotection in rodent model systems. Here, the neuroprotective activity of ADNF-9 and NAP was tested in two human models of neuronal degeneration in culture mediated by oxidative stress: normal human cortical neurons treated with H2O2 and Down's syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 mu M H2O2 for 1 hour resulted in morphological and structural changes consistent with neuronal degeneration and loss of viability of more than 60% of the neurons present in the culture. Addition of ADNF-9 or NAP at femtomolar concentrations resulted in significant increases in survival of normal neurons treated with H2O2. Femtomolar concentrations of ADNF-9 or NAP exhibited a similar neuroprotective efficacy, comparable to the antioxidant N-tert-butyl-2-sulpho-phenylnitrone at 100 mu M (s-PBN). Treatment of DS cortical neurons with ADNF-9 or NAP resulted in a significant increase in neuronal survival as well as reduction of degenerative morphological changes. The results suggest that ADNF-9 and NAP possess potent neuroprotective properties against oxidative damage in human neurons that may be useful to preserve neuronal function and prevent neuronal death associated with chronic neurodegenerative disorders. C1 Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. Tel Aviv Univ, Dept Human Mol Genet & Biochem, Sacler Fac Med, IL-69978 Tel Aviv, Israel. NICHHD, Sect Dev & Mol Pharmacol, Lab Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP Busciglio, J (reprint author), Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. EM jbuscigl@uci.edu; igozes@post.tau.ac.il FU NICHD NIH HHS [HD38466] NR 70 TC 35 Z9 35 U1 4 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 11 BP 1091 EP 1098 DI 10.2174/138161207780618957 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 170QU UT WOS:000246679900003 PM 17430172 ER PT J AU Moody, TW Gozes, I AF Moody, Terry W. Gozes, Illana TI Vasoactive intestinal peptide receptors: A molecular target in breast and lung cancer SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE VIP; PACAP; receptors; breast cancer; lung cancer ID CYCLASE-ACTIVATING POLYPEPTIDE; CARCINOMA CELL-LINES; ADENYLATE-CYCLASE; SIGNAL-TRANSDUCTION; PACAP RECEPTOR; VIP RECEPTORS; HIGH-AFFINITY; FUNCTIONAL EXPRESSION; BIOLOGICAL-ACTIVITY; SPLICE VARIANTS AB Vasoactive intestinal peptide (VIP) receptors are present in the normal brain as well as periphery, and cancer cells. Three major types of VIP receptors include the VPAC(1), VPAC(2) and PAC(1) receptors. VPAC(1) receptors are present in high densities on human lung and breast cancer cells lines and biopsy specimens. Radiolabeled VIP analogues have been developed for imaging of lung and breast cancer. Synthetic VIP receptor antagonists inhibit the proliferation and potentiate the ability of chemotherapeutic agents to cause apoptosis of lung and breast cancer cells. VIP-chemotherapeutic conjugates have been synthesized which bind to VPAC(1) receptors and are internalized, resulting in the killing of lung and breast cancer cells. These results suggest that VPAC(1) receptors may be molecular targets for diagnosis, prevention and treatment of breast cancer as well as lung cancer. C1 CCR, NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Moody, TW (reprint author), CCR, NCI, Dept Hlth & Human Serv, NIH, Bldg 31,Rm 4A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov NR 68 TC 22 Z9 22 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 11 BP 1099 EP 1104 DI 10.2174/138161207780619000 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 170QU UT WOS:000246679900004 PM 17430173 ER PT J AU Kesisis, G Broxterman, H Giaccone, G AF Kesisis, Georgios Broxterman, Henk Giaccone, Giuseppe TI Angiogenesis inhibitors. Drug selectivity and target specificity SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; MATRIX-METALLOPROTEINASE INHIBITOR; PHASE-I TRIAL; CELL LUNG-CANCER; COMBRETASTATIN A-4 PHOSPHATE; METASTATIC COLORECTAL-CANCER; 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID DMXAA; RECOMBINANT HUMAN ENDOSTATIN; SIGNAL-TRANSDUCTION PATHWAY; ADVANCED PANCREATIC-CANCER AB The critical role of angiogenesis in tumor development and progression has long been appreciated. The elucidation of the mechanisms of tumor angiogenesis and the emergence of anticancer drugs targeting the tumor vasculature has been a breakthrough in the treatment of several tumors in the last few years. Several novel molecules are being developed that target different aspects of angiogenesis. This review outlines the principle of anti-angiogenic therapies, illustrates the main mechanisms and complexity of growth signals involved in tumor angiogenesis, its interactions with hypoxia, stroma and tumor microenvironment. It provides a comprehensive review of clinical results obtained with anti-angiogenic agents (VEGF/VEGFR signaling inhibitors, direct angiogenesis inhibitors, vascular disrupting agents) and finally discusses the differences of the several approaches and their limitations due to the emergence of resistance. C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. RP Giaccone, G (reprint author), Theagenion Anticanc Ctr, Dept Med Oncol, Thessaloniki, Greece. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 172 TC 30 Z9 30 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 27 BP 2795 EP 2809 DI 10.2174/138161207781757033 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 214VT UT WOS:000249767000006 PM 17897024 ER PT J AU Pazgier, M Li, X Lu, W Lubkowski, J AF Pazgier, Marzena Li, Xiangqun Lu, Wuyuan Lubkowski, Jacek TI Human defensins: synthesis and structural properties SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Human alpha-defensins; human beta-defensins; antibacterial activity; recombinat and chemical synthesis; innate and adaptive immunity; antimicrobial and chemomatic activity; defensin structures; structure; function relationship ID HUMAN BETA-DEFENSINS; HIGH-LEVEL EXPRESSION; HUMAN ALPHA-DEFENSINS; CATIONIC ANTIMICROBIAL PEPTIDES; HUMAN BETA-DEFENSIN-2 GENE; HUMAN NEUTROPHIL DEFENSINS; SOLUBLE FUSION EXPRESSION; MULTIPLE JOINED GENES; CELL-FREE SYSTEM; RHESUS-MACAQUE LEUKOCYTES AB Defensins are small, P-sheet-rich, cationic peptides found in many organisms. All defensins have amphiphilic properties, which are central for antimicrobial activities of the proteins. The human genome encodes many defensin-line molecules, of which 10 have been characterized. Molecules of all known human defensins are stabilized by three intramolecular disulfide bonds arranged in a conserved pattern. To date, studies of human defensins indicate that these proteins are involved in various biological processes associated primarily with defensive and regulatory responses to infections by pathological agents. A comprehensive understanding of the multiple roles played by defensins within the immune system is greatly increased by reviewing the results of detailed structural studies. Emerging structural data, derived by the X-ray crystallography and the NMR spectroscopy in solution combined with functional studies allow a rational understanding of the different activities of defensins and the mechanisms controlling these activities. Due to their well-established antimicrobial properties, defensins are also being investigated for their potential as therapeutics agents. Recently, increased effort has been focused on studies of the immunoregulatory properties of defensins, associated with their ability to bind and activate the G(i)-protein-coupled seven-transmembrane receptors. Comprehensive studies of defensins require development of simple, efficient, and inexpensive methods to generate these proteins and their derivatives in correctly folded form. This review highlights the current status of the sample generation methods, structural studies, and the structure-function relationships for human defensins. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA. RP Lubkowski, J (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM jacek@ncifcrf.gov RI Lu, Wuyuan/B-2268-2010; Pazgier, Marzena/B-7295-2012 NR 282 TC 40 Z9 43 U1 2 U2 16 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 30 BP 3096 EP 3118 DI 10.2174/138161207782110381 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 226EP UT WOS:000250570600006 PM 17979752 ER PT J AU Yang, D Liu, ZH Tewary, P Chen, Q De la Rosa, G Oppenheim, JJ AF Yang, De Liu, Zhen-Hua Tewary, Poonam Chen, Qian De la Rosa, Gonzalo Oppenheim, Joost J. TI Defensin participation in innate and adaptive immunity SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE defensin; antimicrobial; dendritic cell; chemoattraction; activation; immune response; aqjuvant ID MOUSE BETA-DEFENSIN; EOSINOPHIL-DERIVED NEUROTOXIN; HUMAN NEUTROPHIL DEFENSINS; CATIONIC ANTIMICROBIAL PEPTIDES; DENDRITIC CELL MATURATION; HUMAN INTESTINAL DEFENSIN; AIRWAY EPITHELIAL-CELLS; GROWTH-FACTOR RECEPTOR; HERPES-SIMPLEX-VIRUS; ANTHRAX LETHAL TOXIN AB Defensins are endogenous, small, cysteine-rich antimicrobial peptides that are produced by leukocytes and epithelial cells. Substantial evidence accumulated in recent years indicates that mammalian defensins are multifunctional and, by interacting with host cell receptor(s), participate in both the innate and adaptive antimicrobial immunity of the host, A better understanding of the function of defensins in immunity has implications for the development of potential clinical therapeutics for the treatment of infection or cancer. Here we will briefly outline the classification, genes, expression, and structure of mammalian defensins and focus on their roles in innate and adaptive immune response of the host. C1 NCI, Basic Res Program, SAIC Frederick Inc, Canc & Inflammat Program,Ctr Canc Res,Lab Mol Imm, Frederick, MD 21702 USA. RP Yang, D (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Canc & Inflammat Program,Ctr Canc Res,Lab Mol Imm, 1050 Boyles St, Frederick, MD 21702 USA. EM dyang@nciterf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 176 TC 73 Z9 85 U1 2 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 30 BP 3131 EP 3139 DI 10.2174/138161207782110453 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 226EP UT WOS:000250570600008 PM 17979754 ER PT J AU Woods, AS Wang, HYJ Jackson, SN AF Woods, Amina S. Wang, Hay-Yan J. Jackson, Shelley N. TI A snapshot of tissue glycerolipids SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID TANDEM MASS-SPECTROMETRY; SITU STRUCTURAL-CHARACTERIZATION; ELECTROSPRAY-IONIZATION; MALDI-MS/MS; PHOSPHOLIPIDS; LIPIDOMICS; PHOSPHATIDYLCHOLINE; SPHINGOMYELIN; TOF; PHOSPHATIDYLINOSITOL AB The lipid membrane is the portal to the cell and its first line of defense against the outside world. Its plasticity, diversity and powers of accommodation in a myriad of environments, mirrored by the varied make up of the cells it protects are unparalleled. Glycerophospholipids are one of its major components. In cell membranes the extracellular layer is mainly made up of positively charged glycolipids, while the intracellular one's main components are negatively charged. Advances in mass spectrometry have allowed the direct probing of tissues, and thus a direct approach to probing membranes make up was developed. Until recently most studies have focused on proteins. An overview of the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) for the direct analysis of phospholipids in various tissue is presented. Molecular ions corresponding to phosphatidylcholines, sphingomyelin, phosphatidylethanolamines, phosphatidylserines, phosphatidylinositols and sulfatides were mapped. C1 NIDA IRP, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 35 TC 12 Z9 12 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 32 BP 3344 EP 3356 DI 10.2174/138161207782360636 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 239VT UT WOS:000251547100013 PM 18045188 ER PT J AU Pennington, JD Jacobs, KM Sun, L Bar-Sela, G Mishra, M Gius, D AF Pennington, J. Daniel Jacobs, Kristi Muldoon Sun, Lunching Bar-Sela, Gil Mishra, Mark Gius, David TI Thioredoxin and thioredoxin reductase as redox-sensitive molecular targets for cancer therapy SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE molecular targets; redox signaling; anticancer drug resistance; thioredoxin ID NF-KAPPA-B; GLUTATHIONE-S-TRANSFERASE; TRANSCRIPTIONAL REGULATOR OXYR; DNA-BINDING ACTIVITY; OXIDATIVE-STRESS; IONIZING-RADIATION; HYDROGEN-PEROXIDE; ESCHERICHIA-COLI; CELL-LINES; HEAT-SHOCK AB Tumor cell proliferation, de-differentiation, and progression depend on a complex combination of altered intracellular processes including cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. Metabolites from these processes result in significant cellular oxidative stress that must be buffered to prevent permanent cell damage and cell death. Tumor cells depend on a complex set of respiratory pathways to generate the necessary energy as well as redox-sensitive pro-survival signaling pathways and factors to cope with and defend against the detrimental effects of oxidative stress. It has been hypothesized that redox-sensitive signaling factors such as thioredoxin reductase-1 (TR) and thioredoxin (TRX) may represent central pro-survival factors that would allow tumor cells to evade the damaging and potentially cytotoxic effects of endogenous and exogenous agents that induce oxidative stress. The overarching theme of this review is an extension of the hypothesis that tumor cells use these redox sensitive pro-survival signaling pathways/factors, which are up-regulated due to increased tumor cell respiration, to evade the cytotoxic effects of anticancer agents. These observations suggest that redox-sensitive signaling factors may be potential novel molecular targets for drug discovery. C1 [Pennington, J. Daniel; Jacobs, Kristi Muldoon; Sun, Lunching; Bar-Sela, Gil; Mishra, Mark; Gius, David] NIH, NCI, Ctr Canc Res, Radiat Oncol Sci Program,Radiat Oncol Branch,Mol, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NIH, NCI, Ctr Canc Res, Radiat Oncol Branch,Mol Radiat Oncol Sect, Bldg 10,Room 3B43,9000 Rockville Pike, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [DK51612]; PHS HHS [A82722] NR 99 TC 46 Z9 51 U1 1 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2007 VL 13 IS 33 BP 3368 EP 3377 DI 10.2174/138161207782360528 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 239VU UT WOS:000251547200003 PM 18045191 ER PT J AU Nieddu, E Pasa, S AF Nieddu, Erika Pasa, Stefania TI Interfering with protein-protein contact: Molecular interaction maps and peptide modulators SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE protein-protein interactions (PPIs); molecular interaction maps (MIMs); peptides; c-Myc ID VIRUS RIBONUCLEOTIDE REDUCTASE; CELL-CYCLE ARREST; C-MYC; ANTIVIRAL ACTIVITY; IN-VIVO; PEPTIDOMIMETIC INHIBITORS; GROWTH SUPPRESSION; GENOMIC TARGETS; TRANSCRIPTION; IDENTIFICATION AB Protein-protein interactions (PPIs) can be useful targets for different pathologies. In fact controlling a function or attempting to repair an anomaly often means interfering with the cross-talk among different proteins. In order to have a general view of these cross-talks, Molecular Interaction Maps (MIMs) are used, organizing the enormous available information that is added every day and trying to understand the most suitable and accurate targets for any specific cell alteration. In this paper the c-Myc protein is taken as an example to explain the use of a map. The discovery of a peptidomimetic antagonist of c-Myc, active against proliferation of cancer cell lines, is reported and a possible mechanism of action is explained. To interfere with a specific protein-protein contact, a good starting point can be to consider a protein entity. Because the interaction between two proteins is normally characterized by a wide zone of contact, relative large inhibitors could be more convenient in the first approaches. Therefore, peptides mimicking the interacting zone can be considered as potential leads in the rational design of effective molecules. Here different examples of peptides as protein-protein interaction inhibitors are reported. C1 Univ Genoa, Dept Pharmaceut Chem, I-16132 Genoa, Italy. Natl Canc Inst, Expt Oncol Lab, I-16132 Genoa, Italy. RP Nieddu, E (reprint author), Univ Genoa, Dept Pharmaceut Chem, I-16132 Genoa, Italy. EM erika.nieddu@unige.it; stefania.pasa@istge.it NR 70 TC 10 Z9 10 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2007 VL 7 IS 1 BP 21 EP 32 DI 10.2174/156802607779318271 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 131HT UT WOS:000243860400003 PM 17266594 ER PT J AU Thompson, PE Manganiello, V Degerman, E AF Thompson, Philip E. Manganiello, Vincent Degerman, Eva TI Re-discovering PDE3 inhibitors - New opportunities for a long neglected target SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; KM CAMP PHOSPHODIESTERASE; CHRONIC HEART-FAILURE; DEPENDENT PROTEIN-KINASE; SOLID-PHASE SYNTHESIS; AORTIC SMOOTH-MUSCLE; FAILING HUMAN HEARTS; AMP PHOSPHODIESTERASE; INSULIN-SECRETION; RAT ADIPOCYTES AB The PDE3 enzymes or "low Kin cGMP-inhibited phosphodiesterases" have long been established as important mediators of cellular physiology, and synthetic PDE3 inhibitors have been critical to the delineation of the enzymes' roles. Yet despite decades of progress on the biology of these enzymes, the medicinal chemistry landscape relating to PDE3 inhibitors has remained essentially unchanged since the mid 1990's. Up until then the field was at the cutting edge of drug design; without the tools of molecular and structural biology, molecules of high potency were being achieved using logical pharmacophore models and lead modification. Yet virtually all the impetus went out of this area on the back of failures at the clinic and PDE3 as a therapeutic target largely fell out of favour. A decade later and with the "new" technologies of structural and molecular biology breathing new life into PDE3 research in general, PDE3 inhibitors are sought for target validation in an array of therapeutic applications. In this review, we examine the current state of PDE3 research; firstly we summarize the structural and functional properties of PDE3 enzymes with particular attention to the heterogeneity within this class of enzymes which differ markedly in expression, localisation and means of regulation across various tissue types. It is the structural and functional complexity of the PDE3 enzymes that underpins the re-emergence of PDE3s roles as targets for drug design. We then took at past clinical evaluation of PDE3 inhibitors that occurred without that. information and which may have had a significant bearing on the outcome of those drug discovery efforts. Finally we look at current approaches to the design of PDE3 inhibitors which utilize that historic data but also incorporate new inputs from structural biology and combinatorial chemistry. C1 Monash Univ, Victorian Coll Pharm, Dept Med Chem, Parkville, Vic 3052, Australia. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Lund Univ, Ctr Biomed, Dept Cell & Mol Biol, SE-22184 Lund, Sweden. RP Thompson, PE (reprint author), Monash Univ, Victorian Coll Pharm, Dept Med Chem, Parkville, Vic 3052, Australia. EM phil.thompson@vcp.monash.edu.au RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Thompson, Philip/0000-0002-5910-7625 NR 148 TC 48 Z9 51 U1 0 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2007 VL 7 IS 4 BP 421 EP 436 DI 10.2174/156802607779941224 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 143EP UT WOS:000244703100010 PM 17305583 ER PT J AU Laughon, BE AF Laughon, Barbara E. TI New tuberculosis drugs in development SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Article; Proceedings Paper CT 229th National Meeting of the American-Chemical-Society (ACS) CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc (ACS), ACS, Div Cellulose & Renewable Mat, Akzo Nobel Function Chem, Arch Wood Protect Inc, Ciba Specialty Chem, Eastman Chem Co, ISK Biocides Inc, Janssen Pharmaceutica, Lonza Inc, Merichem Co, FWRC, Mississippi State Univ, Nisus Corp, Osmose Hold Inc, Pibro Tech Inc, US Borax, Rio Tinto Minerals, Sostram Corp, Viance LLC, Weyerhaeuser Co DE tuberculosis; mycobacterium; drug development; medicinal chemistry; public-private partnerships; antibiotics; multidrug resistance; latency; acquired immunodeficiency syndrome : complications; antitubercular agents ID OXAZOLIDINONE ANTIBACTERIAL AGENTS; COMBINATORIAL LEAD OPTIMIZATION; MYCOLIC ACID SYNTHESIS; IN-VITRO ACTIVITIES; NEW-YORK-CITY; MYCOBACTERIUM-TUBERCULOSIS; MULTIDRUG-RESISTANT; PYRROLE DERIVATIVES; ANTIMYCOBACTERIAL COMPOUNDS; BACTERIAL-INFECTIONS AB Over the past 50 years, no new drug classes have been introduced to treat tuberculosis. Tuberculosis (TB) kills nearly two million people a year mainly in the poorest communities in the developing world. It afflicts millions more. About one third of the world's population is silently infected with TB that may erupt into disease with increased age or suppression of the immune system. Nearly nine million new active cases develop every year. The World Health Organization (WHO) declared the disease a global emergency as long ago as 1993. Although huge efforts in public health control have reduced the disease burden within most established market economies, in Africa and Asia the epidemic continues to accelerate, particularly fueled by the HIV epidemic. Furthermore, resistance to the standard drugs isoniazid and rifampicin is increasing worldwide. Since the 1990s, mycobacteria have emerged with resistance patterns rendering all currently available antibiotics ineffectual. The pharmaceutical industry has mostly abandoned TB drug development due to perceived non-profitable consumer market and the diminishing number of companies engaged in anti-infective research. The public sector and infectious disease researchers have responded to advance fundamental science and to create new chemical entities as early drug candidates. With support from research funding agencies, philanthropic donors, and the STOP-TB Partnership, new chemical tools and new approaches to effectively implement TB control programs are evolving. Advanced preclinical development and strategies for Phase III clinical trials remain gap areas that will require additional engagement from all sectors. C1 NIAID, Div Aids, NIH,Dept Hlth & Human Serv, Complicat & Coinfect Res Branch,Therapeut Res Pro, Bethesda, MD 20892 USA. RP Laughon, BE (reprint author), NIAID, Div Aids, NIH,Dept Hlth & Human Serv, Complicat & Coinfect Res Branch,Therapeut Res Pro, 6700-B Rockledge Dr Room 5108, Bethesda, MD 20892 USA. EM BLaughon@niaid.nih.gov NR 90 TC 26 Z9 28 U1 3 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2007 VL 7 IS 5 BP 463 EP 473 DI 10.2174/156802607780059736 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 148KQ UT WOS:000245073800002 PM 17346192 ER PT J AU Keskin, O Gursoy, A Ma, B Nussinov, R AF Keskin, O. Gursoy, A. Ma, B. Nussinov, R. TI Towards drugs targeting multiple proteins in a systems biology approach SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID STRUCTURALLY CONSERVED RESIDUES; HOT-SPOTS; SMALL MOLECULES; BINDING-SITES; REVERSE-TRANSCRIPTASE; COMPUTATIONAL METHODS; DISCOVERY; DESIGN; INTERFACES; RECEPTOR AB Protein-protein interactions are increasingly becoming drug targets. This is understandable, since they are crucial at all levels of cellular expression and growth. In practice, targeting specific disease-related interactions has proven difficult, with success varying with specific complexes. Here, we take a Systems Biology approach to targeting protein-protein interactions. Below, we first briefly review drug discovery targeted at protein-protein interactions; we classify protein-protein complexes with respect to their types of interactions and their roles in cellular function and as being targets in drug design; we describe the properties of the interfaces as related to drug design, focusing on hot spots and surface cavities; and finally, in particular, we cast the interactions into the cellular network system, highlighting the challenge of partially targeting multiple interactions in the networks as compared to hitting a specific protein-protein interaction target. The challenge we now face is how to pick the targets and how to improve the efficiency of designed partially-specific multi-target drugs that would block parallel pathways in the network. C1 SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, Basic Res Program,NCI, Frederick, MD 21702 USA. Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey. Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, Basic Res Program,NCI, Bldg 469,Rm 151, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011; Gursoy, Attila/E-9565-2015 OI Ma, Buyong/0000-0002-7383-719X; Gursoy, Attila/0000-0002-2297-2113 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 58 TC 39 Z9 40 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2007 VL 7 IS 10 BP 943 EP 951 DI 10.2174/156802607780906690 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 186JA UT WOS:000247773800004 PM 17508925 ER PT J AU Ma, B Nussinov, R AF Ma, Buyong Nussinov, Ruth TI Trp/Met/Phe hot spots in protein-protein interactions: Potential targets in drug design SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE protein-protein interactions; hot spot; drug-design; protein binding site; amyloid ID P53 TUMOR-SUPPRESSOR; GP120 ENVELOPE GLYCOPROTEIN; AMYLOID FORMATION; CRYSTAL-STRUCTURE; BINDING-SITES; RESIDUES; AGGREGATION; PREDICTION; IDENTIFICATION; INTERFACES AB Protein-protein interactions are crucial to biological functions. Consequently, designing drugs to control protein-protein interactions is receiving increasing attention. Protein structures can associate in different ways. Analysis of the structures of protein-protein complexes using amino acid sequence order-independent multiple structural comparison algorithms, led us to conclude that the amino acids Trp, Met, and Phe are important for protein-protein interactions. Hence, in principle, drug design targeting the Trp/Met/Phe should modulate protein functions effectively. Several clusters of the Trp/Met/Phe residues are involved in the p53 protein-protein interactions. The best example in this regard is the Phe 19/Trp23 of p53, which binds to transcriptional factors and to the MDM2 protein. In the HIV related proteins, the Trp/Met/Phe residues have roles in the dimerization of the transcriptase (p51/p66) and in cell-fusion processes, including the gp120-CD4 interaction and the gp41 six-helix bundle formation. Trp/Met/Phe residues are preferred in 'normal' functional protein-protein interactions and they also appear to be exploited in amyloid formation, especially the phenylalanine. Comparison of binding propensity and amyloid formation preference reveals that apart from Lysine, Isoleucine is the least structurally conserved in protein binding sites and has a high propensity in sequences forming amyloids. Thus, this may suggest that nature tends to avoid lie conservation in protein-protein interaction to avoid amyloid formation. In this regards, Trp/Met/Phe as well as Ile may be targeted to modulate protein-protein interaction. C1 NCI, SAIC Federick Inc, Ctr Canc Res, Nanobiol Program,Basic Res Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, B (reprint author), NCI, SAIC Federick Inc, Ctr Canc Res, Nanobiol Program,Basic Res Program, Frederick, MD 21702 USA. EM mab@ncifcrf.gov; ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 44 TC 60 Z9 61 U1 0 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2007 VL 7 IS 10 BP 999 EP 1005 DI 10.2174/156802607780906717 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 186JA UT WOS:000247773800012 PM 17508933 ER PT J AU Berna, MJ Jensen, RT AF Berna, Marc J. Jensen, Robert T. TI Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; IRRITABLE-BOWEL-SYNDROME; LOWER ESOPHAGEAL SPHINCTER; CHOLECYSTOKININ-B/GASTRIN RECEPTOR; ENTEROCHROMAFFIN-LIKE-CELL; PANCREATIC ACINAR-CELLS; CCK-A RECEPTOR; DUODENAL-ULCER DISEASE; GALLBLADDER EJECTION FRACTION; MEDULLARY-THYROID CARCINOMA AB Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes Of Health, Bethesda, Maryland In this paper, the estabished and possible roles of CCK1 and CCK2 receptors in gastrointestinal (GI) and metabolic diseases are reviewed and available results from human agonist/antagonist studies are discussed. While there is evidence for the involvement of CCK1R in numerous diseases including pancreatic disorders, motility disorders, tumor growth, regulation of satiety and a number of CCK-deficient states, the role of CCK1R in these conditions is not clearly defined. There are encouraging data from several clinical studies of CCK1R antagonists in some of these conditions, but their role as therapeutic agents remains unclear. The role of CCK2R in physiological (atrophic gastritis, pernicious anemia) and pathological (Zollinger-Ellison syndrome) hypergastrinemic states, its effects on the gastric mucosa (ECL cell hyperplasia, carcinoids, parietal cell mass) and its role in acid-peptic disorders are clearly defined. Furthermore, recent studies point to a possible role for CCK2R in a number of GI malignancies. Current data from human studies of CCK2R antagonists are presented and their potential role in the treatment of these conditions reviewed. Furthermore, the role of CCK2 receptors as targets for medical imaging is discussed. C1 NIDDK, DDB, NIH, Bethesda, MD 20892 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 FU Intramural NIH HHS [Z01 DK053100-19, Z01 DK053101-19] NR 375 TC 29 Z9 31 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2007 VL 7 IS 12 BP 1211 EP 1231 PG 21 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 197PR UT WOS:000248568500008 PM 17584143 ER PT J AU Cachau, RE Gonzalez-Nilo, FD Ventura, ON Fritts, MJ AF Cachau, Raul E. Gonzalez-Nilo, Fernando D. Ventura, Oscar N. Fritts, Martin J. TI In-silico nanobio-design. A new frontier in computational biology SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID SENSITIVITY ANALYSIS; DENDRIMERS; NANOTECHNOLOGY; SIMULATION; PARTICLES; CHEMISTRY; POLYMERS AB Nanobiology is a fast-emerging discipline that brings the tools of nanotechnology to the biological sciences. The introduction of new techniques may accelerate the development of highly specific biomedical treatments, increase their efficiency, and minimize their side effects. Introducing foreign bodies into the complex machinery of the human body is, however, a great and humbling challenge, as past experience has shown. In order for nanobiology to reach its full potential, we must devise a means to alter the properties of nanoparticles, as expressed in the human body, in a predictable manner. Computer-aided methods are the natural option to speed up the development of these technologies. Yet, the procedures for annotation and simulation of nanoparticle properties must be developed and their limitations understood before computational methods can be fully exploited. In this review we will compare the state of development of nanoscale simulations in the biological sciences to that of the computer-aided drug design efforts in the past, tracing a historical parallel between both disciplines. From this comparison, lessons can be learned and bottlenecks identified, helping to speed up the development of computer-aided nanobiodevice design tools. C1 [Cachau, Raul E.] SAIC Frederick Inc, Natl Canc Inst, ABCC, Frederick, MD USA. [Gonzalez-Nilo, Fernando D.] Univ Talca, CBSM, Talca, Chile. [Ventura, Oscar N.] Univ Republica, Fac Quim, CCPG DETEMA, Montevideo, Uruguay. [Fritts, Martin J.] SAIC Frederick Inc, Natl Canc Inst, Nanotechnol Characterizat Lab, Frederick, MD USA. RP Cachau, RE (reprint author), SAIC Frederick, 430 Miller Dr Frederick, Frederick, MD 21702 USA. EM cachau@ncifcrf.gov RI Gonzalez-Nilo, Fernando/M-5671-2016 OI Gonzalez-Nilo, Fernando/0000-0001-6857-3575 FU NCI NIH HHS [N01-CO-12400] NR 32 TC 4 Z9 5 U1 0 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2007 VL 7 IS 15 BP 1537 EP 1540 DI 10.2174/156802607782194680 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 240IX UT WOS:000251582400014 PM 17897041 ER PT J AU Schou, M Pike, VW Halldin, C AF Schou, Magnus Pike, Victor W. Halldin, Christer TI Development of radioligands for imaging of brain norepinephrine transporters In Vivo with positron emission tomography SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE NET; radioligand; PET; carbon-11; fluorine-18 ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; H-3 DESMETHYLIMIPRAMINE BINDING; HUMAN DOPAMINE TRANSPORTER; NONHUMAN PRIMATE BRAIN; PROOF-OF-CONCEPT; RAT-BRAIN; UPTAKE SITES; SEROTONIN TRANSPORTER; REBOXETINE ANALOGS; UPTAKE INHIBITOR AB In the central nervous system (CNS) and in the periphery, specific proteins (transporters) are responsible for the regulation of the synaptic concentrations of the major monoamine neurotransmitters, noradrenaline (NE), serotonin (5-HT) and dopamine (DA). Several reports have shown that the expression of these transporters within the CNS may be altered in patients with certain neurodegenerative or neuropsychiatric disorders. Therefore, in the CNS the monoamine transporters are major targets for existing and developmental drugs. The best known drugs targeting these transporters are the selective 5-HT reuptake inhibitors (SSRIs) (e.g. citalopram, Celexa (R)) that are most frequently used in the treatment of clinical depression. Selective NE reuptake inhibitors (NRIs) have also found Use for the treatment of depression and other conditions such as attention deficit hyperactivity (ADHD) disorder, Given that the NE transporter (NET) is also a binding site For cocaine and drugs of abuse, there is a great need for a probe to assess the densities of NET in vivo by brain imaging with either positron emission tomography (PET) or single photon emission tomography (SPET), PET in particular has the potential to measure NET densities quantitatively and with high resolution in the human brain in vivo. quality of a PET image depends crucially on the radioligand used in the emission measurement. Commonly used radionuclides ill PET radioligands are carbon-11 (t(1/2) = 20.4 min) and fluorine-18 (t(1/2) = 109.8 min). This review specifically summarizes the present status of the development of C-11- or F-18-labeled ligands as tools for imaging NET in brain with PET in support of neuropsychiatric clinical research and drug development. C1 [Schou, Magnus; Halldin, Christer] Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. [Pike, Victor W.] NIH, NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Schou, M (reprint author), Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. EM magnus.schou@astrazeneca.com FU Intramural NIH HHS NR 98 TC 5 Z9 6 U1 0 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2007 VL 7 IS 18 BP 1806 EP 1816 DI 10.2174/156802607782507411 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 240JA UT WOS:000251582700006 PM 17979789 ER PT J AU Goldammer, T Weikard, R Miziara, MN Brunner, RM Agarwala, R Schaeffer, AA Womack, E Amaral, MEJ AF Goldammer, T. Weikard, R. Miziara, M. N. Brunner, R. M. Agarwala, R. Schaeffer, A. A. Womack, E. Amaral, M. E. J. TI A radiation hybrid map of river buffalo (Bubalus bubalis) chromosome 7 and comparative mapping to the cattle and human genomes SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID QUANTITATIVE TRAIT LOCI; HIGH-RESOLUTION; BOVINE CHROMOSOME-6; I LOCI; GENE; FISH; CONSTRUCTION; KARYOTYPE; REGION; 2N=50 AB A preliminary radiation hybrid (RH) map containing 50 loci on chromosome 7 of the domestic river buffalo Bubalus bubalis (BBU; 2n = 50) was constructed based on a comparative mapping approach. The RH map of BBU7 includes thirty-seven gene markers and thirteen microsatellites. All loci have been previously assigned to Bos taurus (BTA) chromosome BTA6, which is known for its association with several economically important milk production traits in cattle. The map consists of two linkage groups spanning a total length of 627.9 cR(5,000). Comparative analysis of the BBU7 RH 5,000 map with BTA6 in cattle gave new evidence for strong similarity between the two chromosomes over their entire length and exposed minor differences in locus order. Comparison of the BBU7 RH 5,000 map with the Homo sapiens (HSA) genome revealed similarity with a large chromosome segment of HSA4. Comparative analysis of loci in both species revealed more variability than previously known in gene order and several chromosome rearrangements including centromere relocation. The data obtained in our study define the evolutionarily conserved segment on BBU7 and HSA4 to be between 3.5 megabases (Mb) and 115.8 Mb in the HSA4 (genome build 36) DNA sequence. Copyright (c) 2008 S. Karger AG, Basel. C1 [Goldammer, T.; Weikard, R.; Brunner, R. M.] Forsch Inst Biol Landwirtschaftlicher Nutztiere, Forschungsereich Mol Biol, D-18196 Dummerstorf, Germany. [Miziara, M. N.; Amaral, M. E. J.] UNESP, IBILCE, Inst Biociencias, Dept Biol, Sao Jose Do Rio Preto, SP, Brazil. [Agarwala, R.; Schaeffer, A. A.] Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Services, Bethesda, MD USA. [Womack, E.; Amaral, M. E. J.] Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX USA. RP Goldammer, T (reprint author), Forsch Inst Biol Landwirtschaftlicher Nutztiere, Forschungsereich Mol Biol, Wilhelm Stahl Allee 2, D-18196 Dummerstorf, Germany. EM tomgoldammer@fbn-dummerstorf.de RI Amaral, Elisabete/K-9246-2013; OI Goldammer, Tom/0000-0003-1215-5504 FU Intramural NIH HHS [Z01 LM000097-07] NR 37 TC 8 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2007 VL 119 IS 3-4 BP 235 EP 241 DI 10.1159/000112067 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 262SA UT WOS:000253167100010 PM 18253035 ER PT J AU Griffin, CA Morsberger, L Hawkins, AL Haddadin, M Patel, A Ried, T Schrock, E Perlman, EJ Jaffee, E AF Griffin, C. A. Morsberger, L. Hawkins, A. L. Haddadin, M. Patel, A. Ried, T. Schrock, E. Perlman, E. J. Jaffee, E. TI Molecular cytogenetic characterization of pancreas cancer cell lines reveals high complexity chromosomal alterations SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; HOMOZYGOUS DELETIONS; FREQUENT GAIN; COPY NUMBER; ADENOCARCINOMA; AMPLIFICATION; ABNORMALITIES; CARCINOMA; REARRANGEMENTS; ABERRATIONS AB Karyotype analysis can provide clues to significant genes involved in the genesis and growth of pancreas cancer. The genome of pancreas cancer is complex, and G-band analysis cannot resolve many of the karyotypic abnormalities seen. We studied the karyotypes of 15 recently established cell lines using molecular cytogenetic tools. Comparative genomic hybridization (CGH) analysis of all 15 lines identified genomic gains of 3q, 8q, 11q, 17q, and chromosome 20 in nine or more cell lines. CGH confirmed frequent loss of chromosome 18, 17p, 6q, and 8p. 14/15 cell lines demonstrated loss of chromosome 18q, either by loss of a copy of chromosome 18 (n = 5), all of 18q (n = 7) or portions of 18q (n = 2). Multicolor FISH (Spectral Karyotyping, or SKY) of 11 lines identified many complex structural chromosomal aberrations. 93 structurally abnormal chromosomes were evaluated, for which SKY added new information to 67. Several potentially site-specific recurrent rearrangements were observed. Chromosome region 18q11.2 was recurrently involved in nine cell lines, including formation of derivative chromosomes 18 from a t(18; 22) (three cell lines), t(17; 18) (two cell lines), and t(12; 18), t(15; 18), t(18; 20), and ins(6; 18) (one cell line each). To further define the breakpoints involved on chromosome 18, YACs from the 18q11.2 region, spanning approximately 8 Mb, were used to perform targeted FISH analyses of these lines. We found significant heterogeneity in the breakpoints despite their G-band similarity, including multiple independent regions of loss proximal to the already identified loss of DPC4 at 18q21. Copyright (C) 2007 S. Karger AG, Basel. C1 [Griffin, C. A.; Morsberger, L.; Hawkins, A. L.; Haddadin, M.; Patel, A.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Jaffee, E.] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA. [Ried, T.; Schrock, E.] NHGRI, Bethesda, MD USA. RP Griffin, CA (reprint author), Johns Hopkins Univ Hosp, Dept Pathol, Pk SB202,600 N Wolfe St, Baltimore, MD 21287 USA. EM cgriffin@jhmi.edu FU NCI NIH HHS [P50CA62924] NR 36 TC 17 Z9 19 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2007 VL 118 IS 2-4 BP 148 EP 156 DI 10.1159/000108295 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 239XJ UT WOS:000251551300007 PM 18000365 ER PT J AU Phelan, MC Mitz, AR AF Phelan, Mary C. Mitz, Andrew R. TI Phelan-McDermid syndrome in several family members due to malsegregation of a t(19;22) SO CYTOGENETIC AND GENOME RESEARCH LA English DT Meeting Abstract CT 39th Biennial American Cytogenetics Conference CY APR 27-30, 2006 CL Lake Lanier, GA C1 TC Thomson Childrens Hosp, Chattanooga, TN USA. NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2007 VL 116 IS 4 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 159SA UT WOS:000245885400047 ER PT J AU Davis, BH Holden, JT Bene, MC Borowitz, MJ Braylan, RC Cornfield, D Gorczyca, W Lee, R Maiese, R Orfao, A Wells, D Wood, BL Stetler-Stevenson, M AF Davis, B. H. Holden, J. T. Bene, M. C. Borowitz, M. J. Braylan, R. C. Cornfield, D. Gorczyca, W. Lee, R. Maiese, R. Orfao, A. Wells, D. Wood, B. L. Stetler-Stevenson, M. TI 2006 Bethesda international consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia: Medical indications SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review DE leukemia diagnosis; lymphoma diagnosis; myelodysplasia; multiple myeloma; lymphoproliferative disorder ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; FINE-NEEDLE-ASPIRATION; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; PEDIATRIC-ONCOLOGY-GROUP; NON-HODGKIN-LYMPHOMA AB The clinical indications for diagnostic flow cytometry studies are an evolving consensus, as the knowledge of antigenic definition of hematolymphoid malignancies and the prognostic significance of antigen expression evolves. Additionally the standard of care is not routinely communicated to practicing clinicians and diagnostic services, especially as may relate to new technologies. Accordingly there is often uncertainty on the part of clinicians, payers of medical services, diagnostic physicians and scientists as to the appropriate use of diagnostic flow cytometry. In an attempt to communicate contemporary diagnostic utility of immunophenotypic flow cytometry in the diagnosis and follow-up of patients with hematolymphoid malignancies, the Clinical Cytometry Society organized a two day meeting of international experts in this area to reach a consensus as to this diagnostic tool. This report summarizes the appropriate use of diagnostic flow cytometry as determined by unanimous approval of these experienced practitioners. (c) 2007 Clinical Cytometry Society C1 Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA USA. Univ Nancy 1, Fac Med, Lab Immunol CHU, Nancy, France. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD USA. Univ Florida, Dept Pathol, Gainesville, FL USA. Lehigh Valley Hosp Ctr, Dept Pathol, Allentown, PA USA. Genzyme, New York, NY USA. Mol Pathol Lab Network, Shelton, CT USA. Ameripath, Shelton, CT USA. Univ Salamanca, Univ Hosp, Ctr Invest Canc, Serv Cytometry, Salamanca, Spain. Hematologics, Seattle, WA USA. Univ Washington, Dept Lab Med, Seattle, WA USA. NIH, NCI, Pathol Lab, Bethesda, MD USA. RP Davis, BH (reprint author), PO Box 67, Brewer, ME USA. EM brucedavis@trilliumdx.com RI 2007, Secribsal/A-1556-2012 NR 187 TC 37 Z9 39 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2007 VL 72B SU 1 BP S5 EP S13 DI 10.1002/cyto.b.20365 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 207VN UT WOS:000249279300004 PM 17803188 ER PT J AU Mccoy, JP AF Mccoy, J. Philip, Jr. TI Bethesda International Consensus Conference on flow cytometric immunophenotyping of hematolymphoid neoplasia - July 2006 - Introduction SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material C1 NIH, NHLBI, Bethesda, MD 20892 USA. RP Mccoy, JP (reprint author), NIH, NHLBI, Flow Cytometry Core, Bldg 10, Rm 4A07, 10 Ctr Dr, Bethesda, MD 20892 USA. EM mccoyjp@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2007 VL 72B SU 1 BP S1 EP S1 DI 10.1002/cyto.b.20361 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 207VN UT WOS:000249279300001 ER PT J AU Stetler-Stevenson, M Davis, B Wood, B Braylan, R AF Stetler-Stevenson, Maryalice Davis, Bruce Wood, Brent Braylan, Raul TI 2006 Bethesda International Consensus Conference on flow cytometric immunophenotyping of hematolymphoid neoplasia - Perspective SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material C1 NIH, NCI, Pathol Lab, Bethesda, MD 20892 USA. Trillium Diagnost, Brewer, ME USA. Univ Washington, Seattle, WA 98195 USA. Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. RP Stetler-Stevenson, M (reprint author), NIH, NCI, Pathol Lab, Bldg 10, Rm 2A-33, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov NR 0 TC 6 Z9 7 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2007 VL 72B SU 1 BP S3 EP S3 DI 10.1002/cyto.b.20362 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 207VN UT WOS:000249279300003 PM 17630651 ER PT J AU Wilson, WH AF Wilson, Wyndham H. TI International consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material C1 Natl Inst Hlth, Natl Canc Inst, Canc Res Ctr, Bethesda, MD USA. RP Wilson, WH (reprint author), NCI, Canc Res Ctr, Metab Branch, Bldg 10, Rm 4-N-115, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 0 TC 3 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2007 VL 72B SU 1 BP S2 EP S2 DI 10.1002/cyto.b.20366 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 207VN UT WOS:000249279300002 PM 17803186 ER PT J AU St Croix, B AF St Croix, B. TI Vaccines targeting tumor vasculature: a new approach for cancer immunotherapy SO CYTOTHERAPY LA English DT Editorial Material ID DNA VACCINE; ENDOTHELIAL MARKER-8; COLORECTAL-CANCER; GROWTH; ANGIOGENESIS; CELLS; IMMUNIZATION; BEVACIZUMAB; RECEPTOR-2; THERAPY C1 NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP St Croix, B (reprint author), NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, Frederick, MD 21702 USA. EM stcroix@ncifcrf.gov NR 23 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1465-3249 EI 1477-2566 J9 CYTOTHERAPY JI Cytotherapy PY 2007 VL 9 IS 1 BP 1 EP 3 DI 10.1080/14653240601118444 PG 3 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 140TH UT WOS:000244529100001 ER PT J AU Barrett, AJ AF Barrett, A. J. TI Manipulating regulatory T cells SO CYTOTHERAPY LA English DT Editorial Material C1 NHLBI, Hematol Branch, Stem Cell Allotransplantat Sect, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, Stem Cell Allotransplantat Sect, NIH, 10,CRC Room 3E-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM barrettjj@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2007 VL 9 IS 2 BP 109 EP 110 DI 10.1080/14653240701217476 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 164BX UT WOS:000246208700001 PM 17453962 ER PT J AU Rezvani, K Price, DA Brenchley, JM Kilical, Y Gostick, E Sconocchia, G Hansmann, K Kurlander, R Douek, DC Barrett, AJ AF Rezvani, K. Price, D. A. Brenchley, J. M. Kilical, Y. Gostick, E. Sconocchia, G. Hansmann, K. Kurlander, R. Douek, D. C. Barrett, A. J. TI Transfer of PR1-specific T-cell clones from donor to recipient by stem cell transplantation and association with GvL activity SO CYTOTHERAPY LA English DT Article DE PR1; GVL; CML ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; LYMPHOCYTES; TRANSFUSIONS; EXPANSIONS; EXPRESSION; RESPONSES; DISEASE; BLOOD AB Background The curative effects of GvL following transfer of donor-derived T cells during allogeneic stem cell transplantation (SCT) are well established. However, little is known about the nature, origin and kinetics of the anti-leukemic T-cell responses involved. Methods We used quantitative real-time PCR (qRT-PCR) for interferon-gamma mRNA production (IFN-gamma) and PR1/HLA-A*0201 tetramer staining to detect PR1-specific CD8+ T-cell activity in a donor and a patient with CML. Unbiased strand switch anchored RT-PCR was used to further characterize specific clones in PR1 sorted CD8+ T-cell populations. Results We identified PR1-specific CD8+ T-cell clones from a donor pre-transplant, and demonstrated their transfer in the recipient's blood post-SCT using molecular tracking of Ag-specific T-cell receptors. PR1-specific CD8+ T-cell populations were polyclonal, with a range of functional avidities for cognate Ag, and displayed predominantly effector memory phenotype early post-SCT, suggesting active stimulation in vivo. Expansion of these PR1-specific CD8+ T-cell clones in the recipient was followed by complete remission of CML. Discussion This report represents the first direct demonstration that PR1-specific CD8+ T-cell clones can be transferred during SCT, and supports the feasibility of pre-transplant vaccination strategies that aim to boost the number of anti-leukemic T cells in the graft. C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Oxford, Nuffield Dept Clin Med, Oxford, England. Ctr Clin, Dept Lab Med, NIH, Bethesda, MD USA. RP Rezvani, K (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Rezvanik@nhlbi.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G0501963] NR 19 TC 29 Z9 29 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2007 VL 9 IS 3 BP 245 EP 251 DI 10.1080/14653240701218524 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 166FN UT WOS:000246363700007 PM 17464756 ER PT J AU Cannon, RO Dunbar, CE AF Cannon, R. O., III Dunbar, C. E. TI BM-derived cell therapies for cardiovascular disease SO CYTOTHERAPY LA English DT Review ID ENDOTHELIAL PROGENITOR CELLS; MESENCHYMAL STEM-CELLS; COLONY-STIMULATING FACTOR; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; BONE-MARROW-CELLS; RANDOMIZED CONTROLLED-TRIAL; IMPROVES CARDIAC-FUNCTION; E-KNOCKOUT MICE; MONONUCLEAR-CELLS C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10-CRC,Room 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM cannonr@nhlbi.nih.gov NR 88 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2007 VL 9 IS 4 BP 305 EP 315 DI 10.1080/14653240701431176 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 196TL UT WOS:000248505000001 PM 17573606 ER PT J AU Barrett, J AF Barrett, J. TI Are UC blood transplants prone to developing leukemia? SO CYTOTHERAPY LA English DT Editorial Material ID CELLS C1 NHLBI, Natl Inst Hlth, Hermatol Branch, Bethesda, MD USA. RP Barrett, J (reprint author), NIH, CRC, Rm 3-5330,10 Ctr Dr, Bethesda, MD USA. EM barrettj@nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2007 VL 9 IS 7 BP 611 EP 612 DI 10.1080/14653240701650346 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 233JM UT WOS:000251087200001 PM 17917878 ER PT J AU Hall, MD Failes, TW Yamamoto, N Hambley, TW AF Hall, Matthew D. Failes, Timothy W. Yamamoto, Natsuho Hambley, Trevor W. TI Bioreductive activation and drug chaperoning in cobalt pharmaceuticals SO DALTON TRANSACTIONS LA English DT Article ID HYPOXIA-SELECTIVE CYTOTOXINS; NITROARYLMETHYL QUATERNARY-SALTS; TIRAPAZAMINE PLUS CISPLATIN; EXPLOITING TUMOR HYPOXIA; SCHIFF-BASE COMPLEXES; ANTITUMOR-ACTIVITY; CO(III) COMPLEXES; FLUORESCENT-PROBE; ALKYNE COMPLEXES; OXIDATION-STATE AB The potential for cobalt(III) complexes in medicine, as chaperones of bioactive ligands, and to target tumours through bioreductive activation, has been examined over the past 20 years. Despite this, chemical properties such as reduction potential and carrier ligands required for optimal tumour targeting and drug delivery have not been optimised. Here we review the chemistry of cobalt( III) drug design, and recent developments in the understanding of the cellular fate of these drugs. C1 Univ Sydney, Sch Chem, Ctr Heavy Met Res, Sydney, NSW 2006, Australia. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hambley, TW (reprint author), Univ Sydney, Sch Chem, Ctr Heavy Met Res, Sydney, NSW 2006, Australia. EM t.hambley@chem.usyd.edu.au RI Hall, Matthew/B-2132-2010 NR 75 TC 63 Z9 63 U1 2 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-9226 J9 DALTON T JI Dalton Trans. PY 2007 IS 36 BP 3983 EP 3990 DI 10.1039/b707121c PG 8 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 208UV UT WOS:000249345600001 PM 17828357 ER PT J AU Brechbiel, MW AF Brechbiel, Martin W. TI Targeted alpha-therapy: past, present, future? SO DALTON TRANSACTIONS LA English DT Article ID PARTICLE-MEDIATED RADIOIMMUNOTHERAPY; DISSEMINATED PERITONEAL DISEASE; BIFUNCTIONAL CHELATING-AGENT; ACTIVATOR INHIBITOR TYPE-2; IN-VIVO; MONOCLONAL-ANTIBODY; MAMMALIAN-CELLS; PROSTATE-CANCER; EMITTING RADIONUCLIDE; CARCINOMA XENOGRAFTS AB Monoclonal antibodies have become a viable strategy for the delivery of therapeutic, particle emitting radionuclides specifically to tumor cells to either augment anti-tumor action of the native antibodies or to solely take advantage of their action as targeting vectors. Proper and rational selection of radionuclide and antibody combinations is critical to making radioimmunotherapy ( RIT) a standard therapeutic modality due to the fundamental and significant differences in the emission of either alpha- and beta-particles. The alpha-particle has a short path length ( 50-80 mu m) that is characterized by high linear energy transfer ( 100 keV mu m(-1)). Actively targeted alpha-therapy potentially offers a more specific tumor cell killing action with less collateral damage to the surrounding normal tissues than beta-emitters. These properties make targeted alpha-therapy an appropriate therapy to eliminate minimal residual or micrometastatic disease. RIT using alpha-emitters such as Bi-213, At-211, Ac-225, and others has demonstrated significant activity in both in vitro and in vivo model systems. Limited numbers of clinical trials have progressed to demonstrate safety, feasibility, and therapeutic activity of targeted alpha-therapy, despite having to traverse complex obstacles. Further advances may require more potent isotopes, additional sources and more efficient means of isotope production. Refinements in chelation and/or radiolabeling chemistry combined with rational improvements of isotope delivery, targeting vectors, molecular targets, and identification of appropriate clinical applications remain as active areas of research. Ultimately, randomized trials comparing targeted alpha-therapy combined with integration into existing standards of care treatment regimens will determine the clinical utility of this modality. C1 NCI, NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bldg 10,Room 1B40 10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov FU Intramural NIH HHS [Z01 SC006353-24] NR 92 TC 46 Z9 47 U1 3 U2 14 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-9226 J9 DALTON T JI Dalton Trans. PY 2007 IS 43 BP 4918 EP 4928 DI 10.1039/b704726f PG 11 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 225KA UT WOS:000250515600013 PM 17992276 ER PT S AU Wang, JTL Wen, D Shapiro, BA Herbert, KG Li, J Ghosh, K AF Wang, Jason T. L. Wen, Dongrong Shapiro, Bruce A. Herbert, Katherine G. Li, Jing Ghosh, Kaushik BE CohenBoulakia, S Yannen, V TI Toward an integrated RNA motif database SO DATA INTEGRATION IN THE LIFE SCIENCES, PROCEEDINGS SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 4th International Workshop on Data Integration in the Life Sciences CY JUN 27-29, 2007 CL Univ Penn, Philadelphia, PA SP Univ Penn, Sch Engn & Appl Sci, Penn Genom Inst, Microsoft Res HO Univ Penn ID SECONDARY STRUCTURE; STRUCTURE PREDICTION; SEQUENCE; CLASSIFICATION; ALGORITHM AB In this paper we present the design and implementation of an RNA structural motif database, called RmotifDB. The structural motifs stored in RmotifDB come from three sources: (1) collected manually from biomedical literature; (2) submitted by scientists around the world; and (3) discovered by a wide variety of motif mining methods. We present here a motif mining method in detail. We also describe the interface and search mechanisms provided by RmotifDB as well as techniques used to integrate RmotifDB with the Gene Ontology. The RmotifDB system is fully operational and accessible on the Internet at http://datalab.njit.edu/bioinfo/. C1 [Wang, Jason T. L.; Wen, Dongrong] New Jersey Inst Technol, Bioinformat Program, Newark, NJ 07102 USA. [Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Herbert, Katherine G.] Montclair State Univ, Dept Comp Sci, Montclair, NJ 07043 USA. [Li, Jing; Ghosh, Kaushik] New Jersey Inst Technol, Dept Mat Sci, Appl Statistics Program, Newark, NJ 07102 USA. RP Wang, JTL (reprint author), New Jersey Inst Technol, Bioinformat Program, Newark, NJ 07102 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-73254-9 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2007 VL 4544 BP 27 EP + PG 3 WC Biochemical Research Methods; Computer Science, Information Systems SC Biochemistry & Molecular Biology; Computer Science GA BGS72 UT WOS:000250355600004 ER PT J AU de Simone, V Kaplan, L Patronas, N Wassermann, EM Grafman, J AF de Simone, V. Kaplan, L. Patronas, N. Wassermann, E. M. Grafman, J. TI Driving abilities in frontotemporal dementia patients SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE dementia; dementia, frontotemporal; driving; frontal lobe ID HUMAN PREFRONTAL CORTEX; TEMPORAL-LOBE ATROPHY; ALZHEIMERS-DISEASE; SEMANTIC DEMENTIA; OLDER DRIVERS; DIAGNOSTIC-CRITERIA; DECISION-MAKING; FRONTAL VARIANT; CONSENSUS; FEATURES AB Objective: To evaluate driving competency and the relationship between neuropsychiatric symptoms and driving behavior in frontotemporal dementia (FTD) patients. Methods: Fifteen patients with a diagnosis of FTD and 15 healthy controls were administered a driving simulation task. Measures of driving performance and neuropsychiatric symptoms were assessed. Results: The FTD patients received more speeding tickets, ran more stop signs and were involved in more off-road crashes and collisions than the controls. The patients' overall average speed was significantly higher. Driving performance was correlated with agitated behavior. Conclusions: Behavioral changes characteristic of FTD patients have an impact on their driving skills leading to inappropriate driving behavior. Copyright (C) 2007 S. Karger AG, Basel. C1 Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 61 TC 24 Z9 24 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2007 VL 23 IS 1 BP 1 EP 7 DI 10.1159/000096317 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 107JT UT WOS:000242167700001 PM 17047327 ER PT J AU Vasa, RA Roberson-Nay, R Klein, RG Mannuzza, S Moulton, JL Guardino, M Merikangas, A Carlino, AR Pine, DS AF Vasa, Roma A. Roberson-Nay, Roxann Klein, Rachel G. Mannuzza, Salvatore Moulton, John L., III Guardino, Mary Merikangas, Alison Carlino, Anthony R. Pine, Daniel S. TI Memory deficits in children with and at risk for anxiety disorders SO DEPRESSION AND ANXIETY LA English DT Article DE memory; anxiety; children; familial risk; processing efficiency; medial temporal lobe ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; PANIC DISORDER; MAJOR DEPRESSION; SOCIAL PHOBIA; HIPPOCAMPAL VOLUME; CARBON-DIOXIDE; ADOLESCENTS; PARENTS; ASSOCIATIONS AB There are limited data on the neurocognitive correlates of childhood anxiety disorders. The objective of this study was to examine whether visual and verbal memory deficits of nonemotional stimuli are (1) a shared feature of three common childhood anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) or whether these deficits are restricted to specific anxiety disorders, and (2) present in offspring who possess at least one of the following established risk factors for anxiety disorders, parental history of panic disorder (PD), or major depressive disorder (MDD). One hundred and sixty offspring, ages 9-20 years, were recruited from parents with lifetime diagnoses of PD, MDD, PD plus MDD, or neither illness. Different clinicians blindly administered semistructured diagnostic interviews to offspring and parents. Verbal and visual memory subtests of the Wide Range Assessment of Memory and Learning were administered to offspring. The results showed that offspring with ongoing social phobia demonstrated reduced visual but not verbal memory scores compared to those without social phobia when controlling for offspring IQ, separation anxiety disorder, and generalized anxiety disorder. No other offspring anxiety disorder predicted memory performance. Neither parental PD nor parental MDD was associated with offspring memory performance. These findings are relevant to understanding the phenomenology of childhood anxiety disorders and may provide insights into the neural circuits underlying these disorders. C1 Johns Hopkins Univ, Sch Med, Kennedy Krieger Res Inst, Baltimore, MD 21211 USA. NIMH, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. Freedom From Fear, Staten Isl, NY USA. RP Vasa, RA (reprint author), Johns Hopkins Univ, Sch Med, Kennedy Krieger Res Inst, 3901 Greenspring Ave, Baltimore, MD 21211 USA. EM vasa@kennedykrieger.org NR 51 TC 19 Z9 23 U1 2 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2007 VL 24 IS 2 BP 85 EP 94 DI 10.1002/da.20193 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 149LE UT WOS:000245147600002 PM 16850413 ER PT J AU Kalueff, AV Nutt, DJ AF Kalueff, Allan V. Nutt, David J. TI Role of GABA in anxiety and depression SO DEPRESSION AND ANXIETY LA English DT Review DE GABA; anxiety; depression; benzodiazepine receptors; common pathogenesis ID POSTTRAUMATIC-STRESS-DISORDER; FORCED SWIMMING TEST; DIAZEPAM-BINDING INHIBITOR; ELEVATED PLUS-MAZE; OLFACTORY-BULBECTOMIZED RAT; BIPOLAR AFFECTIVE-DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; BENZODIAZEPINE-RECEPTOR-BINDING; INDUCED BEHAVIORAL DEPRESSION; POSITRON EMISSION TOMOGRAPHY AB This review assesses the parallel data on the role of gamma-aminobutyric acid (GABA) in depression and anxiety. We review historical and new data from both animal and human experimentation which have helped define the key role for this transmitter in both these mental pathologies. By exploring the overlap in these conditions in terms of GABAergic neurochemistry, neurogenetics, brain circuitry, and pharmacology, we develop a theory that the two conditions are intrinsically interrelated. The role of GABAergic agents in demonstrating this interrelationship and in pointing the way to future research is discussed. C1 Univ Bristol, Sch Med Sci, Psychopharmacol Unit, Bristol BS8 1TD, Avon, England. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Nutt, DJ (reprint author), Univ Bristol, Sch Med Sci, Psychopharmacol Unit, Bristol BS8 1TD, Avon, England. EM David.J.Nutt@bristol.ac.uk OI nutt, david/0000-0002-1286-1401 FU Intramural NIH HHS NR 345 TC 154 Z9 166 U1 6 U2 43 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2007 VL 24 IS 7 BP 495 EP 517 DI 10.1002/da.20262 PG 23 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 227MQ UT WOS:000250661200008 PM 17117412 ER PT J AU Radoja, N Guerrini, L Lo Iacono, N Merlo, GR Costanzo, A Weinberg, WC La Mantia, G Calabro, V Morasso, MI AF Radoja, Nadezda Guerrini, Luisa Lo Iacono, Nadia Merlo, Giorgio R. Costanzo, Antonio Weinberg, Wendy C. La Mantia, Girolama Calabro, Viola Morasso, Maria I. TI Homeobox gene Dlx3 is regulated by p63 during ectoderm development: relevance in the pathogenesis of ectodermal dysplasias SO DEVELOPMENT LA English DT Article DE Dlx3; p63; transcription; ectodermal dysplasias; mouse development ID P53 HOMOLOG; MICE LACKING; DIFFERENTIATION; LIMB; IDENTIFICATION; KERATINOCYTES; ORGANOGENESIS; MORPHOGENESIS; EXPRESSION; ISOFORMS AB Ectodermal dysplasias (EDs) are a group of human pathological conditions characterized by anomalies in organs derived from epithelial-mesenchymal interactions during development. Dlx3 and p63 act as part of the transcriptional regulatory pathways relevant in ectoderm derivatives, and autosomal mutations in either of these genes are associated with human EDs. However, the functional relationship between both proteins is unknown. Here, we demonstrate that Dlx3 is a downstream target of p63. Moreover, we show that transcription of Dlx3 is abrogated by mutations in the sterile alpha-motif (SAM) domain of p63 that are associated with ankyloblepharon-ectodermal dysplasia-clefting (AEC) dysplasias, but not by mutations found in ectrodactylyectodermal dysplasia-cleft lip/palate ( EEC), Limb-mammary syndrome (LMS) and split hand-foot malformation (SHFM) dysplasias. Our results unravel aspects of the transcriptional cascade of events that contribute to ectoderm development and pathogenesis associated with p63 mutations. C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. Univ Milan, Dept Biomol & Biotechnol Sci, I-20133 Milan, Italy. CNR, Inst Tecnol Biomed, Dulbecci Telethon Inst, I-20100 Milan, Italy. Univ Roma Tor Vergata, Dept Dermatol, I-00133 Rome, Italy. FDA, Div Monoclonal Antibodies, CDER, Bethesda, MD 20892 USA. Univ Naples, Dept Struct & Funct Biol, I-80126 Naples, Italy. RP Morasso, MI (reprint author), NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. EM morassom@mail.nih.gov RI Weinberg, Wendy/A-8920-2009; Costanzo, Antonio/D-3896-2012; OI Costanzo, Antonio/0000-0001-9697-2557 FU Intramural NIH HHS; Telethon [GGP030326] NR 32 TC 35 Z9 36 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN 1 PY 2007 VL 134 IS 1 BP 13 EP 18 DI 10.1242/dev.02703 PG 6 WC Developmental Biology SC Developmental Biology GA 119KK UT WOS:000243011000003 PM 17164413 ER PT J AU Zhang, YZ Rath, N Hannenhalli, S Wang, ZS Cappola, T Kimura, S Atochina-Vasserman, E Lu, MM Beers, MF Morrisey, EE AF Zhang, Yuzhen Rath, Nibedita Hannenhalli, Sridhar Wang, Zhishan Cappola, Thomas Kimura, Shioko Atochina-Vasserman, Elena Lu, Min Min Beers, Michael F. Morrisey, Edward E. TI GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo SO DEVELOPMENT LA English DT Article DE GATA; Nkx; transcription factor; synergy; lung; mouse ID STEAROYL-COA DESATURASE; LUNG EPITHELIAL-CELLS; SERUM RESPONSE FACTOR; SURFACTANT PROTEIN-B; TRANSCRIPTION FACTOR; C/EBP-ALPHA; RBP-L; DIFFERENTIATION; MORPHOGENESIS; ENHANCER AB In vitro studies have suggested that members of the GATA and Nkx transcription factor families physically interact, and synergistically activate pulmonary epithelial- and cardiac-gene promoters. However, the relevance of this synergy has not been demonstrated in vivo. We show that Gata6-Titf1 (Gata6-Nkx2.1) double heterozygous (G6-Nkx DH) embryos and mice have severe defects in pulmonary epithelial differentiation and distal airway development, as well as reduced phospholipid production. The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary dysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf1 ( Nkx2.1). These studies indicate that Gata6 and Nkx2.1 act in a synergistic manner to direct pulmonary epithelial differentiation and development in vivo, providing direct evidence that interactions between these two transcription factor families are crucial for the development of the tissues in which they are co-expressed. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. RP Morrisey, EE (reprint author), Univ Penn, Dept Med, Philadelphia, PA 19104 USA. EM emorrise@mail.med.upenn.edu FU NHLBI NIH HHS [HL064520, HL064632, HL074064, R01 HL088577] NR 47 TC 48 Z9 50 U1 1 U2 3 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 JAN 1 PY 2007 VL 134 IS 1 BP 189 EP 198 DI 10.1242/dev.02720 PG 10 WC Developmental Biology SC Developmental Biology GA 119KK UT WOS:000243011000020 PM 17164424 ER PT J AU Song, LY Fassler, R Mishina, Y Jiao, K Baldwin, HS AF Song, Lanying Faessler, Reinhard Mishina, Yuji Jiao, Kai Baldwin, H. Scott TI Essential functions of Alk3 during AV cushion morphogenesis in mouse embryonic hearts SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Alk3; atrioventricular cushion; BMP; cardiogenesis; congenital heart diseases; epithelial-mesenchymal transformation (EMT) ID ENDOCARDIAL CUSHION; TRANSCRIPTION FACTORS; TOOTH DEVELOPMENT; PROTEIN-RECEPTOR; NF-ATC; EXPRESSION; APOPTOSIS; VALVES; CELLS; MICE AB Accumulated evidence has suggested that BMP pathways play critical roles during mammalian cardiogenesis and impairment of BMP signaling may contribute to human congenital heart diseases (CHDs), which are the leading cause of infant morbidity and mortality. Alk3 encodes a BMP specific type I receptor expressed in mouse embryonic hearts. To reveal functions of Alk3 during atrioventricular (AV) cushion morphogenesis and to overcome the early lethality of Alk3(-/-) embryos, we applied a Cre/loxp approach to specifically inactivate Alk3 in the endothelium/endocardium. Our studies showed that endocardial depletion of Alk3 severely impairs epithelium-mesenchymal-transforrnation (EMT) in the atrioventricular canal (AVC) region; the number of mesenchymal cells formed in Tie1-Cre;Alk3(loxp/loxp) embryos was reduced to only similar to 20% of the normal level from both in vivo section studies and in vitro explant assays. We showed, for the first time, that in addition to its functions on mesenchyme formation, Alk3 is also required for the normal growth/survival of AV cushion mesenchymal cells. Functions of Alk3 are accomplished through regulating expression/activation/subcellular localization of multiple downstream genes including Smads and cell-cycle regulators. Taken together, our study supports the notion that Alk3-mediated BMP signaling in AV endocardial/mesenchymal cells plays a central role during cushion morphogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Ctr Med, Dept Pediat, Div Pediat Cardiol, Nashville, TN 37232 USA. Univ Alabama, Dept Genet, Div Genet & Translat Med, Birmingham, AL 35394 USA. Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany. Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Ctr Med, Dept Pediat, Div Pediat Cardiol, Nashville, TN 37232 USA. RP Jiao, K (reprint author), Vanderbilt Univ, Ctr Med, Dept Pediat, Div Pediat Cardiol, 221 Kirkland Hall, Nashville, TN 37232 USA. EM kjiao@uab.edu; scott.baldwin@Vanderbilt.edu FU NHLBI NIH HHS [5 P50 HL56401-09] NR 52 TC 58 Z9 58 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2007 VL 301 IS 1 BP 276 EP 286 DI 10.1016/j.ydbio.2006.08.004 PG 11 WC Developmental Biology SC Developmental Biology GA 125UG UT WOS:000243467800024 PM 16959237 ER PT J AU Beaucher, M Goodliffe, J Hersperger, E Trunova, S Frydman, H Shearn, A AF Beaucher, Michelle Goodliffe, Julie Hersperger, Evelyn Trunova, Svetlana Frydman, Horacio Shearn, Allen TI Drosophila brain tumor metastases express both neuronal and glial cell type markers SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila; metastasis; lethal giant larvae; brain tumor ID NEUROBLAST SELF-RENEWAL; STEM-CELLS; SUPPRESSOR GENES; CANCER; PROTEIN; LGL; POLARITY; GROWTH; APKC; DIFFERENTIATION AB Loss of either lgl or brat gene activity in Drosophila larvae causes neoplastic brain tumors. Fragments of tumorous brains from either mutant transplanted into adult hosts over-proliferate, and kill their hosts within 2 weeks. We developed an in vivo assay for the metastatic potential of tumor cells by quantifying micrometastasis formation within the ovarioles of adult hosts after transplantation and determined that specific metastatic properties of lgl and brat tumor cells are different. We detected micrometastases in 15.8% of ovarioles from wild type host females 12 days after transplanting lgl tumor cells into their abdominal cavities. This frequency increased significantly with increased proliferation time. We detected micrometastases in 15% of ovarioles from wild type host females 10 days after transplanting brat tumor cells into their abdominal cavities. By contrast.. this frequency did not change significantly with increased proliferation time. We found that nearly all lgl micrometastases co-express the neuronal cell marker, ELAV, and the glial cell marker, REPO. These markers are not co-expressed in normal brain cells nor in tumorous brain cells. This indicates deregulated gene expression in these metastatic cells. By contrast, most of the brat micrometastases expressed neither marker. While mutations in both lgl and brat cause neoplastic brain tumors, our results reveal that metastatic cells arising from these tumors have quite different properties. These data may have important implications for the treatment of tumor metastasis. (c) 2006 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Shearn, A (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. EM bio_cals@jhu.edu OI Frydman, Horacio/0000-0003-0191-7948 FU NIGMS NIH HHS [R01 GM060410-03, R01 GM060410-04, R01 GM060410-01A2, R01 GM060410-02] NR 34 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2007 VL 301 IS 1 BP 287 EP 297 DI 10.1016/j.ydbio.2006.09.019 PG 11 WC Developmental Biology SC Developmental Biology GA 125UG UT WOS:000243467800025 PM 17055475 ER PT J AU Willer, CJ Bonnycastle, LL Conneely, KN Duren, WL Jackson, AU Scott, LJ Narisu, N Chines, PS Skol, A Stringham, HM Petrie, J Erdos, MR Swift, AJ Enloe, ST Sprau, AG Smith, E Tong, M Doheny, KF Pugh, EW Watanabe, RM Buchanan, TA Valle, TT Bergman, RN Tuomilehto, J Mohlke, KL Collins, FS Boehnke, M AF Willer, Cristen J. Bonnycastle, Lori L. Conneely, Karen N. Duren, William L. Jackson, Anne U. Scott, Laura J. Narisu, Narisu Chines, Peter S. Skol, Andrew Stringham, Heather M. Petrie, John Erdos, Michael R. Swift, Amy J. Enloe, Sareena T. Sprau, Andrew G. Smith, Eboni Tong, Maurine Doheny, Kimberly F. Pugh, Elizabeth W. Watanabe, Richard M. Buchanan, Thomas A. Valle, Tinto T. Bergman, Richard N. Tuomilehto, Jaakko Mohlke, Karen L. Collins, Francis S. Boehnke, Michael TI Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes SO DIABETES LA English DT Article ID NUCLEAR FACTOR-4-ALPHA GENE; IMPAIRED GLUCOSE-TOLERANCE; GENOME-WIDE ASSOCIATION; PROMOTER POLYMORPHISM; INSULIN-RESISTANCE; COMPLEX TRAITS; COMMON VARIATION; HNF1-ALPHA GENE; KIR6.2 KCNJ11; SUR1 ABCC8 AB More than 120 published reports have described associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. However, multiple studies of the same variant have often been discordant. From a literature search, we identified previously reported type 2 diabetes-associated SNPs. We initially genotyped 134 SNPs on 786 index case subjects from type 2 diabetes families and 617 control subjects with normal glucose tolerance from Finland and excluded from analysis 20 SNPs in strong linkage disequilibrium (r(2) > 0.8) with another typed SNP. Of the 114 SNPs examined, we followed up the 20 most significant SNPs (P < 0.10) on an additional 384 case subjects and 366 control subjects from a population-based study in Finland. In the combined data, we replicated association (P < 0.05) for 12 SNPs: PPARG Pro12Ala and His447, KCNJ11 Glu23Lys and rs5210, TNF -857, SLC2A2 Ile110Thr, HNF1A/TCF1 rs2701175 and GE117881_360, PCK1 -232, NEUROD1 Thr45Ala, IL6 -598, and ENPP1 Lys121Gln. The replication of 12 SNPs of 114 tested was significantly greater than expected by chance under the null hypothesis of no association (P = 0.012). We observed that SNPs from genes that had three or more previous reports of association were significantly more likely to be replicated in our sample (P = 0.03), although we also replicated 4 of 58 SNPs from genes that had only one previous report of association. C1 Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Div Endocrinol, Dept Med, Los Angeles, CA USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. S Ostrobothnia Cent Hosp, Seinajoki, Finland. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. RP Boehnke, M (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, 1420 Washington Hts, Ann Arbor, MI 48109 USA. EM boehnke@umich.edu OI Willer, Cristen/0000-0001-5645-4966 FU Intramural NIH HHS; NHGRI NIH HHS [1Z01HG000024-11]; NIDDK NIH HHS [DK27619, DK29867, DK62370, DK72193, R01 DK029867, R01 DK072193] NR 55 TC 68 Z9 75 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2007 VL 56 IS 1 BP 256 EP 264 DI 10.2337/db06-0461 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 125TY UT WOS:000243466900034 PM 17192490 ER PT J AU Sosenko, JM Palmer, JP Greenbaum, CJ Mahon, J Cowie, C Krischer, JP Chase, HP White, NH Buckingham, B Herold, KC Cuthbertson, D Skyler, JS AF Sosenko, Jay M. Palmer, Jerry P. Greenbaum, Carla J. Mahon, Jeffrey Cowie, Catherine Krischer, Jeffrey P. Chase, H. Peter White, Neil H. Buckingham, Bruce Herold, Kevan C. Cuthbertson, David Skyler, Jay S. CA Diabet Prevention Trial Type 1 Stu TI Increasing the accuracy of oral glucose tolerance testing and extending its application to individuals with normal glucose tolerance for the prediction of type 1 diabetes - The Diabetes Prevention Trial-Type 1 SO DIABETES CARE LA English DT Article ID BETA-CELL FUNCTION; FOLLOW-UP; INSULIN; MELLITUS; RELATIVES; AUTOANTIBODIES; PROGRESSION; TRIAL AB OBJECTIVE - We assessed the extent to which both standard and alternative indexes from 2-h oral glucose tolerance testing predict type 1 diabetes and whether oral glucose tolerance tests (OGTTs) predict type 1 diabetes in individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS - The prediction of type 1 diabetes from baseline OGTTs was studied in 704 Diabetes Prevention Trial-Type 1 participants (islet-cell autoantibody [ICA] -positive relatives of type 1 diabetic patients). The maximum follow-up was 7.4 years. Analyses utilized receiver-operator curves (ROCs), proportional hazards models, and survival curves. RESULTS - ROC areas under the curve (ROCAUCs) for both the AUC glucose (0.73 +/- 0.02) and an CGTT prediction index (0.78 +/- 0.02) were higher (P < 0.001) than those for the fasting (0.53 +/- 0.02) and 2-h glucose (0.66 +/- 0.02). RCCAUCs for the 60- and 90-min glucose (0.71 +/- 0.02 and 0.72 +/- 0.02, respectively) were also higher (P < 0.01) than those for the fasting and 2-h glucose. Among individuals with normal glucose tolerance, OGTTs were highly predictive, with 4th versus 1st quartile hazard ratios for the 2-h glucose, AUC glucose, and OGTT prediction index ranging from 3.77 to 5.30 (P < 0.001 for all). CONCLUSIONS - Certain alternative CGTT indexes appear to better predict type 1 diabetes than standard OGTT indexes in ICA-positive relatives of type 1 diabetic patients. More-over, even among those with normal glucose tolerance, OGTTs are strongly predictive. This suggests that subtle metabolic abnormalities are present several years before the diagnosis of type 1 diabetes. C1 Univ Miami, Div Endocrinol, Miami, FL 33101 USA. Univ Washington, Dept Endocrinol & Metab, Seattle, WA 98195 USA. Virginia Mason, Benaroya Res Inst, Seattle, WA USA. Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 3K7, Canada. NIDDK, NIH, Bethesda, MD USA. Univ S Florida, Div Informat & Biostat, Tampa, FL USA. Barbara Davis Ctr Childhood Diabet, Denver, CO USA. Washington Univ, Dept Pediat Endocrinol & Metab, Sch Med, St Louis, MO USA. Stanford Univ, Dept Pediat Endocrinol, Stanford, CA 94305 USA. Columbia Univ, Div Endocrinol, New York, NY USA. Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, POB 016960 D110, Miami, FL 33101 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016 NR 19 TC 41 Z9 43 U1 1 U2 4 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 JAN PY 2007 VL 30 IS 1 BP 38 EP 42 DI 10.2337/dc06-1615 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 125UZ UT WOS:000243469800007 PM 17192330 ER PT J AU Manosca, F Schinstine, M Fetsch, PA Sorbara, L Wilder, AM Brosky, K Erickson, D Raffeld, M Filie, AC Abati, A AF Manosca, Frances Schinstine, Malcolm Fetsch, Patricia A. Sorbara, Lynn Wilder, Anna Maria Brosky, Keith Erickson, Dana Raffeld, Mark Filie, Armando C. Abati, Andrea TI Diagnostic effects of prolonged storage on fresh effusion samples SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol DE effusion; immunocytochemistry; preservation; storage ID PLEURAL EFFUSIONS; IMMUNOCYTOCHEMISTRY; TIME AB The effects on morphology and diagnostic interpretation of delayed processing of refrigerated effusion samples have not been well documented. The potential for cellular degeneration has led many laboratories to reflexively fix samples rather than submit fresh/refrigerated samples for cytologic examination. We sought to determine if effusion specimens are suitable for morphologic, immunocytochemical, and DNA-based molecular studies after prolonged periods of refrigerated storage time. Ten fresh effusion specimens were refrigerated at 4 degrees C; aliquots were processed at specific points in time (days 0, 3, 5, 7, 10, 14). Specimens evaluated included four pleural (3 benign, I breast adenocarcinoma) and six peritoneal (2 ovarian adenocarcinomas, I malignant melanoma, 2 mesotheliomas, I atypical mesothelial) effusions. The morphology of the cytologic preparations from the 10 effusions was preserved and interpretable after 14 days of storage at 4 degrees C. The immunocytochemical profile of the samples (AE1/AE3, EMA, calretinin, and LCA) was consistent from day 0 to day 14. Amplifiable DNA was present in all samples tested on day 14. We conclude that cytopathologic interpretation of effusion samples remains reliable with refrigeration at 4 degrees C even if processing is delayed. C1 NCI, Pathol Lab, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Pathol Lab, Cytopathol Sect, NIH, 10 Ctr Dr,Bldg 10,Room 2A19, Bethesda, MD 20892 USA. EM abatia@mail.nih.gov NR 5 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JAN PY 2007 VL 35 IS 1 BP 6 EP 11 DI 10.1002/dc.20587 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 123SS UT WOS:000243316600002 PM 17173298 ER PT J AU Pilotto, A Ferrucci, L Scarcelli, C Niro, V Di Mario, F Seripa, D Andriulli, A Leandro, G Franceschi, M AF Pilotto, Alberto Ferrucci, Luigi Scarcelli, Carlo Niro, Valeria Di Mario, Francesco Seripa, Davide Andriulli, Angelo Leandro, Gioacchino Franceschi, Marilisa TI Usefulness of the comprehensive geriatric assessment in older patients with upper gastrointestinal bleeding: A two-year follow-up study SO DIGESTIVE DISEASES LA English DT Article DE comprehensive geriatric assessment; multidimensional prognostic index; upper gastrointestinal bleeding, diagnosis ID ELDERLY PATIENTS; VALIDATION; INDEX; MORTALITY; PROGRESS; USERS AB Background: The potential usefulness of standardized comprehensive geriatric assessment (CGA) in evaluating treatment and follow-up of older patients with upper gastrointestinal bleeding is unknown. Aim: To evaluate the usefulness of the CGA as a 2-year mortality multidimensional prognostic index (MPI) in older patients hospitalized for upper gastrointestinal bleeding. Materials and Methods: Patients aged >= 65 years consecutively hospitalized for acute upper gastrointestinal bleeding were included. Diagnosis of bleeding was based on clinical and endoscopic features. All patients underwent a CGA that included six standardized scales, i. e., Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Short Portable Mental Status Questionnaire (SPMSQ), Mini Nutritional Assessment (MNA), Exton- Smith Score (ESS) and Comorbity Index Rating Scale (CIRS), as well as information on medication history and cohabitation, for a total of 63 items. A MPI was calculated from the integrated total scores and expressed as MPI 1 = low risk, MPI 2 = moderate risk, and MPI 3 = severe risk. The predictive value of the MPI for mortality over a 24-month follow-up was calculated. Results: 36 elderly patients (M 16/F 20, mean age 82.8 +/- 7.9 years, range 70-101 years) were included in the study. A significant difference in mean age was observed between males and females (M 80.1 +/- 4.8 vs. F 84.9 +/- 9.3 years; p < 0.05). The causes of upper gastrointestinal bleeding were duodenal ulcer in 38.8%, gastric ulcer in 22.2%, and erosive gastritis in 16.6% of the patients, while 16.6% had gastrointestinal bleeding from unknown origin. The overall 2-year mortality rate was 30.5%. 18 patients (50%) were classified as having a low- risk MPI (mean value 0.18 +/- 0.09), 12 (33.3%) as having a moderate- risk MPI (mean value 0.48 +/- 0.08) and 6 (16.6%) as having a severe- risk MPI (mean value 0.83 8 0.06). Higher MPI grades were significantly associated with higher mortality ( grade 1 = 12.5%, grade 2 = 41.6%, grade 3 = 83.3%; p = 0.001). Adjusting for age and sex, the prognostic efficacy of MPI for mortality was confirmed and highly significant (odds ratio 10.47, 95% CI 2.04-53.6). Conclusion: CGA is a useful tool for calculating a MPI that significantly predicts the risk of 2- year mortality in older patients with upper gastrointestinal bleeding. Copyright (C) 2007 S. Karger AG, Basel. C1 IRCCS Casa Sollievo Sofferenza, Geriatr Unit, San Giovanni Rotondo, Italy. IRCCS Casa Sollievo Sofferenza, Gerontol & Geriatr Res Labs, San Giovanni Rotondo, Italy. IRCCS Casa Sollievo Sofferenza, Gastroenterol Unit, San Giovanni Rotondo, Italy. Univ Parma, Dept Gastroenterol, I-43100 Parma, Italy. IRCCS Saveiro De Bellis, Gastroenterol Unit, Bari, Italy. NIA, Longitudinal Studies Sect, Harbor Hosp Ctr, Baltimore, MD 21224 USA. RP Pilotto, A (reprint author), Ist Ric & Cura Carattere Sci, Osped Casa Sollievo Sofferenza, Unita Operat Geriatr, IT-71013 San Giovanni Rotondo, Italy. EM alberto.pilotto@libero.it RI Andriulli, Angelo/B-5027-2017; OI Andriulli, Angelo/0000-0001-8862-7083; Leandro, Gioacchino/0000-0001-6624-4532 FU Intramural NIH HHS [Z99 AG999999] NR 20 TC 24 Z9 25 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2007 VL 25 IS 2 BP 124 EP 128 DI 10.1159/000099476 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 165CV UT WOS:000246282400004 PM 17468547 ER PT S AU Spring, KR AF Spring, Kenneth R. BE Sluder, G Wolf, DE TI Cameras for digital microscopy SO DIGITAL MICROSCOPY, 3RD EDITION SE Methods in Cell Biology LA English DT Review; Book Chapter C1 Natl Heart Lund & Blood Inst, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD 20892 USA. RP Spring, KR (reprint author), Natl Heart Lund & Blood Inst, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD 20892 USA. NR 3 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-374025-0 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2007 VL 81 BP 171 EP + DI 10.1016/S0091-679X(06)81010-1 PG 18 WC Cell Biology SC Cell Biology GA BGK14 UT WOS:000247882100010 PM 17519168 ER PT J AU Birrer, M AF Birrer, M. TI Preface SO DISEASE MARKERS LA English DT Editorial Material C1 NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Birrer, M (reprint author), NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2007 VL 23 IS 5-6 BP 353 EP 353 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 249RH UT WOS:000252246900001 ER PT J AU Mok, SC Kwong, J Welch, WR Samimi, G Ozbun, L Bonome, T Birrer, MJ Berkowitz, RS Wong, KK AF Mok, Samuel C. Kwong, Joseph Welch, William R. Samimi, Goli Ozbun, Laurent Bonome, Tomas Birrer, Michael J. Berkowitz, Ross S. Wong, Kwong-Kwok TI Etiology and pathogenesis of epithelial ovarian cancer SO DISEASE MARKERS LA English DT Article DE ovarian cancer; microenvironment; inflammation; pathogenesis ID DELETION UNIT; INCESSANT OVULATION; SURFACE EPITHELIUM; SPONTANEOUS TRANSFORMATION; INFLAMMATORY REACTION; K-RAS; RISK; TUMORS; CELLS; WOMEN AB Ovarian cancer is complex disease composed of different histological grades and types. However, the underlying molecular mechanisms involved in the development of different phenotypes remain largely unknown. Epidemiological studies identified multiple exogenous and endogenous risk factors for ovarian cancer development. Among them, an inflammatory stromal microenvironment seems to play a critical role in the initiation of the disease. The interaction between such a microenvironment, genetic polymorphisms, and different epithelial components such as endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian cortex may induce different genetic changes identified in the epithelial component of different histological types of ovarian tumors. Genetic studies on different histological grades and types provide insight into the pathogenetic pathways for the development of different disease phenotypes. However, the link between all these genetic changes and the etiological factors remains to be established. C1 [Mok, Samuel C.; Kwong, Joseph; Berkowitz, Ross S.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Lab Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Mok, Samuel C.; Berkowitz, Ross S.] Harvard Univ, Dana Farber Canc Ctr, Gillette Ctr Womens Canc, Boston, MA 02115 USA. [Welch, William R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Samimi, Goli; Ozbun, Laurent; Bonome, Tomas; Birrer, Michael J.] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Samimi, Goli] Div Canc Prevent, Off Prevent Oncol, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Wong, Kwong-Kwok] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. RP Mok, SC (reprint author), Brigham & Womens Hosp, Lab Gynecol Oncol, BLI 447,221 Longwood Ave, Boston, MA 02115 USA. EM scmok@rics.bwh.harvard.edu RI Kwong, Joseph/H-2368-2013; OI Wong, Kwong-Kwok/0000-0002-0375-6669 FU NCI NIH HHS [CA105009, R33CA103595] NR 68 TC 23 Z9 25 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2007 VL 23 IS 5-6 BP 367 EP 376 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 249RH UT WOS:000252246900003 PM 18057520 ER PT J AU Samimi, G Ozbun, L Johnson, ME Mok, SC Birrer, MJ AF Samimi, Goli Ozbun, Laurent Johnson, Michael E. Mok, Samuel C. Birrer, Michael J. TI Biomarkers of mucinous tumors of the ovary SO DISEASE MARKERS LA English DT Article ID PROSTATE-CANCER; TISSUE MICROARRAY; GENE-EXPRESSION; CARCINOEMBRYONIC ANTIGEN; PROGNOSTIC-SIGNIFICANCE; CDNA MICROARRAY; BREAST-CANCER; BETA-CATENIN; SERUM MARKER; FIGO STAGE C1 [Samimi, Goli] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Samimi, Goli; Ozbun, Laurent; Birrer, Michael J.] NCI, Ctr Canc Res, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. [Johnson, Michael E.; Mok, Samuel C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Gynecol Oncol, Boston, MA 02115 USA. RP Samimi, G (reprint author), NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. NR 60 TC 4 Z9 4 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2007 VL 23 IS 5-6 BP 389 EP 396 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 249RH UT WOS:000252246900005 PM 18057522 ER PT J AU Kohn, EC Azad, N Annunziata, C Dhamoon, AS Whiteley, G AF Kohn, Elise C. Azad, Nilofer Annunziata, Christina Dhamoon, Amit S. Whiteley, Gordon TI Proteomics as a tool for biomarker discovery SO DISEASE MARKERS LA English DT Article DE ovarian cancer; proteomics; mass spectrometry; biomarker; diagnosis ID SELDI-TOF-MS; OVARIAN-CANCER; BREAST-CANCER; MASS-SPECTROMETRY; SERUM PROTEOMICS; PROSTATE-CANCER; MARKERS; IDENTIFICATION; PATTERNS; DIAGNOSTICS AB Novel technologies are now being advanced for the purpose of identification and validation of new disease biomarkers. A reliable and useful clinical biomarker must a) come from a readily attainable source, such as blood or urine, b) have sufficient sensitivity to correctly identify affected individuals, c) have sufficient specificity to avoid incorrect labeling of unaffected persons, and d) result in a notable benefit for the patient through intervention, such as survival or life quality improvement. Despite these critical descriptors, the few available FDA-approved biomarkers for cancer do not completely fit this definition and their benefits are limited to a small number of cancers. Ovarian cancer exemplifies the need for a diagnostic biomarker of early stage disease. Symptoms are present but not specific to the disease, delaying diagnosis until an advanced and generally incurable stage in over 70% of affected women. As such, diagnostic intervention in the form of oopherectomy can be performed in the appropriate at-risk population if identified such as with a new accurate, sensitive, and specific biomarker. If early stage disease is identified, the requirement for survival and life quality improvement will be met. One of the new technologies applied to biomarker discovery is tour-de-force analysis of serum peptides and proteins. Optimization of mass spectrometry techniques coupled with advanced bioinformatics approaches has yielded informative biomarker signatures discriminating presence of cancer from unaffected in multiple studies from different groups. Validation and randomized outcome studies are needed to determine the true value of these new biomarkers in early diagnosis, and improved survival and quality of life. C1 [Kohn, Elise C.; Azad, Nilofer; Dhamoon, Amit S.; Whiteley, Gordon] NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. [Kohn, Elise C.; Azad, Nilofer; Annunziata, Christina] NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), 10 Ctr Dr MSC1500,Bldg 10,Room B1B51, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov FU Intramural NIH HHS NR 44 TC 29 Z9 30 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2007 VL 23 IS 5-6 BP 411 EP 417 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 249RH UT WOS:000252246900007 PM 18057524 ER PT J AU Farley, J Ozbun, L Samimi, G Birrer, MJ AF Farley, John Ozbun, Laurent Samimi, Goli Birrer, Michael J. TI Cell cycle and related protein SO DISEASE MARKERS LA English DT Article DE gynecologic; malignancies; biologiomarkers ID EPITHELIAL OVARIAN-CANCER; ENDOTHELIAL GROWTH-FACTOR; GYNECOLOGIC-ONCOLOGY-GROUP; PROGRESSION-FREE SURVIVAL; PROGNOSTIC-SIGNIFICANCE; FACTOR EXPRESSION; SUBCELLULAR-LOCALIZATION; P27(KIP1) EXPRESSION; P53 OVEREXPRESSION; FACTOR RECEPTOR C1 [Ozbun, Laurent; Birrer, Michael J.] NCI, Ctr Canc Res, Cell & Canc Biol Dept, Med Branch, Bethesda, MD 20892 USA. [Farley, John] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Samimi, Goli] NCI, Canc Prevent Fellowship Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Samimi, Goli] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Birrer, MJ (reprint author), NCI, Ctr Canc Res, Cell & Canc Biol Dept, Med Branch, 37 Convert Drive,Bldg 37 Room 1130, Bethesda, MD 20892 USA. EM birrerm@bprb.nci.nih.gov NR 57 TC 2 Z9 3 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2007 VL 23 IS 5-6 BP 433 EP 443 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 249RH UT WOS:000252246900009 PM 18057526 ER PT J AU Morin, PJ AF Morin, Patrice J. TI Claudin proteins in ovarian cancer SO DISEASE MARKERS LA English DT Article ID CLOSTRIDIUM-PERFRINGENS ENTEROTOXIN; TIGHT JUNCTION PROTEINS; DIFFERENTIAL GENE-EXPRESSION; MESSENGER-RNA EXPRESSION; SQUAMOUS-CELL CARCINOMA; POTENTIAL MARKERS; PANCREATIC-CANCER; BARRIER FUNCTION; EPITHELIUM; THERAPY AB Members of the claudin family of tight junction proteins have been found altered in several malignancies, including ovarian cancer. Because claudin-3 and -4 are elevated in the vast majority of ovarian tumors, they may represent useful biomarkers for detection and prognosis, as well as ideal targets for therapy using the Clostridium perfringens enterotoxin. C1 NIA, NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Morin, PJ (reprint author), NIA, NIH, Cellular & Mol Biol Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Morinp@grc.nia.nih.gov NR 40 TC 17 Z9 17 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2007 VL 23 IS 5-6 BP 453 EP 457 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 249RH UT WOS:000252246900011 PM 18057528 ER PT B AU Zou, J Le, D Thoma, GR AF Zou, Jie Le, Daniel Thoma, George R. BE King, PR Simske, SJ TI Structure and Content Analysis for HTML Medical Articles: A Hidden Markov Model Approach SO DOCENG'07: PROCEEDINGS OF THE 2007 ACM SYMPOSIUM ON DOCUMENT ENGINEERING LA English DT Proceedings Paper CT 7th ACM Symposium on Document Engineering CY AUG 28-31, 2007 CL Univ Manitoba, Winnipeg, CANADA SP ACM SIGWEB HO Univ Manitoba DE Document Layout Analysis; Document Object Model (DOM); Web Information Retrieval; HTML Document Segmentation; HTML Document Labeling; Text Mining AB We describe ongoing research on segmenting and labeling HTML medical journal articles. In contrast to existing approaches in which HTML tags usually serve as strong indicators, we seek to minimize dependence on HTML tags. Designing logical component models for general Web pages is a challenging task. However, in the narrow domain of online journal articles, we show that the HTML document, modeled with a Hidden Markov Model, can be accurately segmented into logical zones. C1 [Zou, Jie; Le, Daniel; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Zou, J (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM jzou@mail.nih.gov; daniel@mail.nih.gov; gthoma@mail.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 1515 BROADWAY, NEW YORK, NY 10036-9998 USA BN 978-1-59593-776-6 PY 2007 BP 199 EP 201 PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA BKI60 UT WOS:000268220500034 ER PT S AU Kim, IC Le, DX Thoma, GR AF Kim, In Cheol Le, Daniel X. Thoma, George R. BE Lin, X Yanikoglu, BA TI Identification of "comment-on sentences" in online biomedical documents using support vector machines - art. no. 65000O SO Document Recognition and Retrieval XIV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XIV CY JAN 30-FEB 01, 2007 CL San Jose, CA SP Soc Imaging Sci & Technol, SPIE DE "comment-on" identification; online biomedical documents; support vector machine; score function AB MEDLINE (R) is the premier bibliographic online database of the National Library of Medicine, containing approximately 14 million citations and abstracts from over 4,800 biomedical journals. This paper presents an automated method based on support vector machines to identify a "comment-on" list, which is a field in a MEDLINE citation denoting previously published articles commented on by a given article. For comparative study, we also introduce another method based on scoring functions that estimate the significance of each sentence in a given article. Preliminary experiments conducted on HTML-fonnatted online biomedical documents collected from 24 different journal titles show that the support vector machine with polynomial kernel function performs best in terms of recall and F-measure rates. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Kim, IC (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6613-6 J9 P SOC PHOTO-OPT INS PY 2007 VL 6500 BP O5000 EP O5000 AR 65000O DI 10.1117/12.704423 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BGG59 UT WOS:000246686900023 ER PT S AU Zou, J Le, D Thoma, GR AF Zou, Jie Le, Daniel Thoma, George R. BE Lin, X Yanikoglu, BA TI Online medical journal article layout analysis - art. no. 65000V SO Document Recognition and Retrieval XIV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XIV CY JAN 30-FEB 01, 2007 CL San Jose, CA SP Soc Imaging Sci & Technol, SPIE DE document layout analysis; document object model (DOM); web information retrieval; HTML document segmentation; HTML document labeling; hidden Markov model; Viterbi algorithm ID DOCUMENT IMAGE-ANALYSIS; MODELS AB We describe a physical and logical layout analysis algorithm, which is applied to segment and label online medical journal articles (regular HTML and PDF-Converted-HTML files). For these articles, the geometric layout of the Web page is the most important cue for physical layout analysis. The key to physical layout analysis is then to render the HTML file in a Web browser, so that the visual information in zones (composed of one or a set of HTML DOM nodes), especially their relative position, can be utilized. The recursive X-Y cut algorithm is adopted to construct a hierarchical zone tree structure. In logical layout analysis, both geometric and linguistic features are used. The HTML documents are modeled by a Hidden Markov Model with 16 states, and the Viterbi algorithm is then used to find the optimal label sequence, concluding the logical layout analysis. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Zou, J (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 16 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6613-6 J9 P SOC PHOTO-OPT INS PY 2007 VL 6500 BP V5000 EP V5000 AR 65000V DI 10.1117/12.704434 PG 12 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BGG59 UT WOS:000246686900030 ER PT J AU Willoughby, C Fridsma, D Chatterjee, L Speakman, J Evans, J Kush, R AF Willoughby, Cara Fridsma, Doug Chatterjee, Lisa Speakman, John Evans, Julie Kush, Rebecca TI A standard computable clinical trial protocol: The role of the BRIDG model SO DRUG INFORMATION JOURNAL LA English DT Article DE protocol; clinical research; BRIDG; standard; model AB Today's clinical trial processes are inefficiently mired in excessive documentation and unnecessary human intervention. The protocol lies at the heart of these operations, making it a prime candidate for the benefits afforded by computer processing. With a vision to develop a standard machine-readable Protocol, the Protocol Representation (PR) group, a team within the Clinical Data Interchange Standards Consortium (CDISC), identified a set of elements common to regulated clinical research protocols. These elements are being incorporated into the Biomedical Research Integrated Domain Group (BRIDG) model, an information model of biomedical research initiated by CDISC and collaboratively developed and maintained by CDISC, Health Level Seven (HL7), the National Cancer Institute (NCI), the Food and Drug Administration (FDA), and other stakeholders. The PR group plans to use BRIDG as a pathway to develop a standard structured protocol representation so that protocol information can be repurposed across multiple clinical research documents, databases, and systems from study start-up through reporting and regulatory submissions. The BRIDG model provides a means of knowledge acquisition, a tool for communication, a focus for collaboration, a starting point for application development, a means to standards development and harmonization, and an informatics research platform to support clinical research. C1 CDISC, Austin, TX 78717 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Digital Infuz Inc, Gaithersburg, MD USA. NCI, Rockville, MD USA. RP Kush, R (reprint author), CDISC, 15907 2 Rivers Cove, Austin, TX 78717 USA. EM rkush@cdisc.org NR 6 TC 1 Z9 1 U1 1 U2 2 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 3 BP 383 EP 392 PG 10 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 163MY UT WOS:000246165200012 ER PT J AU Haber, MW Kisler, BW Lenzen, M Wright, LW AF Haber, Margaret W. Kisler, Bron W. Lenzen, Mary Wright, Lawrene W. TI Controlled terminology for clinical research: A collaboration between CDISC and NCI enterprise vocabulary services SO DRUG INFORMATION JOURNAL LA English DT Article DE data standards; controlled terminology; clinical research; regulatory submission; semantic interoperability ID THESAURUS AB Over the post decade, the Clinical Data Interchange Standards Consortium (CDISC) has developed international standards to improve the efficiency with which research data are collected, exchanged, and managed. The Study Data Tabulation Model (SDTM), used for regulatory submissions, is the most widely adopted CDISC standard to date. Recognizing the essential role of controlled terminology in ensuring interoperability of such standards, CDISC launched its controlled terminology initiative and has partnered with the US National Cancer Institute Enterprise Vocabulary Services to develop both the terminology and collaborative processes that con meet these needs. Completion of the controlled terminology for SDTM and building on the methods and lessons from this project will significantly advance the usefulness of CDISC data standards and move closer toward achieving full semantic interoperability. C1 NCI, Enterprise Vocabulary Serv, Rockville, MD USA. CDISC, Terminol & Strateg Alliances, Austin, TX USA. Octagon Res Solut Inc, Wayne, PA USA. RP Kisler, BW (reprint author), Heritage Pk Off Plaza,4101 Med Pkwy,Suite 202, Austin, TX 78756 USA. EM bkisler@cdisc.org NR 18 TC 3 Z9 3 U1 2 U2 3 PU DRUG INFORMATION ASSOCIATION PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2007 VL 41 IS 3 BP 405 EP 412 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 163MY UT WOS:000246165200014 ER PT J AU Gonzalez, FJ AF Gonzalez, Frank J. TI The 2006 Bernard B. Brodie Award Lecture - CYP2E1 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID INDUCED HEPATIC NECROSIS; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; OXIDIZING SYSTEM MEOS; POSTTRANSCRIPTIONAL REGULATION; MICROSOMAL CYTOCHROME-P-450; N-NITROSODIMETHYLAMINE; METABOLIC-ACTIVATION; REACTIVE METABOLITE; OXIDATIVE STRESS; DRUG-METABOLISM AB Bernard B. Brodie's laboratory was the first to examine the mechanisms of drug-induced toxicity at the molecular level. They found that acetaminophen hepatotoxicity was due to the metabolic activation of the drug to a highly reactive toxic metabolite that depleted cellular glutathione and covalently bound to protein. Subsequent studies revealed that activation of acetaminophen to an active metabolite is primarily carried out by CYP2E1, an ethanol-inducible cytochrome P450 that was first suggested by characterization of the microsomal ethanol oxidation system. CYP2E1 is developmentally regulated, under liver-specific control, and undergoes substrate-induced protein stabilization. It is also regulated by starvation and diabetes through insulin-dependent mRNA stabilization. In addition to acetaminophen, CYP2E1 metabolically activates a large number of low M-r toxicants and carcinogens and thus is of great toxicological importance. The mechanism of regulation CYP2E1 and its role in acetaminophen toxicity will be discussed. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS NR 69 TC 112 Z9 120 U1 3 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN PY 2007 VL 35 IS 1 BP 1 EP 8 DI 10.1124/dmd.106.012492 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120XF UT WOS:000243119400001 PM 17020953 ER PT J AU Lee, SJ van der Heiden, IP Goldstein, JA van Schaik, RHN AF Lee, Su-Jun van der Heiden, Ilse P. Goldstein, Joyce A. van Schaik, Ron H. N. TI A new CYP3A5 variant, CYP3A5*11, is shown to be defective in nifedipine metabolism in a recombinant cDNA expression system SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN CYTOCHROME-P450 3A4; SINGLE NUCLEOTIDE POLYMORPHISMS; SUBSTRATE RECOGNITION SITE; DRUG-METABOLISM; GENETIC-POLYMORPHISM; DOSE RATIO; TACROLIMUS; ENZYMES; IDENTIFICATION; CYCLOSPORINE AB A new CYP3A5 variant, CYP3A5*11, was found in a white European subject by DNA sequencing. The CYP3A5*11 allele contains a single nucleotide polymorphism (SNP) (g.3775A > G) in exon 2, which results in a Tyr53Cys substitution, and a g.6986A > G splice change, the latter SNP previously reported in the defective CYP3A5*3 allele. However, the CYP3A5*3 is not a null allele because this variant is associated with leaky splicing, resulting in small amounts of functional protein still being produced. Therefore, we constructed a cDNA coding for the newly identified CYP3A5.11 protein by site-directed mutagenesis, expressed it in Escherichia coli, and partially purified it. Whereas bacteria transformed with wild-type CYP3A5*1 cDNA expressed predominantly cytochrome P450 (P450), those transfected with CYP3A5*11 expressed a significant amount of denatured cytochrome P420 in addition to P450, suggesting the protein to be unstable. CYP3A5.11 exhibited a 38% decrease in the V-max for nifedipine metabolism, a 2.7-fold increase in the K-m, and a 4.4-fold decrease in the CLint of nifedipine compared with CYP3A5.1. A polymerase chain reaction-restriction fragment length polymorphism genotyping procedure was developed and used to genotype DNA of 500 white individuals for CYP3A5*11. No additional examples of this allele were identified. In summary, individuals carrying the rare CYP3A5*11 allele are predicted to have lower metabolism of CYP3A5 substrates than individuals expressing CYP3A5*3. C1 Erasmus MC, Dept Clin Chem, NL-3000 CA Rotterdam, Netherlands. NIEHS, Human Metab Sect,Dept Hlth & Human Serv, Lab Pharmacol & Chem, Natl Inst Environm Hlth Sci,NIH, Res Triangle Pk, NC 27709 USA. RP van Schaik, RHN (reprint author), Erasmus MC, Dept Clin Chem, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM r.vanschaik@erasmusmc.nl RI Goldstein, Joyce/A-6681-2012 FU Intramural NIH HHS [Z01 ES021024-27] NR 39 TC 7 Z9 9 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN PY 2007 VL 35 IS 1 BP 67 EP 71 DI 10.1124/dmd.106.012310 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120XF UT WOS:000243119400010 PM 17035598 ER PT J AU Medina-Diaz, IM Arteaga-Illan, G de Leon, MB Cisneros, B Sierra-Santoyo, A Vega, L Gonzalez, FJ Elizondo, G AF Medina-Diaz, Irma M. Arteaga-Illan, Georgina de Leon, Mario Bermudez Cisneros, Bulmaro Sierra-Santoyo, Adolfo Vega, Libia Gonzalez, Frank J. Elizondo, Guillermo TI Pregnane X receptor-dependent induction of the CYP3A4 gene by o,p '-1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN HEPATOCYTES; HUMAN LIVER; BREAST-CANCER; IN-VITRO; EXPRESSION; CYTOCHROME-P450; METABOLISM; DDT; RAT; PESTICIDES AB CYP3A4, the predominant cytochrome P450 (P450) expressed in human liver and intestine, contributes to the metabolism of approximately half the drugs in clinical use today. CYP3A4 catalyzes the 6 beta-hydroxylation of a number of steroid hormones and is involved in the bioactivation of environmental procarcinogens. The expression of CYP3A4 is affected by several stimuli, including environmental factors such as insecticides and pesticides. The o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) isomer of DDT comprises approximately 20% of technical grade DDT, which is an organochloride pesticide. We have recently shown that o,p'-DDT exposure increases CYP3A4 mRNA levels in HepG2 cells. To determine the mechanism by which o,p'-DDT induces CYP3A4 expression, transactivation and electrophoretic mobility shift assays were carried out, revealing that o,p'-DDT activates the CYP3A4 gene promoter through the pregnane X receptor (PXR). CYP3A4 gene promoter activation resulted in both an increase in CYP3A4 mRNA levels and an increase in the total CYP3A4 activity in HepG2 cells. We also observed induction of CYP3A4 and mouse Cyp3a11 mRNA in the intestine of CYP3A4-transgenic mice after exposure to 1 mg/kg o,p'-DDT. At higher doses, a decrease of CYP3A4 inducibility was observed together with an increase in levels of interleukin 6 mRNA, a proinflammatory cytokine that strongly represses CYP3A4 transcription. The present study indicates that regulation of other genes under PXR control may be altered by o,p'-DDT exposure. C1 Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Toxicol Sect, Mexico City 07000, DF, Mexico. Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Genet & Mol Biol, Mexico City 07000, DF, Mexico. Autonomous Univ Nayarit, Lab Environm & Toxicol Anal, Nayarit, Mexico. NIH, Met Lab, NCI, Bethesda, MD 20892 USA. RP Elizondo, G (reprint author), POB 14-740, Mexico City 07000, DF, Mexico. EM gazuela@cinvestav.mx RI Vega, Libia/C-3391-2013 OI Vega, Libia/0000-0002-4993-5267 NR 40 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN PY 2007 VL 35 IS 1 BP 95 EP 102 DI 10.1124/dmd.106.011759 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120XF UT WOS:000243119400014 PM 17035600 ER PT J AU Gonzalez, FJ AF Gonzalez, Frank J. TI MECHANISM OF PEROXISOME PROLIFERATOR-INDUCED HEPATOCARCINOGENESIS SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 8th Annual Meeting of the International-Society-for-Study-of-Xenobiotics CY OCT 09-12, 2007 CL Sendai, JAPAN SP Int Soc Study Xenobiot C1 [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2007 VL 39 SU 1 MA 1 BP 1 EP 1 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 670RD UT WOS:000283444100002 ER PT J AU Watanabe, M Miyata, M Gonzalez, FJ Yamazoe, Y AF Watanabe, Miwa Miyata, Masaaki Gonzalez, Frank J. Yamazoe, Yasushi TI INFLUENCE OF HIGH-FAT DIET ON BODY WEIGHT AND LIPID METABOLISM IN FEMALE FXR-NULL MICE SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 8th Annual Meeting of the International-Society-for-Study-of-Xenobiotics CY OCT 09-12, 2007 CL Sendai, JAPAN SP Int Soc Study Xenobiot C1 [Watanabe, Miwa; Miyata, Masaaki; Yamazoe, Yasushi] Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi 980, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2007 VL 39 SU 1 MA 159 BP 113 EP 114 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 670RD UT WOS:000283444100154 ER PT J AU Saji, T Kikuchi, R Kusuhara, H Kim, I Gonzalez, FJ Sugiyama, Y AF Saji, Takami Kikuchi, Ryota Kusuhara, Hiroyuki Kim, Insook Gonzalez, Frank J. Sugiyama, Yuichi TI TRANSCRIPTIONAL REGULATION OF HUMAN AND MOUSE ORGANIC ANION TRANSPORTER 1 BY HEPATOCYTE NUCLEAR FACTOR 1 alpha/beta SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 8th Annual Meeting of the International-Society-for-Study-of-Xenobiotics CY OCT 09-12, 2007 CL Sendai, JAPAN SP Int Soc Study Xenobiot C1 [Saji, Takami; Kikuchi, Ryota; Kusuhara, Hiroyuki; Sugiyama, Yuichi] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Mol Pharmacokinet, Tokyo, Japan. [Kim, Insook; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2007 VL 39 SU 1 MA 198 BP 140 EP 140 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 670RD UT WOS:000283444100193 ER PT J AU Miyata, M Matsuda, Y Nomoto, M Gonzalez, FJ Yamazoe, Y AF Miyata, Masaaki Matsuda, Yoshiki Nomoto, Masahiro Gonzalez, Frank J. Yamazoe, Yasushi TI CHOLESTEROL FEEDING PREVENTS HEPATIC ACCUMULATION OF BILE ACIDS IN CHOLIC ACID-FED Fxr-NULL MICE: FXR-INDEPENDENT SUPPRESSION OF INTESTINAL BILE ACID ABSORPTION SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 8th Annual Meeting of the International-Society-for-Study-of-Xenobiotics CY OCT 09-12, 2007 CL Sendai, JAPAN SP Int Soc Study Xenobiot C1 [Miyata, Masaaki; Matsuda, Yoshiki; Nomoto, Masahiro; Yamazoe, Yasushi] Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Sendai, Miyagi 980, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2007 VL 39 SU 1 MA 239 BP 169 EP 169 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 670RD UT WOS:000283444100235 ER PT J AU Chen, C Gonzalez, FJ Idle, JR AF Chen, Chi Gonzalez, Frank J. Idle, Jeffrey R. TI LC-MS-based metabolomics in drug metabolism SO DRUG METABOLISM REVIEWS LA English DT Review DE metabolomics; xenobiotic metabolism; drug metabolism; LC-MS; multivariate data analysis ID FLIGHT MASS-SPECTROMETRY; DEBRISOQUINE SULFATE; FUNCTIONAL GENOMICS; SYSTEMS BIOLOGY; HUMANIZED LIVER; METABONOMICS; CYTOCHROME-P450; MICE; HYDROXYLATION; TOXICITY AB Xenobiotic metabolism, a ubiquitous natural response to foreign compounds, elicits initiating signals for many pathophysiological events. Currently, most widely used techniques for identifying xenobiotic metabolites and metabolic pathways are empirical and largely based oil in vitro incubation assays and in vivo radiotracing experiments. Recent work in our lab has shown that LC-MS-based metaboloinic techniques are useful tools for xenobiotic metabolisim research since multivariate data analysis in metabolomics call significantly rationalize the processes of xenobiotic metabolite identification and metabolic pathway analysis. In this review, the technological elements of LC-MS-based metabolontics for constructing high-quality datasets and conducting comprehensive data analysis are examined. Four novel approaches of using LC-MS-based metabolonmic techniques in xenobiotic metabolism research are proposed and illustrated by case studies and proof-of-concept experiments, and the perspective oil their application is further discussed. C1 NCI, Ctr Canc Res, Lab Metab, Bethesda, MD 20892 USA. Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Ctr Canc Res, Lab Metab, 37 Convent Dr, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI Chen, Chi/B-4618-2008; OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS [Z01 BC005562-19] NR 52 TC 114 Z9 121 U1 6 U2 51 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2007 VL 39 IS 2-3 BP 581 EP 597 DI 10.1080/03602530701497804 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 207HK UT WOS:000249242000027 PM 17786640 ER PT J AU Eisenhofer, G Rivers, G Rosas, AL Quezado, Z Manger, WM Pacak, K AF Eisenhofer, Graeme Rivers, Graham Rosas, Alejandro L. Quezado, Zena Manger, William M. Pacak, Karel TI Adverse drug reactions in patients with phaeochromocytoma - Incidence, prevention and management SO DRUG SAFETY LA English DT Review ID MONOAMINE-OXIDASE INHIBITOR; CLINICALLY UNSUSPECTED PHEOCHROMOCYTOMA; CATECHOLAMINE-INDUCED CARDIOMYOPATHY; DOPAMINE-SECRETING PHEOCHROMOCYTOMA; ENDOCRINE NEOPLASIA TYPE-2; ADRENAL CHROMAFFIN CELLS; MULTIPLE ORGAN FAILURE; HYPERTENSIVE CRISIS; PULMONARY-EDEMA; MALIGNANT PHEOCHROMOCYTOMA AB The dangers of phaeochromocytomas are mainly due to the capability of these neuroendocrine tumours to secrete large quantities of vasoactive catecholamines, thereby increasing blood pressure and causing other related adverse events or complications. Phaeochromocytomas are often missed, sometimes only becoming apparent during therapeutic interventions that provoke release or interfere with the disposition of catecholamines produced by the tumours. Because phaeochromocytomas are rare, evidence contraindicating use of specific drugs is largely anecdotal or based on case reports. The heterogeneous nature of the tumours also makes adverse reactions highly variable among patients. Some drugs, such as dopamine D-2 receptor antagonists (e.g. metoclopramide, veralipride) and beta-adrenergic receptor antagonists (beta-blockers) clearly carry high potential for adverse reactions, while others such as tricyclic antidepressants seem more inconsistent in producing complications. Other drugs capable of causing adverse reactions include monoamine oxidase inhibitors, sympathomimetics (e.g. ephedrine) and certain peptide and corticosteroid hormones (e.g. corticotropin, glucagon and glucocorticoids). Risks associated with contraindicated medications are easily minimised by adoption of appropriate safeguards (e.g. adrenoceptor blockade). Without such precautions, the state of cardiovascular vulnerability makes some drugs and manipulations employed during surgical anaesthesia particularly dangerous. Problems arise most often when drugs or therapeutic procedures are employed in patients in whom the tumour is not suspected. In such cases, it is extremely important for the clinician to recognise the possibility of an underlying catecholamine-producing tumour and to take the most appropriate steps to manage and treat adverse events and clinical complications. C1 Univ Dresden, Dept Med, Dept Clin Chem & Lab Med, D-01307 Dresden, Germany. Royal Hobart Hosp, Dept Pharm, Hobart, Tas, Australia. The Methodist Hosp, Dept Anaesthesiol, Houston, TX USA. NIH, Natl Inst Hlth Clin Ctr, Dept Anaesthesiol, Surg Serv, Bethesda, MD USA. NYU, Med Ctr, New York, NY USA. NIH, Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), Univ Dresden, Dept Med, Dept Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany. EM Graeme.Eisenhofer@unikhnikum-dresden.de RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS NR 294 TC 46 Z9 50 U1 0 U2 1 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2007 VL 30 IS 11 BP 1031 EP 1062 PG 32 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 232KH UT WOS:000251018100004 PM 17973541 ER PT J AU Di Lorenzo, G Autorino, R Figg, WD De Placido, S AF Di Lorenzo, Giuseppe Autorino, Riccardo Figg, William D. De Placido, Sabino TI Hormone-refractory prostate cancer - Where are we going? SO DRUGS LA English DT Article ID PHASE-II TRIAL; CHEMOTHERAPY-NAIVE PATIENTS; ANDROGEN RECEPTOR; 2ND-LINE CHEMOTHERAPY; PLUS PREDNISONE; GROWTH-FACTOR; CELL-LINES; DOCETAXEL; MITOXANTRONE; CARCINOMA AB This article addresses the current status of therapeutic options in the management of hormone-refractory prostate cancer (HRPC). Following the publication of two landmark randomised trials, docetaxel chemotherapy is now the standard of care for men with metastatic HRPC. However, the benefit of this treatment is limited. Trials are now focusing on improving the efficacy of docetaxel by combining it with novel biological agents. Several new docetaxel-based combinations are under evaluation and promising results have been found for the combination of docetaxel with angiogenesis inhibitors. Early phase III trial data for atrasentan appear interesting. New cytotoxic agents such as satraplatin and ixabepilone are being investigated in several ongoing studies in order to define their role as second-line treatments of HRPC. Vaccine therapy offers an active immunological approach for combating malignancy in a targeted manner. C1 Univ Naples Federico 2, Dept Clin & Mol Oncol, Naples, Italy. Univ Naples 2, Urol Clin, Naples, Italy. NCI, Mol Pharmacol Sect, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Di Lorenzo, G (reprint author), Univ Naples Federico 2, Cattedra Oncol Med, Dipartimento Endocrinol & Oncol Mol & Clin, Naples, Italy. EM giuseppedilorenzoncol@hotmail.com RI Figg Sr, William/M-2411-2016 NR 69 TC 14 Z9 14 U1 1 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2007 VL 67 IS 8 BP 1109 EP 1124 DI 10.2165/00003495-200767080-00002 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 181JX UT WOS:000247434100002 PM 17521214 ER PT J AU Dancey, JE AF Dancey, Janet E. TI Epidermal growth factor receptor inhibitors in non-small cell lung cancer SO DRUGS LA English DT Article ID TYROSINE KINASE INHIBITOR; GENE COPY NUMBER; PREVIOUSLY TREATED PATIENTS; PHASE-III; EGFR MUTATION; GEFITINIB SENSITIVITY; ACTIVATING MUTATIONS; ACQUIRED-RESISTANCE; FUTURE-DIRECTIONS; DOMAIN MUTATIONS AB Aberrant epidermal growth factor receptor (EGFR) signalling contributes to neoplastic transformation and EGFR inhibition by antibodies and small molecules inhibits cancer cell proliferation and survival. In previously treated patients with non-small cell lung cancer, the administration of gefitinib and erlotinib are associated with objective tumour response rates of 8-19%. However, only erlotinib has been shown definitively to improve patient survival. The likelihood of benefit may be determined by the presence of specific genotypic abnormalities in EGFR or downstream pathway components. Additional evaluation to determine optimal dose/schedule of the agents combined with standard treatments and with other targeted agents in appropriately selected patients are areas of active research. C1 NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. RP Dancey, JE (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Room 7131,6130 Execut Blvd, Rockville, MD 20852 USA. EM danceyj@ctep.nci.nih.gov RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 83 TC 11 Z9 12 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2007 VL 67 IS 8 BP 1125 EP 1138 DI 10.2165/00003495-200767080-00003 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 181JX UT WOS:000247434100003 PM 17521215 ER PT J AU Oldfield, V Keating, GM Perry, CM AF Oldfield, Vicki Keating, Gillian M. Perry, Caroline M. TI Rasagiline - A review of its use in the management of Parkinson's disease SO DRUGS LA English DT Review ID MONOAMINE-OXIDASE-B; MPTP-INDUCED NEUROTOXICITY; QUALITY-OF-LIFE; MAO-B; MOTOR FLUCTUATIONS; DOUBLE-BLIND; IN-VIVO; CONTROLLED-TRIAL; ADJUNCTIVE THERAPY; POTENT INHIBITOR AB Rasagiline (Azilects (R)) is a novel, selective, irreversible second-generation inhibitor of monoamine oxidase type B (MAO-B). It is administered orally once daily and is approved in the US, Canada, Mexico, Israel and the EU for use as monotherapy and as adjunct therapy in the treatment of Parkinson's disease. Results of well designed clinical studies indicate that rasagiline is effective as initial monotherapy and improves Parkinson's symptomatology in patients with early Parkinson's disease. In addition, when administered in conjunction with levodopa, in patients with moderate to advanced disease and motor fluctuations, rasagiline reduces mean daily 'off' time and increases daily 'on' time without troublesome dyskinesias, compared with controls. Rasagiline is generally well tolerated as monotherapy and adjunctive therapy and is administered once daily. Thus, rasagiline, administered as a simple and convenient dosage regimen, is a well tolerated and effective option for monotherapy in patients with early Parkinson's disease and for adjunctive therapy in patients with moderate to advanced disease. Rasagiline selectively and irreversibly inhibited MAO-B activity in a number of Properties in vitro and in vivo studies. It was 5- to 10-fold more potent than selegiline at inhibiting MAO-B activity in rats. The inhibition of MAO-B activity by rasagiline is thought to lead to an increase in striatal extracellular dopamine levels and may account for the beneficial effect of rasagiline treatment on motor function observed in animal models of Parkinson's disease. Rasagiline has demonstrated neuroprotective activity in animal studies and in vitro. Its main metabolite, 1-(R)-aminoindan has shown beneficial effects in vitro and in vivo and does not inhibit the anti-apoptotic activity of rasagiline and has no sympathomimetic effects, unlike the major selegiline metabolites, L-amphetamine (L-amfetamine) and L-methamphetamine (L-metamfetamine), which are neurotoxic and inhibit the neuroprotective activity of the parent drug. In humans, oral rasagiline is rapidly absorbed, reaching a maximum plasma concentration (C-max) in <= 0.7 hours. Log C-max was significantly correlated with the percentage of platelet MAO-B inhibition in healthy volunteers. Rasagiline undergoes extensive hepatic metabolism, with less than 1% of the dose being eliminated in the urine unchanged. The main metabolites are 1-(R)-aminoindan, 3-hydroxy-N-propargyl-1-aminoindan and 3-hydroxy-1-aminoindan. Cmax and the area under the plasma concentration-time curve increased by 2-fold and 7-fold, respectively, in patients with moderate hepatic impairment (Child-Pugh score 7-9) compared with healthy individuals, following repeat dose administration for 7 days. The pharmacokinetic parameters of rasagiline in patients with mild or moderate renal impairment are similar to those observed in healthy volunteers. The therapeutic efficacy of oral once-daily rasagiline has been evaluated in three large well designed clinical trials. Patients with early Parkinson's disease received rasagiline as early initial monotherapy in the TEMPO trial, which was designed to evaluate the efficacy of rasagiline prior to treatment with dopaminergic agents including levodopa. In the PRESTO and LARGO trials, patients with moderate to advanced disease and motor fluctuations received rasagiline as an adjunct to levodopa plus a dopa decarboxylase inhibitor. C1 Med Univ Ohio, Dept Neurol, Toledo, OH USA. Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10027 USA. Natl Inst Longev Sci, Obu, Aichi, Japan. Inst Appl Biochem, Dept Brain Sci, Gifu, Japan. NINDS, Neurosci Ctr, Rockville, MD USA. RP Perry, CM (reprint author), 41 Centorian Dr,Private Bag 65901,Mairangi Bay,N, Auckland 0754, New Zealand. EM demail@adis.co.nz NR 101 TC 30 Z9 30 U1 2 U2 13 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2007 VL 67 IS 12 BP 1725 EP 1747 DI 10.2165/00003495-200767120-00006 PG 23 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 210HZ UT WOS:000249448600007 PM 17683172 ER PT J AU Ludlow, CL Humbert, I Saxon, K Poletto, C Sonies, B Crujido, L AF Ludlow, Christy L. Humbert, Ianessa Saxon, Keith Poletto, Christopher Sonies, Barbara Crujido, Lisa TI Effects of surface electrical stimulation both at rest and during swallowing in chronic pharyngeal dysphagia SO DYSPHAGIA LA English DT Article DE deglutition; deglutition disorders; hyolaryngeal movement; aspiration; penetration; sensory stimulation; resistance; transcutaneous neuromuscular stimulation ID BEHAVIOR AB We tested two hypotheses using surface electrical stimulation in chronic pharyngeal dysphagia: that stimulation (1) lowered the hyoid bone and/or larynx when applied at rest, and (2) increased aspiration, penetration, or pharyngeal pooling during swallowing. Bipolar surface electrodes were placed on the skin overlying the submandibular and laryngeal regions. Maximum tolerated levels of stimulation were applied while patients held their mouth closed at rest. Videofluoroscopic recordings were used to measure hyoid movements in the superior-inferior and anterior-posterior dimensions and the subglottic air column position while stimulation was on or off. Patients swallowed 5 ml liquid when stimulation was off, at low sensory stimulation levels, and at maximum tolerated levels (motor). Speech pathologists, blinded to condition, tallied the frequency of aspiration, penetration, pooling, and esophageal entry from videofluorographic recordings of swallows. Only significant (p = 0.0175) hyoid depression occurred during stimulation at rest. Aspiration and pooling were significantly reduced only with low sensory threshold levels of stimulation (p = 0.025) and not during maximum levels of surface electrical stimulation. Those patients who had reduced aspiration and penetration during swallowing with stimulation had greater hyoid depression during stimulation at rest (p = 0.006). Stimulation may have acted to resist patients' hyoid elevation during swallowing. C1 NINDS, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Med, GRECC, Madison, WI USA. Univ Wisconsin, Dept Radiol, GRECC, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NIH, Dept Rehabil, Ctr Clin, Bethesda, MD 20892 USA. Arizona State Univ, Dept Speech & Hearing Sci, Tempe, AZ USA. RP Ludlow, CL (reprint author), 10 Ctr Dr MSC 1416 Bldg,10 Rm,5D38, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS; NINDS NIH HHS [Z01 NS 02980, Z01 NS002980, Z01 NS002980-08] NR 15 TC 91 Z9 114 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD JAN PY 2007 VL 22 IS 1 BP 1 EP 10 DI 10.1007/s00455-006-9029-4 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 132SN UT WOS:000243962600001 PM 16718620 ER PT J AU Rottman, JN Ni, GM Brown, M AF Rottman, Jeffrey N. Ni, Gemin Brown, Michael TI Echocardiographic evaluation of ventricular function in mice SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE ventricular function; murine echocardiography; anesthesia effects ID POSITRON-EMISSION-TOMOGRAPHY; GENETICALLY ALTERED MICE; MAGNETIC-RESONANCE; CARDIAC-FUNCTION; DIASTOLIC FUNCTION; HEART-FAILURE; ANESTHETIZED MICE; HIGH-RESOLUTION; MOUSE; SYSTEM AB Ventricular dysfunction remains a hallmark of most cardiac disease. The mouse has become an essential model system for cardiovascular biology, and echocardiography an established tool in the study of normal and genetically altered mice. This review describes the measurement of ventricular function, most often left ventricular function, by echocardiographic methods in mice. Technical limitations related to the small size and rapid heart rate in the mouse initially argued for the performance of echocardiography under anesthesia. More recently, higher frame rates and smaller probes operating at higher frequencies have facilitated imaging of conscious mice in some, but not all, experimental protocols and conditions. Ventricular function may be qualitatively and quantitatively evaluated under both conditions. Particular detail is provided for measurement under conscious conditions, and measurement under conscious and sedated or anesthestized conditions are contrasted. Normal values for echocardiographic indices for the common C57BL/6 strain are provided. Diastolic dysfunction is a critical pathophysiologic component of many disease states, and progress in the echocardiographic evaluation of diastolic function is discussed. Finally, echocardiography exists among several competing imaging technologies, and these alternatives are compared. (ECHOCARDIOGRAPHY, Volume 24, January 2007) C1 Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Dept Internal Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. Meharry Med Coll, Nashville, TN USA. RP Rottman, JN (reprint author), Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Dept Internal Med, 371 PRB,2220 Pierce Ave, Nashville, TN 37232 USA. EM jeff.rottman@vanderbilt.edu FU NIDDK NIH HHS [U24 DK-59637] NR 56 TC 51 Z9 57 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JAN PY 2007 VL 24 IS 1 BP 83 EP 89 DI 10.1111/j.1540-8175.2006.00356.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 122NP UT WOS:000243234000016 PM 17214630 ER PT J AU Palacios, G Quan, PL Jabado, OJ Conlan, S Hirschberg, DL Liu, Y Zhai, J Renwick, N Hui, J Hegyi, H Grolla, A Strong, JE Towner, JS Geisbert, TW Jahrling, PB Buechen-Osmond, C Ellerbrok, H Sanchez-Seco, MP Lussier, Y Formenty, P Nichol, ST Feldmann, H Briese, T Lipkin, WI AF Palacios, Gustavo Quan, Phenix-Lan Jabado, Omar J. Conlan, Sean Hirschberg, David L. Liu, Yang Zhai, Junhui Renwick, Neil Hui, Jeffrey Hegyi, Hedi Grolla, Allen Strong, James E. Towner, Jonathan S. Geisbert, Thomas W. Jahrling, Peter B. Buechen-Osmond, Cornelia Ellerbrok, Heinz Sanchez-Seco, Maria Paz Lussier, Yves Formenty, Pierre Nichol, Stuart T. Feldmann, Heinz Briese, Thomas Lipkin, W. Ian TI Panmicrobial oligonucleotide array for diagnosis of infectious diseases SO EMERGING INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; VIRAL HEMORRHAGIC FEVERS; VIRUS-INFECTION; HUMAN MONKEYPOX; PATHOGENS; CORONAVIRUS; ALIGNMENT; OUTBREAK; CONGO AB To facilitate rapid, unbiased, differential diagnosis of infectious diseases, we designed GreeneChipPm, a panmicrobial microarray comprising 29,455 sixty-mer oligonucleotide probes for vertebrate viruses, bacteria, fungi, and parasites. Methods for nucleic acid preparation, random primed PCR amplification, and labeling were optimized to allow the sensitivity required for application with nucleic acid extracted from clinical materials and cultured isolates. Analysis of nasopharyngeal aspirates, blood, urine, and tissue from persons with various infectious diseases confirmed the presence of viruses and bacteria identified by other methods, and implicated Plasmodium falciparum in an unexplained fatal case of hemorrhagic feverlike disease during the Marburg hemorrhagic fever outbreak in Angola in 2004-2005. C1 Columbia Univ, Jerome L & Dawn Greene Infect Dis Lab, Mailman Sch Publ Hlth, New York, NY 10032 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Chicago, Chicago, IL 60637 USA. Inst Enzymol, Budapest, Hungary. Publ Hlth Agcy Canada, Winnipeg, MB, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Natl Inst Hlth, Integrated Res Facil, Ft Detrick, MD 21702 USA. Robert Koch Inst, D-1000 Berlin, Germany. Inst Salud Carlos III, Madrid, Spain. World Hlth Org, Geneva, Switzerland. Univ Manitoba, Winnipeg, MB, Canada. RP Lipkin, WI (reprint author), Columbia Univ, Jerome L & Dawn Greene Infect Dis Lab, Mailman Sch Publ Hlth, 722 W 168th St,Rm 1801, New York, NY 10032 USA. EM wil2001@columbia.edu RI Jabado, Omar/B-3406-2008; Palacios, Gustavo/I-7773-2015; OI Palacios, Gustavo/0000-0001-5062-1938; Lussier, Yves/0000-0001-9854-1005 FU NIAID NIH HHS [AI056118, AI51292, AI55466, R01 AI051292, R21 AI055466, R21 AI056118, U01 AI070411, U01AI070411, U54 AI057158, U54AI57158]; NLM NIH HHS [K22 LM008308, K22 LM008308-04] NR 24 TC 187 Z9 198 U1 1 U2 8 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2007 VL 13 IS 1 BP 73 EP 81 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 128XH UT WOS:000243692500011 PM 17370518 ER PT J AU Nordstrand, A Bunikis, I Larsson, C Tsogbe, K Schwan, TG Nilsson, M Bergstrom, S AF Nordstrand, Annika Bunikis, Ignas Larsson, Christer Tsogbe, Kodjo Schwan, Tom G. Nilsson, Mikael Bergstrom, Sven TI Tickborne relapsing fever diagnosis obscured by malaria, Togo SO EMERGING INFECTIOUS DISEASES LA English DT Article ID TICK-BORNE BORRELIOSIS; WEST-AFRICA; ANTIGENIC VARIATION; CROCIDURAE; INFECTIONS; DNA AB Given the prevalence of relapsing fever (RF) in Senegal, this disease may cause illness and death in other areas of West Africa. We performed a cross-sectional, clinic-based study to investigate the presence of RF in Togo during 2002-2004. Blood samples from patients with fever were examined for RF spirochetes by microscopy, PCR, and DNA sequencing of amplicons and for antibodies to the glycerophosphodiester phosphodiesterase antigen. Although no spirochetes were seen in blood smears, approximate to 10% of the patients were positive by PCR and approximate to 13% were seropositive for spirochetes. DNA sequencing demonstrated that Borrelia crocidurae and B. duttonii were present. Most patients were treated for malaria whether or not plasmodia were observed. Thus, many RF patients originally had a misdiagnosis of malaria, which resulted in ineffective treatment. The inability of microscopic analysis to detect spirochetes compared with PCR demonstrates the need for tests with greater sensitivity. C1 Umea Univ, Dept Mol Biol, SE-90187 Umea, Sweden. Assoc Protestane Oeuvres Medicosociales & Humanit, Lome, Togo. Natl Inst Hlth, Hamilton, MT USA. Swedish Inst Infect Dis Control, Solna, Sweden. RP Bergstrom, S (reprint author), Umea Univ, Dept Mol Biol, SE-90187 Umea, Sweden. EM sven.bergstrom@molbiol.umu.se NR 22 TC 37 Z9 38 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2007 VL 13 IS 1 BP 117 EP 123 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 128XH UT WOS:000243692500017 PM 17370524 ER PT S AU Suguitan, AL Subbarao, K AF Suguitan, Amorsolo L., Jr. Subbarao, Kanta BE Tabor, E TI The Pandemic Threat of Avian Influenza Viruses SO EMERGING VIRUSES IN HUMAN POPULATIONS SE Perspectives in Medical Virology LA English DT Article; Book Chapter ID A H5N1 VIRUS; RECEPTOR-BINDING PROPERTIES; 1918 SPANISH INFLUENZA; SINGLE AMINO-ACID; NEURAMINIDASE INHIBITOR OSELTAMIVIR; RANDOMIZED CONTROLLED-TRIAL; TO-HUMAN TRANSMISSION; HEALTH-CARE WORKERS; HONG-KONG; SOUTHEASTERN CHINA C1 [Suguitan, Amorsolo L., Jr.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Suguitan, AL (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 212 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-7069 BN 978-0-08-046790-0 J9 PERSP MED V JI Perspect. Med. Virol. PY 2007 VL 16 BP 97 EP 132 DI 10.1016/S0168-7069(06)16005-X PG 36 WC Virology SC Virology GA BCR90 UT WOS:000311223400005 ER PT S AU Lai, CJ Putnak, R AF Lai, Ching-Juh Putnak, Robert BE Tabor, E TI Dengue and the Dengue Viruses SO EMERGING VIRUSES IN HUMAN POPULATIONS SE Perspectives in Medical Virology LA English DT Article; Book Chapter ID TICK-BORNE ENCEPHALITIS; NEUTRALIZING ANTIBODY-RESPONSE; PERIPHERAL-BLOOD LEUKOCYTES; IMMUNOGLOBULIN G1 ANTIBODY; CHIMPANZEE FAB FRAGMENTS; TYPE-4 VACCINE CANDIDATE; FLAVIVIRUS GENOMIC RNA; PRIMARY KIDNEY-CELLS; RHESUS LUNG-CELLS; FULL-LENGTH CDNA C1 [Lai, Ching-Juh] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Putnak, Robert] Walter Reed Army Inst Res, Div Communicable Dis & Immunol, Dept Virus Dis, Silver Spring, MD 20910 USA. RP Lai, CJ (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 211 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-7069 BN 978-0-08-046790-0 J9 PERSP MED V JI Perspect. Med. Virol. PY 2007 VL 16 BP 269 EP 298 DI 10.1016/S0168-7069(06)16011-5 PG 30 WC Virology SC Virology GA BCR90 UT WOS:000311223400011 ER PT J AU Blair, RJR AF Blair, R. James R. BA Farrow, TFD Woodruff, PWR BF Farrow, TFD Woodruff, PWR TI Empathic dysfunction in psychopathic individuals SO EMPATHY IN MENTAL ILLNESS LA English DT Article; Book Chapter ID FEARFUL EXPRESSIONS; FACIAL EXPRESSIONS; ASPERGER-SYNDROME; DISTRESS CUES; NORMAL ADULTS; MIND; EMOTION; RECOGNITION; CHILDREN; TENDENCIES C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, 15 K North Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. NR 49 TC 15 Z9 15 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52184-734-6 PY 2007 BP 3 EP 16 D2 10.1017/CBO9780511543753 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BXW61 UT WOS:000297330300002 ER PT J AU Cowin, PA Foster, PMD Risbridger, GP AF Cowin, Prue A. Foster, Paul M. D. Risbridger, Gail P. BA Gore, AC BF Gore, AC TI Endocrine Disruption in the Male SO ENDOCRINE-DISRUPTING CHEMICALS: FROM BASIC RESEARCH TO CLINICAL PRACTICE SE Contemporary Endocrinology Series LA English DT Article; Book Chapter ID IN-UTERO EXPOSURE; ANDROGEN RECEPTOR EXPRESSION; UROGENITAL SINUS MESENCHYME; STROMAL-EPITHELIAL INTERACTIONS; NEONATAL ESTROGEN EXPOSURE; MALE REPRODUCTIVE-TRACT; RAT VENTRAL PROSTATE; EPIGENETIC TRANSGENERATIONAL ACTIONS; DUCTAL BRANCHING MORPHOGENESIS; ALTERED GENE-EXPRESSION C1 [Cowin, Prue A.; Risbridger, Gail P.] Monash Univ, Monash Inst Med Res, Ctr Urol Res, Clayton, Vic, Australia. [Foster, Paul M. D.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Cowin, PA (reprint author), Monash Univ, Monash Inst Med Res, Ctr Urol Res, Clayton, Vic, Australia. RI Risbridger, Gail/B-8655-2008 OI Risbridger, Gail/0000-0003-3089-4028 NR 193 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-59745-107-9 J9 CONTEMP ENDOCRINOL S PY 2007 BP 33 EP 62 DI 10.1007/1-59745-107-X_3 D2 10.1007/1-59745-107-X PG 30 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BNF96 UT WOS:000274470500003 ER PT J AU Armstrong, DL AF Armstrong, David L. BA Gore, AC BF Gore, AC TI Implications of Thyroid Hormone Signaling Through the Phosphoinositide-3 Kinase for Xenobiotic Disruption of Human Health SO ENDOCRINE-DISRUPTING CHEMICALS: FROM BASIC RESEARCH TO CLINICAL PRACTICE SE Contemporary Endocrinology Series LA English DT Article; Book Chapter ID ENVIRONMENTAL CHEMICALS; HIPPOCAMPAL NEUROGENESIS; VENTRICULAR MYOCYTES; POTASSIUM CHANNEL; MOLECULAR-BASIS; RHO-GTPASES; ALS2 GENE; RAC; ACTIVATION; RECEPTORS C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Armstrong, DL (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 64 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-59745-107-9 J9 CONTEMP ENDOCRINOL S PY 2007 BP 190 EP 199 D2 10.1007/1-59745-107-X PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BNF96 UT WOS:000274470500008 ER PT J AU Giacobini, P Wray, S AF Giacobini, Paolo Wray, Susan TI Cholecystokinin directly inhibits neuronal activity of primary gonadotropin-releasing hormone cells through cholecystokinin-1 receptor SO ENDOCRINOLOGY LA English DT Article ID ANTEROVENTRAL PERIVENTRICULAR NUCLEUS; EMBRYONIC OLFACTORY PLACODE; CENTRAL-NERVOUS-SYSTEM; MEDIAL PREOPTIC AREA; LHRH NEURONS; EXPLANT CULTURES; RAT-BRAIN; PARAVENTRICULAR NUCLEUS; RHESUS-MONKEY; GNRH NEURONS AB Pulsatile secretion of GnRH-1 regulates gonadotropin release from anterior pituitary and thus is essential for reproduction. The present study focused on the role of cholecystokinin ( CCK) in the GnRH-1 system. CCK is a neuropeptide abundantly expressed in the brain, which is implicated in activation of female reproductive behaviors and release of anterior pituitary hormones. Using dual-label immunocytochemistry coupled to confocal analysis, GnRH-1 neurons in adult mouse brain were found to express CCK-1 receptors ( CCK-1R), and CCK fibers were detected contacting GnRH-1 axons. To address the function of CCK on GnRH-1 neurons, calcium imaging was used to monitor patterns of activity of GnRH-1 neurons maintained in an in vitro system known to retain many characteristics of GnRH-1 cells in vivo. Endogenous receptors for CCK( CCK-1R and CCK-2R) were blocked with selective antagonists. Results indicate that CCK-1R but not CCK-2R antagonist treatment increased the number of calcium peaks/GnRH-1 cell, mean peak amplitude, and percentage of GnRH-1 cells displaying high activity. The increased activity in GnRH-1 neurons observed after application of CCK-1R antagonist was blocked by coincubation with exogenous CCK. This study provides evidence that CCK acts directly on GnRH-1 neurons to attenuate GnRH-1 neuronal activity via CCK-1R activation. C1 NINDS, Cellular & Dev Neurol Sect, NIH, Bethesda, MD 20892 USA. Univ Turin, Dept Human & Anim Biol, Neurobiol Lab, I-10126 Turin, Italy. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurol Sect, NIH, Bldg 35,Room 3A-1012, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov RI Giacobini, Paolo/P-5451-2015; OI Giacobini, Paolo/0000-0002-3075-1441; wray, susan/0000-0001-7670-3915 NR 51 TC 14 Z9 14 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2007 VL 148 IS 1 BP 63 EP 71 DI 10.1210/en.2006-0758 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118IH UT WOS:000242935200009 PM 17023535 ER PT J AU Moucha, CS Renard, RL Gandhi, A Lin, SS Tuan, RS AF Moucha, Calin S. Renard, Regis L. Gandhi, Ankur Lin, Sheldon S. Tuan, Rocky S. BE Bronner, F FarachCarson, MC Mikos, AG TI Bone Allograft Safety and Performance SO ENGINEERING OF FUNCTIONAL SKELETAL TISSUES SE Topics in Bone Biology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; DONOR SITE MORBIDITY; MECHANICAL-PROPERTIES; GAMMA-IRRADIATION; SPINAL-FUSION; ILIAC CREST; BIOMECHANICAL PROPERTIES; BACTERIAL-CONTAMINATION; MUSCULOSKELETAL-TISSUE; CORTICAL BONE C1 [Moucha, Calin S.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Orthoped, Div Adult Joint Replacement, Newark, NJ 07103 USA. [Lin, Sheldon S.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Orthoped, Foot & Ankle Div, Newark, NJ 07103 USA. [Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA. RP Moucha, CS (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Orthoped, Div Adult Joint Replacement, 185 S Orange Ave, Newark, NJ 07103 USA. NR 68 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84628-366-6 J9 TOP BONE BIOL PY 2007 VL 3 BP 46 EP 54 D2 10.1007/978-1-84628-366-6 PG 9 WC Cell & Tissue Engineering; Engineering, Biomedical; Orthopedics SC Cell Biology; Engineering; Orthopedics GA BNF99 UT WOS:000274472800004 ER PT J AU Lin, YS Vermeulen, R Tsai, CH Waidyanatha, S Lan, Q Rothman, N Smith, MT Zhang, LP Shen, M Li, GL Yin, S Kim, S Rappaport, SM AF Lin, Yu-Sheng Vermeulen, Roel Tsai, Chin H. Waidyanatha, Suramya Lan, Qing Rothman, Nathaniel Smith, Martyn T. Zhang, Luoping Shen, Min Li, Guilan Yin, Songnian Kim, Sungkyoon Rappaport, Stephen M. TI Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE albumin adduct; benzene oxide; benzoquinone; nonlinear; variation ID PROTEIN ADDUCTS; HEMOGLOBIN ADDUCTS; OXIDE; 1,4-BENZOQUINONE; RATS; LEUKEMIA; CHINA; MICE; BENZOQUINONE; HYPOTHESIS AB BACKGROUND: Metabolism of benzene produces reactive electrophiles, including benzene oxide (BO), 1,4-benzoquinone (1,4-BQ), and 1,2-benzoquinone (1,2-BQ), that are capable of reacting with blood proteins to produce adducts. OBJECTIVES: The main purpose of this study was to characterize relationships between levels of albumin adducts of these electrophiles in blood and the corresponding benzene exposures in benzene-exposed and control workers, after adjusting for important covariates. Because second blood samples were obtained from a subset of exposed workers, we also desired to estimate within-person and between-person variance components for the three adducts. METHODS: We measured albumin adducts and benzene exposures in 250 benzene-exposed workers (exposure range, 0.26-54.5 ppm) and 140 control workers (exposure range < 0.01-0.53 ppm) from Tianjin, China. Separate multiple linear regression models were fitted to the logged adduct levels for workers exposed to benzene < I ppm and >= 1 ppm. Mixed-effects models were used to estimate within-person and between-person variance components of adduct levels. RESULTS: We observed nonlinear (hockey-stick shaped) exposure-adduct relationships in log-scale, with inflection points between about 0.5 and 5 ppm. These inflection points represent air concentrations at which benzene contributed marginally to background adducts derived from smoking and from dietary and endogenous sources. Adduct levels were significantly affected by the blood-collection medium (serum or plasma containing either heparin or EDTA), smoking, age, and body mass index. When model predictions of adduct levels were plotted versus benzene exposure : I ppm, we observed marked downward concavity, particularly for adducts of the benzoquinones. The between-person variance component of adduct levels increased in the order 1,2-BQ < 1,4-BQ < BO, whereas the within-person variance components of the three adducts followed the reverse order. CONCLUSIONS: Although albumin adducts of BO and the benzoquinones reflect exposures to benzene >= 1 ppm, they would not be useful biomarkers of exposure at ambient levels of benzene, which tend to be < 0.01 ppm, or in those working populations where exposures are consistently < 1 ppm. The concavity of exposure-adduct relationships is consistent with saturable metabolism of benzene at air concentrations > 1 ppm. The surprisingly large effect of the blood-collection medium on adduct levels, particularly those of the benzoquinones, should be further investigated. C1 Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. RP Rappaport, SM (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, CB 7431, Chapel Hill, NC 27599 USA. EM smr@unc.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU NIEHS NIH HHS [P30 ES001896, P30 ES010126, P30ES01896, P30ES10126, P42 ES004705, P42 ES005948, P42ES04705, P42ES05948, R01 ES006721, R01ES06721] NR 29 TC 21 Z9 23 U1 0 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 JAN PY 2007 VL 115 IS 1 BP 28 EP 34 DI 10.1289/ehp.8948 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 123ME UT WOS:000243299200028 PM 17366815 ER PT J AU Burkhart, JG AF Burkhart, James G. TI Farewell and best wishes SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Burkhart, JG (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. EM burkhart@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2007 VL 115 IS 1 BP A12 EP A12 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 123ME UT WOS:000243299200001 ER PT J AU Schwartz, DA Korach, KS AF Schwartz, David A. Korach, Kenneth S. TI Emerging research on endocrine disruptors SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Bethesda, MD USA. RP Schwartz, DA (reprint author), NIEHS, Bethesda, MD USA. EM david.schwartz@niehs.nih.gov; korach@niehs.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 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 JAN PY 2007 VL 115 IS 1 BP A13 EP A13 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 123ME UT WOS:000243299200002 ER PT J AU Taylor, KC Jackson, LW Lynch, CD Kostyniak, PJ Louis, GMB AF Taylor, Kira C. Jackson, Leila W. Lynch, Courtney D. Kostyniak, Paul J. Louis, Germaine M. Buck TI Preconception maternal polychlorinated biphenyl concentrations and the secondary sex ratio SO ENVIRONMENTAL RESEARCH LA English DT Article DE environment; fish consumption; polychlorinated biphenyls; reproductive toxicant; sex ratio ID PARENTAL HORMONE-LEVELS; NEWBORN-INFANTS; MALE/FEMALE RATIO; FEMALE RATIO; HUMAN-SERUM; BIRTH; TIME; EXPOSURE; CONCEPTION; PREGNANCY AB The secondary sex ratio is the ratio of male to female live births and historically has ranged from 102 to 106 males to 100 females. Temporal declines have been reported in many countries prompting authors to hypothesize an environmental etiology. Blood specimens were obtained from 99 women aged 24-34 prior to attempting pregnancy and quantified for 76 polychlorinated biphenyl (PCB) congeners using dual column gas chromatography with electron capture detection. Women were prospectively followed until pregnancy or 12 cycles of trying. The odds of a male birth for three PCB groupings (total, estrogenic, anti-estrogenic) controlling for maternal characteristics were estimated using logistic regression. Among the 50 women with live births and PCB data, 26 female and 24 male infants were born (ratio 0.92). After adjusting for age and body mass index, odds of a male birth were elevated among women in the second (OR = 1.29) and third (OR = 1.48) tertiles of estrogenic PCBs; odds (OR = 0.70) were reduced among women in the highest tertile of anti-estrogenic PCBs. All confidence intervals included one. The direction of the odds ratios in this preliminary study varied by PCB groupings.. supporting the need to study specific PCB patterns when assessing environmental influences on the secondary sex ratio. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Rockville, MD 20852 USA. Dept Epidemiol, Atlanta, GA 30322 USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. SUNY Buffalo, Toxicol Res Ctr, Buffalo, NY 14214 USA. RP Louis, GMB (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural NIH HHS NR 50 TC 15 Z9 15 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JAN PY 2007 VL 103 IS 1 BP 99 EP 105 DI 10.1016/j.envres.2006.04.009 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 128YX UT WOS:000243696700012 PM 16780830 ER PT J AU Elovaara, E Stockmann-Juvala, H Mikkola, J Gelboin, HV AF Elovaara, Eivor Stockmann-Juvala, Helene Mikkola, Jouni Gelboin, Harry V. TI Interactive effects of methyl tertiary-butyl ether (MTBE) and tertiary-amyl methyl ether (TAME), ethanol and some drugs: Triglyceridemia, liver toxicity and induction of CYP (2E1, 2B1) and phase II enzymes in female Wistar rats SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE gasoline oxygenates; ethanol; pyrazole; phenobarbital; acetaminophen; isotretinoin; interactive toxicity; induction of drug-metabolizing enzymes ID SPRAGUE-DAWLEY RATS; HUMAN CYTOCHROME-P450 2A6; MONOCLONAL-ANTIBODIES; ISOTRETINOIN THERAPY; GASOLINE VAPOR; METABOLISM; MICROSOMES; BIOTRANSFORMATION; HEPATOTOXICITY; EXCRETION AB The abilities of the gasoline additives methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME) to cause liver damage following oral administration, dosed alone or in combination with model hepatotoxins, were investigated in the rat. Inducibility of liver drug-metabolizing enzyme activities was also studied. Exposure to these ethers (10-20mmol/kg) for 3 days resulted in hepatomegaly (13-30%) and induction of cytochrome P450 (CYP) activity towards N-nitrosodirnethylamine (NDMAD), 7-pentoxyresorufin (PROD), and 7-ethoxyresorufin (EROD). Immunoinhibition assays with monoclonal antibodies showed that the ethers were equipotent as inducers of CYP2E1 activity (2-fold increase) but not of CYP2B1, which was elevated up to 260-fold in TAME-treated rats but only by 20-fold in MTBE rats. A slight or no modifying effect was observed on the NADPH:quinone oxidoreductase (NQO1), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UGT) activities. Alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) were elevated in blood plasma after administration of the ethers. No dramatic enhancement of liver damage could be detected by plasma enzyme analysis (ALT, AST, alkaline phosphatase, gamma-glutamyltransferase) following ether administration (13.5 mmol/kg) to rats pretreated with mildly hepatotoxic dosages of ethanol, pyrazole, phenobarbital, acetaminophen (paracetamol), or 13-cis-retinoic acid (13-cis-RA or isotretinoin). Plasma triglycerides increased in TAME-treated rats (1.7-fold) and in all 13-cisRA-treated groups (2.1-2.8-fold). The findings that MTBE and TAME exhibited a clear but differential inducing effect on two ether-metabolizing CYP forms (2E1 and 2B1) with no marked effect on phase II activities may reflect the importance of these pathways in vivo. The observation that only TAME by itself induced hypertriglyceridemia while acetaminophen- and 13-cis-RA-induced hypertriglyceridemia were aggravated by both ethers, points to differences in their effects on lipid metabolism. TAME was clearly a more potent CNS depressant than MTBE. There was no marked potentiation of drug/chemical-induced acute liver damage either by MTBE or TAME. (c) 2006 Elsevier B.V. All rights reserved. C1 Finnish Inst Occupat Hlth, FIN-00250 Helsinki, Finland. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Elovaara, E (reprint author), Finnish Inst Occupat Hlth, FIN-00250 Helsinki, Finland. EM Eivor.Elovaara@ttl.fi NR 54 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD JAN PY 2007 VL 23 IS 1 BP 64 EP 72 DI 10.1016/j.etap.2006.07.003 PG 9 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA 127TP UT WOS:000243609500009 PM 21783738 ER PT S AU Alken, M Hegde, RS AF Alken, Martina Hegde, Ramanujan S. BE Dalbey, RE Koehler, CM Tamanoi, F TI The Translocation Apparatus of the Endoplasmic Reticulum SO ENZYMES: MOLECULAR MACHINES INVOLVED IN PROTEIN TRANSPORT ACROSS CELLULAR MEMBRANES, VOL 25 SE Enzymes LA English DT Article; Book Chapter ID SIGNAL RECOGNITION PARTICLE; PROTEIN-CONDUCTING CHANNEL; MULTISPANNING MEMBRANE-PROTEIN; NASCENT SECRETORY PROTEINS; RNA-POLYMERASE-II; ER MEMBRANE; SACCHAROMYCES-CEREVISIAE; COTRANSLATIONAL TRANSLOCATION; TRANSMEMBRANE SEGMENTS; SEQUENCE RECOGNITION AB Eukaryotic proteins destined for the cell surface, extracellular space, or compartments of the secretory pathway are first translocated across or inserted into the endoplasmic reticulum (ER) membrane at sites termed translocons [1-4]. The essential feature of ER translocons is a protein-conducting channel formed by the highly conserved Sec61 complex. Together with several accessory components, the Sec61 complex recognizes translocation substrates, provides a gated conduit for transport across the membrane, and regulates access to the lipid bilayer for membrane protein integration. These combined activities endow translocons with the remarkable capacity to direct the proper biogenesis and topology for a tremendously diverse set of secretory and membrane protein substrates. How is this complex feat accomplished? In this chapter, we subdivide the protein translocation process into a series of decisive mechanistic steps taken by a substrate during its transit across or insertion into the membrane. The translocon components implicated in each step and their proposed mechanisms of action are considered with an eye toward particularly important gaps in our understanding of protein translocation into the ER. C1 [Alken, Martina; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Alken, M (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Hegde, Ramanujan/0000-0001-8338-852X NR 136 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-6047 BN 978-0-08-055216-3 J9 ENZYMES JI Enzymes PY 2007 VL 25 BP 207 EP 243 DI 10.1016/S1874-6047(07)25009-7 PG 37 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCR25 UT WOS:000311080000010 ER PT J AU Seminara, D Khoury, MJ O'Brien, TR Manolio, T Gwinn, ML Little, J T Higgins, JP Bernstein, JL Boffetta, P Bondy, M Bray, MS Brenchley, PE Buffler, PA Casas, JP Chokkalingam, AP Danesh, J Smith, GD Dolan, S Duncan, R Gruis, NA Hashibe, M Hunter, D Jarvelin, MR Malmer, B Maraganore, DM Newton-Bishop, JA Riboli, E Salanti, G Taioli, E Timpson, N Uitterlinden, AG Vineis, P Wareham, N Winn, DM Zimmern, R Ioannidis, JPA AF Seminara, Daniela Khoury, Muin J. O'Brien, Thomas R. Manolio, Teri Gwinn, Marta L. Little, Julian T Higgins, Julian P. Bernstein, Jonine L. Boffetta, Paolo Bondy, Melissa Bray, Molly S. Brenchley, Paul E. Buffler, Patricia A. Casas, Juan Pablo Chokkalingam, Anand P. Danesh, John Smith, George Davey Dolan, Siobhan Duncan, Ross Gruis, Nelleke A. Hashibe, Mia Hunter, David Jarvelin, Marjo-Riitta Malmer, Beatrice Maraganore, Demetrius M. Newton-Bishop, Julia A. Riboli, Elio Salanti, Georgia Taioli, Emanuela Timpson, Nic Uitterlinden, Andre G. Vineis, Paolo Wareham, Nick Winn, Deborah M. Zimmern, Ron Ioannidis, John P. A. CA Human Genome Epidemiology Network Network Investigator Networks TI The emergence of networks in human genome epidemiology - Challenges and opportunities SO EPIDEMIOLOGY LA English DT Article ID GENETIC EPIDEMIOLOGY; BREAST-CANCER; WIDE ASSOCIATION; FAMILY REGISTRY; MUTATIONS; DISEASES; FALSE C1 NCI, Epidemiol & Genet Res Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Off Genom & Dis Prevent, Atlanta, GA USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Ottawa, Dept Epidemiol & Community Med, Canada Res Chair Human Genome Epidemiol, Ottawa, ON, Canada. Univ Cambridge, MRC, Biostat Unit, Cambridge, England. Strangeways Res Lab, Publ Hlth Genet Unit, Cambridge CB1 4RN, England. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Int Agcy Res Canc, F-69372 Lyon, France. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, Ctr Human Genet, Inst Mol Med, Houston, TX USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Royal Infirm, Renal Res Labs, Manchester Inst Nephrol & Transplantat, Manchester, Lancs, England. Univ Calif Berkeley, Berkeley, CA 94720 USA. London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England. Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. Univ Bristol, Dept Social Med, Bristol, Avon, England. Albert Einstein Coll Med, Bronx, NY 10467 USA. WHO, CH-1211 Geneva, Switzerland. Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. Univ Oulu, Dept Publ Hlth Sci & Gen Practice, Oulu, Finland. Univ Umea Hosp, Dept Radiat Sci, S-90185 Umea, Sweden. Mayo Clin, Dept Neurol, Rochester, MN USA. CR UK Clin Ctr, Genet Epidemiol Div, Leeds, W Yorkshire, England. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands. ISI Fdn, Turin, Italy. Elsie Widdowson Lab, MRC, Epidemiol Unit, Cambridge, England. Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Seminara, D (reprint author), NCI, Epidemiol & Genet Res Branch, Div Canc Control & Populat Sci, NIH, EPN Bldg,Rm 5142,MSC 7393,6130 Execut Blvd, Bethesda, MD 20892 USA. EM seminard@mail.nih.gov RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Fox, Laura /C-6249-2016; OI Higgins, Julian/0000-0002-8323-2514; Monsalve, Beatriz Elena/0000-0002-5994-866X; Brenchley, Paul/0000-0003-1290-9919; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Newton Bishop, Julia/0000-0001-9147-6802; Timpson, Nicholas/0000-0002-7141-9189 FU Intramural NIH HHS; Medical Research Council [G0600705, MC_U105285807, MC_U106179471] NR 42 TC 60 Z9 60 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2007 VL 18 IS 1 BP 1 EP 8 DI 10.1097/01.ede.0000249540.17855.b7 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 116XI UT WOS:000242836700001 PM 17179752 ER PT J AU Hoover, RN AF Hoover, Robert N. TI The evolution of epidemiologic research from cottage industry to "big" science SO EPIDEMIOLOGY LA English DT Article ID HUMAN BLADDER-CANCER; ARTIFICIAL SWEETENERS; ENVIRONMENT; COHORT; BREAST; GENES C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20852 USA. RP Hoover, RN (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8094, Bethesda, MD 20852 USA. EM hooverr@mail.nih.gov NR 12 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2007 VL 18 IS 1 BP 13 EP 17 DI 10.1097/01.ede.0000249532.81073.b2 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 116XI UT WOS:000242836700003 PM 17179754 ER PT J AU Huang, L Pickle, LW Stinchcomb, D Feuer, EJ AF Huang, Lan Pickle, Linda W. Stinchcomb, David Feuer, Eric J. TI Detection of spatial clusters - Application to cancer survival as a continuous outcome SO EPIDEMIOLOGY LA English DT Article ID LUNG-CANCER; NONPARAMETRIC-ESTIMATION; CHEMOTHERAPY AB In this article, we develop the first detailed illustration of the use of a cluster detection method using a spatial scan statistic based on an exponential survival model. We use this approach to study the spatial patterns of survival of patients with stage III or stage IV colorectal cancer or with stage I/II, stage III, or stage IV lung cancer in the State of California and the County of Los Angeles (LA) diagnosed during 1988 through 2002. We present the location of the detected clusters of short survival or long survival and compute nonparametric estimates of survival inside and outside of those detected clusters confirming the survival pattern detected by the spatial scan statistic in both areas. In LA County, we investigate the possible relationship between the cluster locations and race, sex, and histology using nonparametric methods, and we compare socioeconomic factors such as education, employment, income, and health insurance inside and outside of the detected clusters. Finally, we evaluate the effect of related covariates on statistically significant long and short survival clusters detected in LA County using logistic regression models. This article illustrates a new way to understand survival patterns that may point to health disparities in terms of diagnosis and treatment patterns. C1 NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Rockville, MD USA. RP Huang, L (reprint author), 6116 Execut Blvd,Room 5043, Rockville, MD 20852 USA. EM huangla@mail.nih.gov NR 36 TC 12 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2007 VL 18 IS 1 BP 73 EP 87 DI 10.1097/01.ede.0000249994.30736.24 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 116XI UT WOS:000242836700014 PM 17179759 ER PT J AU Theodore, W AF Theodore, W. TI 18F-FCWAY 5HT1A receptor imaging, depression, and epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 27th International Epilepsy Congress CY JUL 08-12, 2007 CL Singapore, SINGAPORE SP Int League Against Epilepsy, Int Bur Epilepsy C1 [Theodore, W.] Natl Inst Hlth, Bethesda, MD USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2007 VL 48 SU 7 BP 4 EP 4 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 274CF UT WOS:000253978700013 ER PT J AU Theodore, W AF Theodore, W. TI Introduction: Imaging serotonergic neurotransmission in epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 27th International Epilepsy Congress CY JUL 08-12, 2007 CL Singapore, SINGAPORE SP Int League Against Epilepsy, Int Bur Epilepsy C1 [Theodore, W.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2007 VL 48 SU 7 BP 4 EP 4 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 274CF UT WOS:000253978700012 ER PT J AU Shamim, S Lim, Y Liew, C Theodore, W Ostuni, J Sato, S AF Shamim, S. Lim, Y. Liew, C. Theodore, W. Ostuni, J. Sato, S. TI Magnetoencephalography and quantitative FDG-PET co-localisation SO EPILEPSIA LA English DT Meeting Abstract CT 27th International Epilepsy Congress CY JUL 08-12, 2007 CL Singapore, SINGAPORE SP Int League Against Epilepsy, Int Bur Epilepsy C1 [Shamim, S.; Sato, S.] NINDS, NIH, EG Sect, Bethesda, MD 20892 USA. [Lim, Y.; Liew, C.; Theodore, W.] NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Ostuni, J.] NINDS, NIH, ITP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2007 VL 48 SU 7 BP 68 EP 68 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 274CF UT WOS:000253978700247 ER PT J AU Bruzzo, A Gesierich, B Rubboli, G Birbaumer, N Tassinari, CA AF Bruzzo, A. Gesierich, B. Rubboli, G. Birbaumer, N. Tassinari, C. A. TI Predicting epileptic seizures by a behavioural task SO EPILEPSIA LA English DT Meeting Abstract CT 27th International Epilepsy Congress CY JUL 08-12, 2007 CL Singapore, SINGAPORE SP Int League Against Epilepsy, Int Bur Epilepsy C1 [Bruzzo, A.] Univ Bologna, Dept Psychol, I-40126 Bologna, Italy. [Gesierich, B.] Univ Ferrara, Sect Human Physiol, Dept Biomed Sci & Adv Therapies, I-44100 Ferrara, Italy. [Bruzzo, A.; Rubboli, G.; Tassinari, C. A.] Univ Bologna, Bellaria Hosp, Dept Neurol Sci, I-40126 Bologna, Italy. [Birbaumer, N.] Univ Tubingen, Inst Med Psychol Behav Neurobiol, D-72074 Tubingen, Germany. [Birbaumer, N.] NIH, Bethlehem, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2007 VL 48 SU 7 BP 83 EP 84 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 274CF UT WOS:000253978700311 ER PT J AU Fritsch, B Stott, J Rogawski, M AF Fritsch, B. Stott, J. Rogawski, M. TI Effectiveness of a noncompetitive AMPA receptor antagonist in a mouse model of status epilepticus SO EPILEPSIA LA English DT Meeting Abstract CT 1st London Colloquium on Status Epilepticus CY APR 12-15, 2007 CL Univ Coll London, London, ENGLAND HO Univ Coll London C1 NINDS, NIH, Epilespy Res Sect, Bethesda, MD 20892 USA. EM fritschb@mail.nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2007 VL 48 SU 8 BP 104 EP 105 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 229CY UT WOS:000250780300039 ER PT J AU Cho, Y Yi, S Sohn, C Jang, Y Berl, M Theodore, W Gaillard, W AF Cho, Y. Yi, S. Sohn, C. Jang, Y. Berl, M. Theodore, W. Gaillard, W. TI Language determination by fMRI with Korean paradigms SO EPILEPSIA LA English DT Meeting Abstract CT 27th International Epilepsy Congress CY JUL 08-12, 2007 CL Singapore, SINGAPORE SP Int League Against Epilepsy, Int Bur Epilepsy C1 [Cho, Y.; Yi, S.; Sohn, C.] Keimyung Univ, Dongsan Med Ctr, Taegu, South Korea. [Jang, Y.] KyungBuk Univ Hosp, Taegu, South Korea. [Berl, M.; Gaillard, W.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Theodore, W.; Gaillard, W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2007 VL 48 SU 7 BP 133 EP 133 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 274CF UT WOS:000253978700501 ER PT J AU Munashinge, J Acosta, M Guerron, A Theodore, W AF Munashinge, J. Acosta, M. Guerron, A. Theodore, W. TI Brief seizures do not cause MRI abnormalities in rats SO EPILEPSIA LA English DT Meeting Abstract CT 27th International Epilepsy Congress CY JUL 08-12, 2007 CL Singapore, SINGAPORE SP Int League Against Epilepsy, Int Bur Epilepsy C1 [Munashinge, J.; Acosta, M.; Guerron, A.; Theodore, W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2007 VL 48 SU 7 BP 136 EP 136 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 274CF UT WOS:000253978700513 ER PT S AU Duckers, HJ Nabel, EG Serruys, PW AF Duckers, Henricus J. Nabel, Elizabeth G. Serruys, Patrick W. BE Duckers, HJ Nabel, EG Serruys, PW TI ESSENTIALS OF RESTENOSIS For the Interventional Cardiologist PREFACE SO ESSENTIALS OF RESTENOSIS: FOR THE INTERVENTIONAL CARDIOLOGIST SE Contemporary Cardiology LA English DT Editorial Material; Book Chapter C1 [Duckers, Henricus J.] Erasmus MC, Thoraxctr Rotterdam, Rotterdam, Netherlands. [Nabel, Elizabeth G.] NHGRI, Nabel Lab, Genome Technol Branch,NIH, Div Intramural Res,Natl Heart Lung & Blood Inst, Bethesda, MD 20892 USA. [Serruys, Patrick W.] Erasmus MC, Thoraxctr, Dept Cardiol, Rotterdam, Netherlands. RP Duckers, HJ (reprint author), Erasmus MC, Thoraxctr Rotterdam, Rotterdam, Netherlands. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-001-0 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2007 BP V EP V D2 10.1007/978-1-59745-001-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BLY72 UT WOS:000271458800001 ER PT S AU Ganesh, SK Nabel, EG AF Ganesh, Santhi K. Nabel, Elizabeth G. BE Duckers, HJ Nabel, EG Serruys, PW TI Proteomics and Restenosis SO ESSENTIALS OF RESTENOSIS: FOR THE INTERVENTIONAL CARDIOLOGIST SE Contemporary Cardiology LA English DT Article; Book Chapter ID GLYCATION END-PRODUCTS; RAT CAROTID ARTERIES; SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; NEOINTIMAL FORMATION; P-SELECTIN; TROPONIN-I; RECEPTOR; GROWTH; ATHEROSCLEROSIS C1 [Ganesh, Santhi K.] NHLBI, Vasc Biol Sect, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. [Nabel, Elizabeth G.] NHGRI, Nabel Lab, Genome Technol Branch,NIH, Div Intramural Res,Natl Heart Lung & Blood Inst, Bethesda, MD 20892 USA. RP Ganesh, SK (reprint author), NHLBI, Vasc Biol Sect, Cardiovasc Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-001-0 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2007 BP 175 EP 183 DI 10.1007/978-1-59745-001-0_10 D2 10.1007/978-1-59745-001-0 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BLY72 UT WOS:000271458800011 ER PT S AU Wragg, A Boehm, M AF Wragg, Andrew Boehm, Manfred BE Duckers, HJ Nabel, EG Serruys, PW TI Cell Cycle Regulators and Vascular Proliferative Diseases SO ESSENTIALS OF RESTENOSIS: FOR THE INTERVENTIONAL CARDIOLOGIST SE Contemporary Cardiology LA English DT Article; Book Chapter ID DEPENDENT KINASE INHIBITOR; ENDOTHELIAL PROGENITOR CELLS; SMOOTH-MUSCLE-CELLS; PACLITAXEL-ELUTING STENT; RAT CAROTID-ARTERY; GROWTH-FACTOR-I; CORONARY-ARTERY; CDK INHIBITORS; BONE-MARROW; INTIMAL HYPERPLASIA C1 [Wragg, Andrew; Boehm, Manfred] NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Wragg, A (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 93 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-001-0 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2007 BP 199 EP 212 DI 10.1007/978-1-59745-001-0_12 D2 10.1007/978-1-59745-001-0 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BLY72 UT WOS:000271458800013 ER PT S AU Nabel, EG AF Nabel, Elizabeth G. BE Duckers, HJ Nabel, EG Serruys, PW TI Cell Cycle Approaches to the Treatment of In-Stent Restenosis SO ESSENTIALS OF RESTENOSIS: FOR THE INTERVENTIONAL CARDIOLOGIST SE Contemporary Cardiology LA English DT Article; Book Chapter ID DEPENDENT KINASE INHIBITOR; GENE-EXPRESSION INVIVO; DRUG-ELUTING STENTS; MICE LACKING; CORONARY-ARTERIES; VASCULAR-DISEASE; T-LYMPHOCYTES; P27(KIP1); MUSCLE; PROLIFERATION C1 NHLBI, Nabel Lab, Genome Technol Branch, NHGRI,Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Nabel Lab, Genome Technol Branch, NHGRI,Div Intramural Res,NIH, Bldg 10, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1191-7601 BN 978-1-59745-001-0 J9 CONTEMP CARDIOL JI Contemp. Cardiol. PY 2007 BP 407 EP + DI 10.1007/978-1-59745-001-0_26 D2 10.1007/978-1-59745-001-0 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BLY72 UT WOS:000271458800027 ER PT J AU Robinson, JM Trochim, WMK AF Robinson, JaMuir M. Trochim, William M. K. TI An examination of community members', researchers' and health professionals' perceptions of barriers to minority participation in medical research: An application of concept mapping SO ETHNICITY & HEALTH LA English DT Article DE minority populations; medical research; concept mapping; recruitment; clinical trials ID CANCER CLINICAL-TRIALS; AFRICAN-AMERICANS; LUNG-CANCER; REPRESENTATION; DISPARITIES; ENROLLMENT AB Objective. Some of the most promising medical treatments are currently being developed and used in clinical trials. In the US, rates of chronic disease among racial/ethnic minorities are disproportionately high. Unfortunately, the rates of minority participation in medical research are low, and the reasons are unclear. This study seeks to contribute to the body of knowledge that is currently available relating to the specific barriers to racial/ethnic minority participation in medical research through the conceptualization and measurement of these barriers. Design. Study participants included a convenience sample obtained from the National Cancer Institute's Special Populations Networks, and consisted of practitioners, researchers and community members who specialize in research related to the treatment and prevention of cancer. A structured form of concept mapping (Trochim 1989) was the methodology used in this study. The concept mapping process has three specific phases: (1) project planning-development of project focus statements and sample selection (2) idea generation and structuring and (3) analysis and interpretation. This method is analogous to a more formalized and structured focus group approach, and involved the gathering of 149 ideas and the sorting of 70 statements. Comparisons across participant demographics were conducted and are presented in the form of pattern matches. Results. The findings of this study suggest that there are two specific areas where barriers to minority participation may be addressed. The first area is the research system, specifically, the manner in which research studies are designed and implemented, including referral, recruitment and retention of racial/ethnic minorities. The data suggest that recruitment and retention will be aided by addressing patient concerns regarding the research process, and assuaging fears about clinical trials. The second area pertains to minority perceptions of the research process based on history and personal experiences. Conclusion. There appears to be a difference in the barriers to participation as defined by community members themselves, and health professionals' perceptions of these barriers. Increased inclusion of minorities in the design, management, and implementation of medical research studies would help mitigate negative perceptions of the research process, and serve to increase participation among racial/ethnic minorities. C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Off Educ & Special Initiat, NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. RP Robinson, JM (reprint author), 6116 Execut Blvd,Suite 202,MSC 8334, Rockville, MD 20852 USA. EM JaMuir.Robinson@gmail.com RI Trochim, William/A-1250-2007 OI Trochim, William/0000-0003-0369-2922 NR 36 TC 48 Z9 48 U1 1 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-7858 J9 ETHNIC HEALTH JI Ethn. Health PY 2007 VL 12 IS 5 BP 521 EP 539 DI 10.1080/13557850701616987 PG 19 WC Ethnic Studies; Public, Environmental & Occupational Health SC Ethnic Studies; Public, Environmental & Occupational Health GA 237IN UT WOS:000251367500007 PM 17978947 ER PT J AU Stoddard, JL Dent, CW Shames, L Bernstein, L AF Stoddard, Jacqueline L. Dent, Clyde W. Shames, Lisa Bernstein, Leslie TI Exercise training effects on premenstrual distress and ovarian steroid hormones SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE premenstrual syndrome; menstrual cycle; physical activity; endocrinology; ovarian hormones ID MENSTRUAL-CYCLE; PROGESTERONE CONCENTRATIONS; POSTMENOPAUSAL WOMEN; PITUITARY-OVARIAN; PHYSICAL EXERCISE; ORAL PROGESTERONE; MOOD; SYMPTOMS; METABOLITES; ESTROGEN AB Preliminary studies suggest that moderate physical activity may reduce both premenstrual distress (PD) and the ovarian steroid hormones, progesterone and estradiol, which have been implicated in PD. We attempted to replicate these findings, while exploring possible relationships between hormone levels and PD. In a cross-sectional study, 20 moderate exercisers and 34 sedentary women completed PD symptom questionnaires and collected urine samples, daily, throughout a complete menstrual cycle. PD was calculated as the difference in symptom scores reported during the average of the 4 days prior to menses and the average of the 4 days closest to mid-cycle. Urine samples taken from the last quarter of the menstrual cycle were analyzed for urinary estrone glucoronide (E1G) and pregnanediol glucoronide. In a prospective study the same measures were used with 14 sedentary women before and after a 24-week moderate exercise-training program. In the cross-sectional study, exercising women reported lower Pain symptoms, and had lower peak E1G levels than did sedentary women. The baseline PD symptoms loneliness, crying, and skin blemishes with were statistically significantly and positively correlated with pregnanediol glucoronide levels in the cross-sectional study. In the prospective study, exercise reduced the global PD symptom score, including the Water Retention and Pain scales, and reduced pregnanediol glucoronide and peak E1G levels. Moderate aerobic exercise may lessen both PD symptoms and late luteal phase ovarian hormone levels. An exercise program may benefit women with progesterone-related premenstrual affect disturbance. C1 NCI, Div Canc Control & Populat Sci, Behav Res Program, Tobacco Control Res Branch, Bethesda, MD 20892 USA. Univ So Calif, Dept Prevent Med, Alhambra, CA 91803 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Stoddard, JL (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Tobacco Control Res Branch, 6130 Execut Blvd,MSC 7337,Execut Plaza N Room 404, Bethesda, MD 20892 USA. EM stoddaja@mail.nih.gov; cdent@use.edu; lshames@amgen.com; lbern@usc.edu RI Loureiro, Nuno/I-6400-2012 OI Loureiro, Nuno/0000-0002-1166-3219 NR 39 TC 16 Z9 18 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1439-6319 J9 EUR J APPL PHYSIOL JI Eur. J. Appl. Physiol. PD JAN PY 2007 VL 99 IS 1 BP 27 EP 37 DI 10.1007/s00421-006-0313-7 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 122XF UT WOS:000243260200004 PM 17039366 ER PT J AU Messersmith, WA Rudek, MA Baker, SD Zhao, M Collins, C Colevas, AD Donehower, RC Carducci, MA Wolff, AC AF Messersmith, Wells A. Rudek, Michelle A. Baker, Sharyn D. Zhao, Ming Collins, Connie Colevas, A. Dimitrios Donehower, Ross C. Carducci, Michael A. Wolff, Antonio C. TI Phase I study of continuous weekly dosing of dimethylamino benzoylphenylurea (BPU) in patients with solid tumours SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE tubulin inhibitor; pharmacokinetics; accelerated titration introduction ID ANTITUMOR ACTIVITIES; HUMAN PLASMA; CLINICAL-PHARMACOLOGY; DERIVATIVES; DESIGNS; HO-221; VITRO; UREA AB A phase I study of dimethylamino benzoylphenylurea (BPU), a tubulin inhibitor, was performed using a weekly continuous schedule. Patients with refractory solid tumours received oral BPU once weekly without interruption at doses ranging from 5 to 320 mg using an accelerated titration design. Nineteen subjects received 54 cycles of BPU. Early pharmacokinetic findings of decreased clearance with increasing dose and plasma accumulation led to the expansion of the 320 mg dose level. Two subjects then developed late haematologic dose-limiting toxicities (DLTs) that were associated with the highest plasma exposure to BPU and metabolites. Study enrollment resumed at dose 150 mg with real-time pharmacokinetic monitoring. Seven additional subjects (6 evaluable) were treated for a median of 2 cycles (range 1.5-4) without further myelotoxicity. A long half-life and accumulation of BPU and active metabolites were observed, recommending against a continuous administration. Weekly oral BPU therapy should be further tested using an interrupted schedule. (c) 2006 Elsevier Ltd. All rights reserved. C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Messersmith, WA (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Bunting Blaustein Canc Res Bldg,CRB 1M88,1650 Orl, Baltimore, MD 21231 USA. EM wmesser1@jhmi.edu OI Wolff, Antonio/0000-0003-3734-1063 FU NCI NIH HHS [P30CA069773, U01 CA070095, U01 CA70095] NR 25 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2007 VL 43 IS 1 BP 78 EP 86 DI 10.1016/j.ejca.2006.09.006 PG 9 WC Oncology SC Oncology GA 137RZ UT WOS:000244311000019 PM 17084620 ER PT J AU Bredart, A Coens, C Aaronson, N Chie, WC Efficace, F Conroy, T Blazeby, JM Hammerlid, E Costantini, M Joly, F Schraub, S Sezer, O Arraras, JI Rodary, C Costantini, A Mehlitz, M Razavi, D Bottomley, A AF Bredart, A. Coens, C. Aaronson, N. Chie, W. -C. Efficace, F. Conroy, T. Blazeby, J. M. Hammerlid, E. Costantini, M. Joly, F. Schraub, S. Sezer, O. Arraras, J. I. Rodary, C. Costantini, A. Mehlitz, M. Razavi, D. Bottomley, A. CA EORTC Qual Lif Grp EORTC Qual Lif Un TI Determinants of patient satisfaction in oncology settings from European and Asian countries: Preliminary results based on the EORTC IN-PATSAT32 questionnaire SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE patient satisfaction; determinant; cross-cultural; oncology ID QUALITY-OF-LIFE; INPATIENT SATISFACTION; CLINICAL-TRIALS; CANCER-PATIENTS; HOSPITAL-CARE; HEALTH-STATUS; INFORMATION; PREFERENCES; INSTRUMENT; DISCLOSURE AB The aim of this study was to identify factors associated significantly with hospitalised cancer patients' satisfaction with care. Patients were recruited from four geographical/cultural groups, including five European countries and Taiwan. They rated their level of satisfaction by completing the EORTC IN-PATSAT32 questionnaire at home. Additionally, data were collected on the sociodemographic and clinical characteristics and the quality of life of the patients, as well as on institutional characteristics. Of 762 patients recruited, 647 (85%) returned a completed questionnaire. The number of nurses and doctors per bed, institution size, geo-cultural origin, ward setting, teaching/non-teaching setting, treatment toxicity, global health status, participation in clinical trials and education level were all associated significantly at the multivariate level with satisfaction with doctor and nurse interpersonal skills, information provision, availability, and/or overall satisfaction. A number of patient-, institutional- and culture-related factors are associated with the perceived quality of cancer care. Future studies, with appropriate sampling frames and stratification procedures, are needed to better understand cross-national and cross-cultural differences in cancer patient satisfaction. (c) 2006 Elsevier Ltd. All rights reserved. C1 Inst Curie, Psychooncol Unit, F-75005 Paris 05, France. Eortc Data Ctr, Brussels, Belgium. Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. Natl Taiwan Univ, Taipei 10764, Taiwan. EORTC Qual Life Unit, Brussels, Belgium. Ctr Alexis Vautrin, Nancy, France. Univ Bristol, Bristol, Avon, England. Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. Natl Canc Inst, Genoa, Italy. Ctr Francois Baclesse, F-14021 Caen, France. Ctr Paul Strauss, Strasbourg, France. Univ Hosp Charite, Berlin, Germany. Hosp Navarra, Pamplona, Spain. Inst Gustave Roussy, Villejuif, France. Univ Roma La Sapienza, St Andreas Hosp, Rome, Italy. Bruederkrankenhaus, Trier, Germany. Inst Jules Bordet, B-1000 Brussels, Belgium. RP Bredart, A (reprint author), Inst Curie, Psychooncol Unit, 26 Rue Ulm, F-75005 Paris 05, France. EM anne.bredart@curie.net RI costantini, massimo/G-1443-2012; OI costantini, massimo/0000-0002-5293-7079; Chie, Wei-Chu/0000-0001-5584-6554; Blazeby, Jane/0000-0002-3354-3330 FU NCI NIH HHS [2U10 CA11488-31, 3U10 CA11488-31, 4U10 CA11488-31, 5U10 CA11488-35] NR 24 TC 28 Z9 29 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2007 VL 43 IS 2 BP 323 EP 330 DI 10.1016/j.ejca.2006.10.016 PG 8 WC Oncology SC Oncology GA 138QQ UT WOS:000244377700025 PM 17156997 ER PT J AU Stookey, JD Burg, M Sellmeyer, DE Greenleaf, JE Arieff, A Van Hove, L Gardner, C King, JC AF Stookey, J. D. Burg, M. Sellmeyer, D. E. Greenleaf, J. E. Arieff, A. Van Hove, L. Gardner, C. King, J. C. TI A proposed method for assessing plasma hypertonicity in vivo SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE hypertonicity; sodium; hydration; MCV; hematocrit ID MEAN CORPUSCULAR VOLUME; RED-CELL VOLUME; AUTOMATED MEASUREMENT; OSMOTIC ERROR; HYPERGLYCEMIA; ANTICOAGULANT; ERYTHROCYTES; DEHYDRATION; HEMATOCRIT; INACCURACY AB Indices of plasma hypertonicity, elevated plasma concentrations of solutes that draw fluid out of cells by osmosis, are needed to pursue hypertonicity as a possible risk factor for obesity and chronic disease. This paper proposes a new index that may be more sensitive to mild hypertonicity in vivo at a point in time than traditional measures. The index compares mean corpuscular volume (MCV) estimates from diluted (in solution by automated cell counter) and nondiluted blood (calculated from manual hematocrit, MCV Hct/RBC*10(6)). A larger Auto vs Manual MCV (> 2 fl) in vitro indicates hypertonicity in vivo if the cell counter diluent is isotonic with the threshold for plasma vasopressin (PVP) release and PVP is detectable in plasma (> 0.5 pg/ml). To evaluate this principle of concept, hypertonicity was induced by 24-h fluid restriction after a 20 ml/kg water load in four healthy men (20-46 years). Unlike serum and urine indices, the MCV difference-&-PVP index detected hypertonicity in all participants. C1 Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. NHLBI, LKEM, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NASA, Ames Res Ctr, Moffett Field, CA 94035 USA. Abbott Diagnost Div, Abbott Pk, IL USA. Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. RP Stookey, JD (reprint author), Childrens Hosp Oakland, Res Inst, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA. EM jstookey@chori.org FU NCRR NIH HHS [M01 RR-00070]; NHLBI NIH HHS [5 T32 HL 07034] NR 30 TC 4 Z9 4 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD JAN PY 2007 VL 61 IS 1 BP 143 EP 146 DI 10.1038/sj.ejcn.1602481 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 116VD UT WOS:000242830700022 PM 16855542 ER PT J AU Chauhan, SC Kumar, D Bell, MC Koch, MD Verma, M AF Chauhan, S. C. Kumar, D. Bell, M. C. Koch, M. D. Verma, M. TI Molecular markers of miscellaneous primary and metastatic tumors of the uterine cervix SO EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY LA English DT Article DE uterine cervix; rare tumors; markers; metastatic ID ADENOID-BASAL CARCINOMA; CELL NEUROENDOCRINE CARCINOMA; NON-HODGKINS-LYMPHOMA; OF-THE-LITERATURE; PRIMITIVE NEUROECTODERMAL TUMOR; HUMAN-PAPILLOMAVIRUS INFECTION; FALLOPIAN-TUBE CARCINOMA; FEMALE GENITAL-TRACT; PROGESTERONE-RECEPTOR; MALIGNANT SCHWANNOMA AB Miscellaneous primary tumors of the uterine cervix are rare. Markers which can be utilized to detect these tumors are very few and in most cases, have not been clinically validated. The information provided in this article will help in developing strategies to discover novel markers and initiate translational research in this ignored area. Based on the reported studies, cytokeratin markers are common in many tumors and few of these rare cancers demonstrate human papilloma-virus (HPV) and Epstein Bar virus (EBV) infection. Due to the very low prevalence of these tumors, epidemiological studies have not been conducted and the etiology of these tumors is largely unknown. C1 NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. Univ Dist Columbia, Dept Obstet & Gynecol, Washington, DC USA. Univ Dist Columbia, Dept Biol & Environm Sci, Washington, DC USA. Univ S Dakota, Sanford Sch Med, Dept Lab Med, Vermillion, SD 57069 USA. RP Verma, M (reprint author), NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Execut Plaza N Room 5105, Rockville, MD 20852 USA. FU PHS HHS [U54] NR 67 TC 2 Z9 2 U1 0 U2 0 PU I R O G CANADA, INC PI MONTREAL PA 4900 COTE ST-LUC, APT#212, MONTREAL, QUEBEC H3W 2H3, CANADA SN 0392-2936 J9 EUR J GYNAECOL ONCOL JI Eur. J. Gynaecol. Oncol. PY 2007 VL 28 IS 1 BP 5 EP 14 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 136RF UT WOS:000244241100001 PM 17375698 ER PT J AU Reina-San-Martin, B Chen, JJ Nussenzweig, A Nussenzweig, MC AF Reina-San-Martin, Bernardo Chen, Junjie Nussenzweig, Andre Nussenzweig, Michel C. TI Enhanced intra-switch region recombination during immunoglobulin class switch recombination in 53BP(-/-) B cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE 53BP1; class switch recombination; DNA damage response ID CYTIDINE DEAMINASE AID; DOUBLE-STRAND BREAKS; DNA-DAMAGE; GENOMIC INSTABILITY; PROTEIN 53BP1; HISTONE H2AX; SOMATIC MUTATION; S-REGIONS; P53; ACTIVATION AB Immunoglobulin class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in single-stranded DNA. U:G mismatches created by AID are processed to produce lesions that recruit and activate DNA damage response proteins including Ataxia-telangiectasia mutated (ATM), histone H2AX, Nijmegen breakage syndrome 1 (Nbs1), and p53 binding protein 1 (53BP1). Among these proteins, absence of 53BP1 produces the most severe impairment of class switching. Here, we demonstrate that AID is targeted normally to switch region DNA and that intra-switch region recombination is enhanced in 53BP1(-/-) B cells. In addition, S mu-S gamma 1 switch region junctions cloned from 53BP1(-/-) cells show unusual insertions suggestive of failed class switching. Our data are consistent with a role for 53BP1 in stabilizing the synapsis of switch regions during CSR. C1 ULP, INSERM, CNRS, IGBMC,Illkirch CU, Strasbourg, France. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Dept Oncol, Rochester, MN USA. Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Immunol, New York, NY 10021 USA. RP Reina-San-Martin, B (reprint author), ULP, INSERM, CNRS, IGBMC,Illkirch CU, Strasbourg, France. EM reinab@igbmc.u-strasbg.fr RI Reina-San-Martin, Bernardo/I-9484-2016 OI Reina-San-Martin, Bernardo/0000-0003-2083-6166 NR 35 TC 68 Z9 68 U1 0 U2 1 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 JAN PY 2007 VL 37 IS 1 BP 235 EP 239 DI 10.1002/eji.200636789 PG 5 WC Immunology SC Immunology GA 127QC UT WOS:000243600400025 PM 17183606 ER PT J AU Chmelik, J Rehulka, P Kovacik, V Patoprsty, V Kovac, P AF Chmelik, Josef Rehulka, Pavel Kovacik, Vladimir Paetoprsty, Vladimir Kovac, Pavol TI Negative matrix-assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry fragmentation of synthetic analogs of the O-specific polysaccharide of Vibrio cholerae O : 1 in the presence of anionic dopants SO EUROPEAN JOURNAL OF MASS SPECTROMETRY LA English DT Article DE matrix-assisted laser desorption/ionization time-of-fligh/time-of-flight; MALDI-ToF/ToF negative tandem mass spectra; anion dopants; oligosaccharides from lipopolysaccharide of Vibrio cholerae O : 1; fragmentation ID METHYL ALPHA-GLYCOSIDES; SEROTYPE-OGAWA; POSITIVE-ION; ELECTROSPRAY; IONIZATION; INABA; ANTIGEN; LIPOPOLYSACCHARIDE; OLIGOSACCHARIDES; TRISACCHARIDE AB Oligosaccharides (tri- to hexamers) that represent terminal epitopes of O-antigens of Vibrio cholerae O:1, serotypes Ogawa and Inaba, have been studied by negative matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-ToF/ToF MS). The [M-H+](-) ions are formed after expulsion of a proton from molecules studied under MALDI/MS analysis conditions in the negative mode. Several ammonium salts (chloride, nitrate, hydrogencarbonate and hydrogensulfate) were used as additives to increase the formation of negative ions from saccharides. The most efficient was the addition of ammonium hydrogencarbonate, which increased the number of [M-H+](-) ions more than six times. Between three fragmentation pathways,the new conjugated transfer of electrons within the second downstream unit of oligosaccharides was discovered. Production of these ions, which has not been observed in any other kinds of measurement, distinguishes substances belonging to Ogawa and Inaba serotypes. The negative MALDI-ToF/ToF mass spectra are simpler and, at the same time, more informative, as compared with positive and negative electrospray ionization ion trap as well as with positive MALDI-ToF/ToF analysis. C1 [Kovacik, Vladimir; Paetoprsty, Vladimir] Slovak Acad Sci, Inst Chem, Bratislava 84538, Slovakia. [Chmelik, Josef; Rehulka, Pavel] Acad Sci Czech Republic, Inst Analyt Chem, CS-61142 Brno, Czech Republic. [Kovac, Pavol] NIDDK, NIH, Bethesda, MD 20892 USA. RP Kovacik, V (reprint author), Slovak Acad Sci, Inst Chem, Dubravska Cesta 9, Bratislava 84538, Slovakia. EM chemvkov@savba.sk NR 27 TC 2 Z9 2 U1 1 U2 3 PU IM PUBLICATIONS PI W SUSSEX PA 6 CHARLTON MILL, CHARLTON, CHICHESTER,, W SUSSEX PO18 0HY, ENGLAND SN 1469-0667 J9 EUR J MASS SPECTROM JI Eur. J. Mass Spectrom. PY 2007 VL 13 IS 5 BP 347 EP 353 DI 10.1255/ejms.891 PG 7 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 264FJ UT WOS:000253271700005 PM 18192728 ER PT J AU Xiromerisiou, G Hadjigeorgiou, GM Gourbali, V Johnson, J Papakonstantinou, I Papadimitriou, A Singleton, AB AF Xiromerisiou, G. Hadjigeorgiou, G. M. Gourbali, V. Johnson, J. Papakonstantinou, I. Papadimitriou, A. Singleton, A. B. TI Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variants SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE alpha-synuclein gene; leucine-rich repeat kinase 2 gene; mutation; Parkinson's disease ID ALPHA-SYNUCLEIN GENE; FAMILIES; KINDREDS AB Mutations in SNCA and LRRK2 genes, encoding alpha-synuclein and leucine-rich repeat kinase 2, respectively, cause autosomal dominant Parkinson's disease (AdPD). The LRRK2 G2019S (c.6055G > A) and R1441G (c.4321C > G) mutations have also been identified in sporadic PD (sPD). We studied 55 unrelated patients with AdPD, 235 patients with sPD, and 235 healthy age- and gender-matched controls all of Greek origin. Patients with AdPD were screened for SNCA and LRRK2 mutations by direct sequencing. SNCA gene dosage analysis was also performed for AdPD using quantitative duplex polymerase chain reaction of genomic DNA. In addition, we investigated the frequency of the LRRK2 G2019S mutation in sPD. We found no missense mutations or multiplications in the SNCA gene. Here we report two novel variants, A211V (c.632C > T) and K544E (c.1630A > G) in LRRK2 gene in two patients with AdPD that was not present in controls. We identified only one patient with sPD (1/235; 0.4%) carrying the G2019S mutation. LRRK2 mutations are present in AdPD and sPD patients of Greek origin. C1 Univ Thessaly, Sch Med, Dept Neurol, Neurogenet Unit, Larisa 41222, Greece. NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. Gen Hosp Trikala, Dept Neurol, Trikala, Greece. RP Hadjigeorgiou, GM (reprint author), Univ Thessaly, Sch Med, Dept Neurol, Neurogenet Unit, Papakyriazi 22 St, Larisa 41222, Greece. EM gmhadji@med.uth.gr RI Singleton, Andrew/C-3010-2009; Johnson, Janel/A-7136-2010 NR 22 TC 31 Z9 31 U1 2 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD JAN PY 2007 VL 14 IS 1 BP 7 EP 11 DI 10.1111/j.1468-1331.2006.01551.x PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 136GX UT WOS:000244211700002 PM 17222106 ER PT J AU Yamaguchi, T Sheen, W Morales, M AF Yamaguchi, Tsuyoshi Sheen, Whitney Morales, Marisela TI Glutamatergic neurons are present in the rat ventral tegmental area SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; midbrain; reward; Sprague-Dawley rat; substantia nigra; VGluT2 ID MIDBRAIN DOPAMINE NEURONS; INORGANIC-PHOSPHATE TRANSPORTER; GABA-CONTAINING NEURONS; VESICULAR GLUTAMATE; NUCLEUS-ACCUMBENS; INTERFASCICULAR NUCLEUS; SUBSTANTIA NIGRA; FRONTAL-CORTEX; IN-VITRO; IDENTIFICATION AB The ventral tegmental area (VTA) is thought to play an important role in reward function. Two populations of neurons, containing either dopamine (DA) or gamma-amino butyric acid (GABA), have been extensively characterized in this area. However, recent electrophysiological studies are consistent with the notion that neurons that utilize neurotransmitters other than DA or GABA are likely to be present in the VTA. Given the pronounced phenotypic diversity of neurons in this region, we have proposed that additional cell types, such as those that express the neurotransmitter glutamate may also be present in this area. Thus, by using in situ hybridization histochemistry we investigated whether transcripts encoded by genes for the two vesicular glutamate transporters, VGluT1 or VGluT2, were expressed in the VTA. We found that VGluT2 mRNA but not VGluT1 mRNA is expressed in the VTA. Neurons expressing VGluT2 mRNA were differentially distributed throughout the rostro-caudal and medio-lateral aspects of the VTA, with the highest concentration detected in rostro-medial areas. Phenotypic characterization with double in situ hybridization of these neurons indicated that they rarely co-expressed mRNAs for tyrosine hydroxylase (TH, marker for DAergic neurons) or glutamic acid decarboxylase (GAD, marker for GABAergic neurons). Based on the results described here, we concluded that the VTA contains glutamatergic neurons that in their vast majority are clearly non-DAergic and non-GABAergic. C1 Natl Inst Drug Abuse, Baltimore, MD 21224 USA. RP Morales, M (reprint author), Natl Inst Drug Abuse, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mmorales@intra.nida.nih.gov OI YAMAGUCHI, TSUYOSHI/0000-0002-0058-9244 FU Intramural NIH HHS NR 50 TC 168 Z9 170 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2007 VL 25 IS 1 BP 106 EP 118 DI 10.1111/j.1460-9568.2006.05263.x PG 13 WC Neurosciences SC Neurosciences & Neurology GA 128TQ UT WOS:000243682100011 PM 17241272 ER PT J AU Eyman, M Cefaliello, C Ferrara, E De Stefano, R Lavina, ZS Crispino, M Squillace, A van Minnen, J Kaplan, BB Giuditta, A AF Eyman, Maria Cefaliello, Carolina Ferrara, Eugenia De Stefano, Rosanna Lavina, Zeno Scotto Crispino, Marianna Squillace, Angela van Minnen, Jan Kaplan, Barry B. Giuditta, Antonio TI Local synthesis of axonal and presynaptic RNA in squid model systems SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE gene expression; giant axon; glial cells; nerve endings; RNA synthesis; synaptosomes ID PROTEIN TRANSFER HYPOTHESIS; MAUTHNER NERVE FIBRE; GIANT-AXON; GROWTH CONES; AXOPLASMIC RNA; MESSENGER-RNA; SYNAPTOSOMAL FRACTION; ACTIVE POLYSOMES; BASE COMPOSITION; RIBOSOMAL-RNA AB The presence of active systems of protein synthesis in axons and nerve endings raises the question of the cellular origin of the corresponding RNAs. Our present experiments demonstrate that, besides a possible derivation from neuronal cell bodies, axoplasmic RNAs originate in periaxonal glial cells and presynaptic RNAs derive from nearby cells, presumably glial cells. Indeed, in perfused squid giant axons, delivery of newly synthesized RNA to the axon perfusate is strongly stimulated by axonal depolarization or agonists of glial glutamate and acetylcholine receptors. Likewise, incubation of squid optic lobe slices with [H-3]uridine leads to a marked accumulation of [H-3]RNA in the large synaptosomes derived from the nerve terminals of retinal photoreceptor neurons. As the cell bodies of these neurons lie outside the optic lobe, the data demonstrate that presynaptic RNA is locally synthesized, presumably by perisynaptic glial cells. Overall, our results support the view that axons and presynaptic regions are endowed with local systems of gene expression which may prove essential for the maintenance and plasticity of these extrasomatic neuronal domains. C1 Univ Naples Federico II, Dept Biol Sci, Naples, Italy. Free Univ Amsterdam, Inst Neurosci, Dept Mol & Cellular Neurbiol, NL-1081 HV Amsterdam, Netherlands. NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Giuditta, A (reprint author), Univ Naples Federico II, Dept Biol Sci, Naples, Italy. EM giuditta@unina.it FU NIGMS NIH HHS [GM39600]; NINDS NIH HHS [NS30715] NR 69 TC 35 Z9 36 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2007 VL 25 IS 2 BP 341 EP 350 DI 10.1111/j.1460-9568.2007.05304.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 144FX UT WOS:000244783000002 PM 17284174 ER PT J AU Blasi, G Goldberg, TE Elvevag, B Rasetti, R Bertolino, A Cohen, J Alce, G Zoltick, B Weinberger, DR Mattay, VS AF Blasi, Giuseppe Goldberg, Terry E. Elvevag, Brita Rasetti, Roberta Bertolino, Alessandro Cohen, Jessica Alce, Guilna Zoltick, Brad Weinberger, Daniel R. Mattay, Venkata S. TI Differentiating allocation of resources and conflict detection within attentional control processing SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE cingulate cortex; dorsolateral prefrontal cortex; fMRI; parietal cortex; variable attentional control task ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; PREFRONTAL CORTEX; RESPONSE COMPETITION; FUNCTIONAL MRI; SELECTIVE ATTENTION; COGNITIVE CONTROL; GLOBAL FEATURES; WORKING-MEMORY; BRAIN AB Increasing demands for conflict detection and for allocation of attentional resources increase the need for attentional control. While prior evidence suggests that different cortical regions are preferentially engaged by these two attentional processes, the effect of increasing demand for conflict detection and/or allocation of attentional resources has been relatively unexplored. We designed a novel task (the 'variable attentional control'-VAC-task) that varies the demand for attentional control by increasing conflict detection and allocation of attentional resources within the same stimuli. We studied 34 subjects who underwent event-related functional magnetic resonance imaging while performing the VAC task. Increasing demand for attentional control, as reflected by longer reaction time and reduced accuracy, was associated with greater activation in the dorsolateral prefrontal cortex, parietal cortex and dorsal cingulate. Furthermore, an increase in conflict detection was associated with greater dorsal cingulate activity, whereas an increase in demand for allocation of attentional resources implied greater activation in the dorsolateral prefrontal and parietal cortices. In essence, in addition to allowing the exploration of the overall effects of increasing demand for attentional control, our novel task also allowed parsing of the neural components of attentional control into those related to allocation of attentional resources and those related to conflict detection. C1 NIMH, CBDB, GCAP, NIH, Bethesda, MD 20892 USA. Univ Bari, Dept Neurol & Psychiat Sci, Psychiat Neurosci Grp, I-70121 Bari, Italy. RP Mattay, VS (reprint author), NIMH, CBDB, GCAP, NIH, Bethesda, MD 20892 USA. EM vsm@mail.nih.gov NR 46 TC 22 Z9 22 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2007 VL 25 IS 2 BP 594 EP 602 DI 10.1111/j.1460-9568.2007.05283.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 144FX UT WOS:000244783000030 PM 17284202 ER PT J AU Dunn, EF Moy, VN Angerer, LM Angerer, RC Morris, RL Peterson, KJ AF Dunn, Ewan F. Moy, Vanessa N. Angerer, Lynne M. Angerer, Robert C. Morris, Robert L. Peterson, Kevin J. TI Molecular paleoecology: using gene regulatory analysis to address the origins of complex life cycles in the late Precambrian SO EVOLUTION & DEVELOPMENT LA English DT Review ID SEA-URCHIN EMBRYO; MARINE-INVERTEBRATE LARVAE; MOLLUSK PATELLA-VULGATA; CENTRAL-NERVOUS-SYSTEM; IN-SITU HYBRIDIZATION; APICAL SENSORY ORGAN; ANIMAL-VEGETAL AXIS; NK-2 HOMEOBOX GENE; NEMATOSTELLA-VECTENSIS; CILIARY BANDS AB Molecular paleoecology is the application of molecular data to test hypotheses made by paleoecological scenarios. Here, we use gene regulatory analysis to test between two competing paleoecological scenarios put forth to explain the evolution of complex life cycles. The first posits that early bilaterians were holobenthic, and the evolution of macrophagous grazing drove the exploitation of the pelagos by metazoan eggs and embryos, and eventually larvae. The alternative hypothesis predicts that early bilaterians were holopelagic, and new adult stages were added on when these holopelagic forms began to feed on the benthos. The former hypothesis predicts that the larvae of protostomes and deuterostomes are not homologous, with the implication that larval-specific structures, including the apical organ, are the products of convergent evolution, whereas the latter hypothesis predicts homology of larvae, specifically homology of the apical organ. We show that in the sea urchin, Strongylocentrotus purpuratus, the transcription factors NK2.1 and HNF6 are necessary for the correct spatial expression profiles of five different cilia genes. All of these genes are expressed exclusively in the apical plate after the mesenchyme-blastula stage in cells that also express NK2.1 and HNF6. In addition, abrogation of SpNK2.1 results in embryos that lack the apical tuft. However, in the red abalone, Haliotis rufescens, NK2.1 and HNF6 are not expressed in any cells that also express these same five cilia genes. Nonetheless, like the sea urchin, the gastropod expresses both NK2.1 and FoxA around the stomodeum and foregut, and FoxA around the proctodeum. As we detected no similarity in the development of the apical tuft between the sea urchin and the abalone, these molecular data are consistent with the hypothesis that the evolution of mobile, macrophagous metazoans drove the evolution of complex life cycles multiple times independently in the late Precambrian. C1 Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA. Wheaton Coll, Dept Biol, Norton, MA 02766 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Peterson, KJ (reprint author), Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA. EM kevin.peterson@dartmouth.edu RI Peterson, Kevin/A-2188-2009 FU Intramural NIH HHS; NIGMS NIH HHS [GM25553] NR 118 TC 35 Z9 35 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-541X EI 1525-142X J9 EVOL DEV JI Evol. Dev. PD JAN-FEB PY 2007 VL 9 IS 1 BP 10 EP 24 PG 15 WC Evolutionary Biology; Developmental Biology; Genetics & Heredity SC Evolutionary Biology; Developmental Biology; Genetics & Heredity GA 124WV UT WOS:000243403600002 PM 17227363 ER PT J AU Clayton, NP Yoshizawa, K Kissling, GE Burka, LT Chan, PC Nyska, A AF Clayton, Natasha P. Yoshizawa, Katsuhiko Kissling, Grace E. Burka, Leo T. Chan, Po-Chuen Nyska, Abraham TI Immunohistochemical analysis of expressions of hepatic cytochrome P450 in F344 rats following oral treatment with kava extract SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE kava; Piper methysticum; herb; hepatocellular hypertrophy; cytochrome P450; F344 rat ID ZERO-DOSE CONTROL; HERB-DRUG INTERACTIONS; IN-VIVO; KAVALACTONES; METABOLISM; TOXICOLOGY; INDUCTION; HEPATOTOXICITY; POLYMORPHISMS; XENOBIOTICS AB Kava (Piper methysticum), used for relaxation and pain relief, has been one of the leading dietary supplements and several reports linking hepatic functional disturbances and liver failure to kava have resulted in a ban on sales in Europe and Canada and the issuance of warnings by the US FDA. The National Toxicology Program conducted 14-week rat studies to characterize the toxicology of kava exposure in Fischer 344 rats [National Toxicity Program. 90 day gavage toxicity studies of KAVA KAVA EXTRACT in Fischer rats and B6C3F1 mice. Research Triangle Park, NC 2005a; National Toxicity Program. Testing status of agents at NTP (KAVA KAVA EXTRACT M990058). Research Triangle Park, NC; 2005b. (http://ntp.niehs.nih.gov/ index.cfm?objectid=071516E-C6E1-7AAA-C9OC751E23D14C1B)]. Groups of 10 male and 10 female rats were administered kava extract by gavage at 0, 0. 125, 0.25, 0.5, 1.0, and 2.0 g/kg/day. Increased gamma-glutamyl-transpeptidase (GGT) activities were observed in the 2.0g/kg males and 1.0 and 2.0g/kg females, as well as increased serum cholesterol levels in males and females at 0.5g/kg and higher. Increases in incidence and severity of hepatocellular hypertrophy (HP) were noted in males at 1.0g/kg and females at 0.5g/kg and higher, as well as increased liver weights. Immunohistochemical analyses of the expression of cytochrome-P450 (CYP) enzymes in liver of the control and 1.0- and 2.0-g/kg-treated groups indicated decreased expression of CYP2D1 (human CYP2D6 homolog) in 2.0g/kg females and increased expression of CYP1A2, 2B1, and 3A1 in 1.0 and 2.0g/kg groups of both sexes. The no observed adverse effect levels were decided as 0.25g/kg in both genders, based on neurotoxic effects, increases in GGT, cholesterol, liver weight, and HP and decreases in body weight. Kava-induced hepatic functional changes in the F344 rat might be relevant to human clinical cases of hepatotoxicity following exposure. (c) 2006 Elsevier GmbH. All rights reserved. C1 Haharuv, Timrat, Israel. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Astellas Pharma Inc, Toxicol Pathol Drug Safety Res Labs, Yodogawa, Osaka 5328514, Japan. Kansai Med Univ, Osaka 5708506, Japan. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), Haharuv, Timrat, Israel. EM anyska@bezeqint.net FU Intramural NIH HHS [Z99 ES999999] NR 60 TC 32 Z9 33 U1 1 U2 3 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD JAN PY 2007 VL 58 IS 4 BP 223 EP 236 DI 10.1016/j.etp.2006.08.002 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA 127LW UT WOS:000243588700002 PM 17059882 ER PT J AU Deshpande, N Patla, AE AF Deshpande, Nandini Patla, Aftab E. TI Visual-vestibular interaction during goal directed locomotion: effects of aging and blurring vision SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE vestibular system; vision; sensory integration; locomotion; aging ID HUMAN WALKING; OPTIC FLOW; GALVANIC STIMULATION; POSTURAL RESPONSES; BALANCE CONTROL; OLDER-ADULTS; HUMAN GAIT; INFORMATION; SENSITIVITY; INTEGRATION AB Normal vision overrides perturbed vestibular information for the optimization of performance during goal directed locomotion, suggesting down-regulation of vestibular gain. However, it is not known if the responses to vestibular perturbation are accentuated when vision is impaired. Furthermore, both visual and vestibular systems deteriorate with age. It is not clear, however, how age-related decline in these sensory systems influences visual-vestibular interaction. Therefore, the dual purpose of the present study was to investigate the effects of aging and blurring vision, that simulated the consequences of cataracts, on visual-vestibular interaction. Young and healthy elderly walked to a target located straight ahead with either normal or blurring vision. On randomly selected trials vestibular system perturbation was achieved by applying transmastoidal galvanic vestibular stimulation (GVS). Two different galvanic stimulation intensities were used to provide insight into scaling effect of vestibular perturbation on locomotor performance and how age and vision influences this scaling effect. Maximum path deviation, frontal trunk tilt and postural coordination in the mediolateral direction were evaluated. The magnitude of the path deviation and the trunk tilt response were scaled to the magnitude of the vestibular perturbation in older adults independent of the visual condition. Older participants demonstrated increased coupling of the head and trunk segments irrespective of visual and vestibular perturbations. The results suggest that when visual information was available, the vestibular input reweighting was less effective in older individuals, as shown by the scaled responses to the GVS intensities and the inability to converge efficiently towards the target. C1 Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD 21225 USA. Univ Waterloo, Dept Kinesiol, Gait & Posture Lab, Waterloo, ON N2L 3G1, Canada. RP Deshpande, N (reprint author), Harbor Hosp, NIA, Clin Res Branch, 3001 Hanover St S, Baltimore, MD 21225 USA. EM deshpanden@mail.nih.gov NR 37 TC 24 Z9 26 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2007 VL 176 IS 1 BP 43 EP 53 DI 10.1007/s00221-006-0593-5 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 144HQ UT WOS:000244787500005 PM 16847610 ER PT J AU Kobayashi, S Kawagoe, R Takikawa, Y Koizumi, M Sakagami, M Hikosaka, O AF Kobayashi, Shunsuke Kawagoe, Reiko Takikawa, Yoriko Koizumi, Masashi Sakagami, Masamichi Hikosaka, Okihide TI Functional differences between macaque prefrontal cortex and caudate nucleus during eye movements with and without reward SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE basal ganglia; primate; single-neuron recording; working memory ID PRIMATE BASAL GANGLIA; FRONTAL-LOBE DAMAGE; RHESUS-MONKEY; PARKINSONS-DISEASE; INTERNAL GENERATION; ANTERIOR STRIATUM; EXPECTATION; NEURONS; DOPAMINE; PROJECTIONS AB The prefrontal cortex and the basal ganglia form mutually connected networks and are thought to play essential roles together in guiding goal-directed behaviors. Yet, these structures seem to have independent pathways to motor outputs as well, suggesting differential contributions to goal-directed behaviors. We hypothesized that the prefrontal cortex guides actions to a direction required by external demands and the basal ganglia guide actions to an internally motivated direction. To test this hypothesis, we used a task in which monkeys were required to make a memory-guided saccade to a direction indicated by a visual cue while only one direction was associated with reward. We observed a functional dissociation between the lateral prefrontal cortex (LPFC), which commonly represented the cue direction, and the caudate nucleus (CD), which commonly represented the reward-associated direction. Furthermore, cue-directed and reward-directed signals were integrated differently in the two areas; when the cue direction and the reward direction were opposite, LPFC neurons maintained tuning to the cue direction, whereas CD neurons lost the tuning. Different types of spatial tuning in the two brain areas may contribute to different types of goal-directed behavior. C1 Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England. Tamagawa Univ, Res Inst, Brain Sci Res Ctr, Tokyo 1948610, Japan. Juntendo Univ, Sch Med, Dept Physiol, Bunkyo Ku, Tokyo 1138421, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Med, Dept Neurol, Div Neurosci,Bunkyo Ku, Tokyo 1138654, Japan. RP Kobayashi, S (reprint author), Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3DY, England. EM skoba-tky@umin.ac.jp RI Kobayashi, Shunsuke/C-2551-2008 NR 43 TC 33 Z9 34 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2007 VL 176 IS 2 BP 341 EP 355 DI 10.1007/s00221-006-0622-4 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 109UT UT WOS:000242335100014 PM 16902776 ER PT J AU Lee, HS Tomarev, SI AF Lee, Hee-Sheung Tomarev, Stanislav I. TI Optimedin induces expression of N-cadherin and stimulates aggregation of NGF-stimulated PC12 cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE olfactomedin; optimedin; PC12; N-cadherin; beta-catenin; siRNA ID OPEN-ANGLE GLAUCOMA; FACTOR-INDUCED DIFFERENTIATION; PROTEIN-COUPLED RECEPTORS; ALPHA-LATROTOXIN; LIPID RAFTS; OLFACTOMEDIN-DOMAIN; GENE-EXPRESSION; IDENTIFICATION; GLYCOPROTEIN; MYOCILIN AB Optimedin, also known as olfactomedin 3, belongs to a family of olfactomedin domain-containing proteins. It is expressed in neural tissues and Pax6 is involved in the regulation of its promoter. To study possible effects of optimedin on the differentiation of neural cells, we produced stably transfected PC12 cell lines expressing optimedin under a tetracycline-inducible promoter. Cells expressing high levels of optimedin showed higher growth rates and stronger adhesion to the collagen extracellular matrix as compared with control PC12 cells. After stimulation with nerve growth factor (NGF), optimedin-expressing cells demonstrated elevated levels of N-cadherin, beta-catenin, alpha-catenin and occludin as compared with stimulated, control PC12 cells. Expression of optimedin induced Ca2+-dependent aggregation of NGF-stimulated PC12 cells and this aggregation was blocked by the expression of N-cadherin siRNA. Expression of optimedin also changed the organization of the actin cytoskeleton. and inhibited neurite outgrowth in NGF-stimulated PC12 cells. We suggest that expression of optimedin stimulates the formation of adherent and tight junctions on the cell surface and this may play an important role in the differentiation of the brain and retina through the modulation of cytoskeleton. organization, cell-cell adhesion and migration. C1 NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tomarev, SI (reprint author), NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH, Bldg 7,Room 103,MSC 0704, Bethesda, MD 20892 USA. EM tomarevs@nei.nih.gov FU NEI NIH HHS [Z01 EY000311-10, Z01 EY000318-08] NR 46 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 1 PY 2007 VL 313 IS 1 BP 98 EP 108 DI 10.1016/j.yexcr.2006.09.021 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 123NS UT WOS:000243303200009 PM 17054946 ER PT J AU Estey, T Piatigorsky, J Lassen, N Vasiliou, V AF Estey, Tia Piatigorsky, Joram Lassen, Natalie Vasiliou, Vasilis TI ALDH3A1: a corneal crystallin with diverse functions SO EXPERIMENTAL EYE RESEARCH LA English DT Review DE ALDH3A1; corneal crystallin; oxidative stress; lipid peroxidation; cell growth ID NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE; LENS EPITHELIAL-CELLS; MAJOR SOLUBLE-PROTEIN; ALDEHYDE DEHYDROGENASE; ULTRAVIOLET-LIGHT; LIPID-PEROXIDATION; GLUTATHIONE-PEROXIDASE; OXIDATIVE STRESS; IMMUNOHISTOCHEMICAL LOCALIZATION; SUPEROXIDE-DISMUTASE AB Aldehyde dehydrogenase 3A1 (ALDH3A1) comprises a surprisingly high proportion (5-50% depending on species) of the water-soluble protein of the mammalian cornea, but is present little if at all in the cornea of other species. Mounting experimental evidence demonstrates that this abundant corneal protein plays an important role in the protection of ocular structures against oxidative damage. Corneal ALDH3A1 appears to protect against UV-induced oxidative stress through a variety of biological functions Such as the metabolism of toxic aldehydes produced during the peroxidation of cellular lipids, the generation of the antioxidant NADPH, the direct absorption of UV-light, the scavenging of reactive oxygen species (ROS), and the possession of chaperone-like activity. With analogies to the abundant, multifunctional, and taxon-specific lens crystallins, mammalian ALDH3A1 has been considered a corneal crystallin, Suggesting that it may contribute to the optical properties of the cornea as well. Recent studies have also revealed a novel role for ALDH3A1 in the regulation of the cell cycle. ALDH3A1-transfected HCE cells have increased population-doubling time, decreased plating efficiency, and reduced DNA synthesis, most likely due to a profound inhibition of cyclins and cyclin-dependent kinases. We have proposed that the ALDH3A1-induced reduction in cell growth may contribute to protection against oxidative stress by extending time for DNA and cell repair. Taken together, the multiple roles of ALDH3A1 against oxidative stress in addition to its contributions to the optical properties of the cornea are consistent with the idea that this specialized protein performs diverse biological functions as do the lens crystallins. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Sch Pharm,Ctr Pharmaceut Biotechnol, Mol Toxicol & Environm Hlth Sci Program,Dept Phar, Denver, CO 80262 USA. NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Mol Toxicol & Environm Hlth Sci Program, Denver, CO 80262 USA. RP Vasiliou, V (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Pharm,Ctr Pharmaceut Biotechnol, Mol Toxicol & Environm Hlth Sci Program,Dept Phar, 4200 E 9th Ave, Denver, CO 80262 USA. EM vasilis.vasiliou@uchsc.edu FU NEI NIH HHS [R01 EY11490] NR 142 TC 83 Z9 86 U1 0 U2 7 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 JAN PY 2007 VL 84 IS 1 BP 3 EP 12 DI 10.1016/j.exer.2006.04.010 PG 10 WC Ophthalmology SC Ophthalmology GA 123JP UT WOS:000243292500002 PM 16797007 ER PT J AU Leandri, M Saturno, M Cilli, M Bisaglia, M Lunardi, G AF Leandri, Massimo Saturno, Moreno Cilli, Michele Bisaglia, Michela Lunardi, Gianlulgi TI Compound action potential of sensory tail nerves in the rat SO EXPERIMENTAL NEUROLOGY LA English DT Article DE conduction velocity; rat tail; sensory; motor; compound action potential ID PERIPHERAL NERVOUS-SYSTEM; CONDUCTION AB Assessment of the conduction velocity of motor fibers of the rat tail nerves has been used by some authors in the past, but very little is known about the sensory fibers. In 10 adult rats, weighing between 320 and 380 g, responses from the nerves and muscles of the tail have been recorded after stimulation at its root and tip. It was found that stimulation of the tip involved mainly sensory fibers, of which two main groups could be identified. One faster group, conducting within the range of 38-27 m/s, and one slower group with range 14-7 m/s. The bipolar recording configuration was found to be optimal for sensory recording. Stimulation of the tail root evoked a motor response, which was preceded by a very small neurographic activity, due to the fastest sensory fibers conducting antidromically. The conduction velocity of motor fibers was calculated to be approximately 19 m/s. Distance traveled by the volley can be assessed with excellent precision on the tail nerves; hence the calculated conduction velocities are highly reliable and reproducible. We propose that the tail nerves may be a useful tool for evaluation of conduction velocity of A beta and A delta afferents. As the technique is just minimally invasive, the test can be repeated a number of times in animals under chronic experimental conditions. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Genoa, Interuniv Ctr Pain Neurophysiol, I-16146 Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, I-16146 Genoa, Italy. Natl Canc Inst, Ctr Pain Relief, Genoa, Italy. Natl Canc Inst, Anim Med Facil, Genoa, Italy. RP Leandri, M (reprint author), Univ Genoa, Interuniv Ctr Pain Neurophysiol, Via Dodecaneso 35, I-16146 Genoa, Italy. EM massimo.leandri@unige.it OI Leandri, Massimo/0000-0002-5197-7431 NR 11 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2007 VL 203 IS 1 BP 148 EP 157 DI 10.1016/j.expneurol.2006.08.001 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 123NU UT WOS:000243303400017 PM 16962099 ER PT J AU Tsujimoto, S Kuwajima, M Sawaguchi, T AF Tsujimoto, Satoshi Kuwajima, Mariko Sawaguchi, Toshiyuki TI Developmental fractionation of working memory and response inhibition during childhood SO EXPERIMENTAL PSYCHOLOGY LA English DT Article DE executive function; prefrontal cortex; children; preschool-age; school-age ID COGNITIVE-DEVELOPMENT; CORTICAL ACTIVATION; PREFRONTAL CORTEX; CHILDREN; HUMANS; TASK; ADOLESCENCE; PERFORMANCE; ATTENTION; MONKEYS AB The lateral prefrontal cortex (LPFC) plays a major role in both working memory (WM) and response inhibition (RI), which are fundamental for various cognitive abilities. We explored the relationship between these LPFC functions during childhood development by examining the performance of two groups of children in visuospatial and auditory WM tasks and a go/no-go RI task. In the younger children (59 5- and 6-year-olds), performance on the visuospatial WM task correlated significantly with that in the auditory WM task. Furthermore, accuracy in these tasks correlated significantly with performance on the RI task, particularly in the no-go trials. In contrast, there were no significant correlations among those tasks in older children (92 8- and 9-year-olds). These results suggest that functional neural systems for visuospatial WM, auditory WM, and RI, especially those in the LPFC, become fractionated during childhood, thereby enabling more efficient processing of these critical cognitive functions. C1 Hokkaido Univ, Grad Sch Med, Lab Cognit Neurobiol, Sapporo, Hokkaido, Japan. RP Tsujimoto, S (reprint author), NIMH, Lab Syst Neurosci, Bldg 49,Room BIEE17,49 Convent Dr,MSC 4401, Bethesda, MD 20892 USA. EM tsujimotos@mail.nih.gov RI Tsujimoto, Satoshi/B-8223-2011 NR 38 TC 26 Z9 29 U1 3 U2 9 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 1618-3169 J9 EXP PSYCHOL JI Exp. Psychol. PY 2007 VL 54 IS 1 BP 30 EP 37 DI 10.1027/1618-3169.54.1.30 PG 8 WC Psychology, Experimental SC Psychology GA 134VF UT WOS:000244111700004 PM 17341012 ER PT J AU Le Foll, B Goldberg, SR Sokoloff, P AF Le Foll, Bernard Goldberg, Steven R. Sokoloff, Pierre TI Dopamine D-3 receptor ligands for the treatment of tobacco dependence SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE BP-897; bupropion; conditioning dependence; dopamine D-3; nicotine; relapse; rimonabant; SB-27701 1A; tobacco; varenicline ID DOPAMINE D-3 RECEPTOR; SUSTAINED-RELEASE BUPROPION; CONDITIONED PLACE PREFERENCES; SMOKING-CESSATION GUIDELINES; CONTINUOUS NICOTINE INFUSION; RANDOMIZED CONTROLLED-TRIAL; NEUROTROPHIC FACTOR; DISCRIMINATIVE-STIMULUS; SEEKING BEHAVIOR; COCAINE-SEEKING AB This review considers the potential use of the dopamine D-3 receptor (DRD3) as a novel therapeutic target for the treatment of tobacco dependence. Among the 5 dopamine receptors identified, the DRD3 is located in the nucleus accumbens, ventral tegmental area and amygdala: 3 brain structures that are implicated in the motivational control of drug-seeking behaviour and drug-conditioning processes. Although it has been proposed that modulating dopamine transmission would be effective in the treatment of drug dependence, no validation has been provided in humans so far. Several highly selective DRD3 ligands have recently been evaluated in preclinical models of drug dependence. These ligands act as DRD3 antagonists in vivo and are able to decrease the motivation to take various drugs of abuse and reduce the influence of associated drug-conditioned behaviour. Of note is that these effects have been found with nicotine-seeking behaviour and nicotine relapse in rodents, suggesting a potential use of these ligands for the treatment of tobacco smokers. In contrast to nicotine replacement therapy, varenicline and bupropion (which are currently used for the treatment of smokers), DRD3 antagonists do not seem to produce nicotine-like effects in experimental animals and, therefore, may not substitute for nicotine or alleviate nicotine withdrawal symptoms in human smokers. This behavioural profile, which was also reported recently with cannabinoid CB, receptor antagonists, may result from effects on specific brain pathways that express DRD3 receptors and are involved in relapse and conditioning processes. These preclinical studies suggest that the clinical evaluation of DRD3 ligands should be performed with clinical trials designed specifically to evaluate the relapse phenomena. C1 Univ Toronto, Ctr Addict & Mental Hlth, Dept Family & Community Med Psychiat & Pharmacol, Translat Addict Res Lab, Toronto, ON M5S 2S1, Canada. Natl Inst Drug Abuse, Behav Neurosci Branch, Preclin Pharmacol Sect, Bethesda, MD USA. Ctr Rech Pierre Fabre, Dept Neurol & Psychiat, F-81106 Castres, France. RP Sokoloff, P (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Dept Family & Community Med Psychiat & Pharmacol, Translat Addict Res Lab, 33 Russell St, Toronto, ON M5S 2S1, Canada. EM pierre.sokoloff@pierre-fabre.com RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 116 TC 25 Z9 25 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JAN PY 2007 VL 16 IS 1 BP 45 EP 57 DI 10.1517/13543784.16.1.45 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 117WO UT WOS:000242904200005 PM 17155853 ER PT J AU Verdaguer, V Walsh, TJ Hope, W Cortez, KJ AF Verdaguer, Virginia Walsh, Thomas J. Hope, William Cortez, Karoll J. TI Galactomannan antigen detection in the diagnosis of invasive aspergillosis SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE Aspergillus fumigatus; Aspergillus galactomannan antigen; early diagnosis; therapeutic monitoring ID LINKED-IMMUNOSORBENT-ASSAY; CELL TRANSPLANT RECIPIENTS; LATEX AGGLUTINATION-TEST; RECEIVING PIPERACILLIN-TAZOBACTAM; PULMONARY ASPERGILLOSIS; ENZYME-IMMUNOASSAY; CIRCULATING GALACTOMANNAN; BRONCHOALVEOLAR LAVAGE; NEUTROPENIC PATIENTS; SERUM GALACTOMANNAN AB Invasive aspergillosis is a serious and lethal infection among immunocompromised patients, with reported mortality rates as high as 74-92%. The high mortality is related to the severe immunosuppression experienced by these patients as well as the difficulties for physicians in arriving at a timely diagnosis. Definitive diagnostic procedures (tissue biopsy for histopathology and culture) are often precluded by severe cytopenias and coagulation abnormalities. The development of minimally invasive, nonculture diagnostic methods is a major advance in the early diagnosis of invasive aspergillosis. Galactomannan is a heteropolysaccharide (mannan core and side residues of galactofuranosyl units) present in the cell wall of Aspergillus spp. The double sandwich enzyme immunoassay, which detects galactomannan in serum samples, has been available in Europe for almost a decade and in the USA since May 2003, for the diagnosis of invasive aspergillosis. However, availability of the double galactomannan enzyme immunoassay is center variable in the USA and, although its analytical performance in the diagnosis of invasive aspergillosis is well documented, its routine use in clinical practice is limited. As an adjunct in the diagnosis and management of invasive aspergillosis, incorporation of the galactomannan enzyme immunoassay into clinical trials will help to further define its role. C1 Pediat Oncol Branch, Immunocompromissed Host Sect, NCI, NIH, Bethesda, MD 20892 USA. RP Cortez, KJ (reprint author), Pediat Oncol Branch, Immunocompromissed Host Sect, NCI, NIH, 9000 Rockville Pike 10,Ctr Dr CRC 1-W-5752, Bethesda, MD 20892 USA. EM cortezk@mail.nih.gov OI Hope, William/0000-0001-6187-878X NR 81 TC 33 Z9 37 U1 1 U2 5 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD JAN PY 2007 VL 7 IS 1 BP 21 EP 32 DI 10.1586/14737159.7.1.21 PG 12 WC Pathology SC Pathology GA 131DD UT WOS:000243847500004 PM 17187481 ER PT J AU Kim, YS Choi, DH Block, ML Lorenzl, S Yang, LC Kim, YJ Sugama, S Cho, BP Hwang, O Browne, SE Kim, SY Hong, JS Beal, MF Joh, TH AF Kim, Yoon Seong Choi, Dong Hee Block, Michelle L. Lorenzl, Stefan Yang, Lichuan Kim, Youn Jung Sugama, Shuei Cho, Byung Pil Hwang, Onyou Browne, Susan E. Kim, Soo Yul Hong, Jau-Shyong Beal, M. Flint Joh, Tong H. TI A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation SO FASEB JOURNAL LA English DT Article DE dopamine neuron protection ID PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; NADPH OXIDASE; REACTIVE MICROGLIA; APOPTOSIS; BRAIN; CELLS; MODEL; MPTP; MICE AB Recent studies have demonstrated that activated microglia play an important role in dopamine (DA) neuronal degeneration in Parkinson disease (PD) by generating NADPH-oxidase (NADPHO)-derived superoxide. However, the molecular mechanisms that underlie microglial activation in DA cell death are still disputed. We report here that matrix metalloproteinase-3 (MMP-3) was newly induced and activated in stressed DA cells, and the active form of MMP-3 (actMMP-3) was released into the medium. The released actMMP-3, as well as catalytically active recombinant MMP-3 ( cMMP-3) led to microglial activation and superoxide generation in microglia and enhanced DA cell death. cMMP-3 caused DA cell death in mesencephalic neuron-glia mixed culture of wild-type (WT) mice, but this was attenuated in the culture of NADPHO subunit null mice (gp9(1phox-/-)), suggesting that NADPHO mediated the cMMP-3-induced microglial production of superoxide and DA cell death. Furthermore, in the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- injected animal model of PD, nigrostriatal DA neuronal degeneration, microglial activation, and superoxide generation were largely attenuated in MMP-3-/- mice. These results indicate that actMMP-3 released from stressed DA neurons is responsible for microglial activation and generation of NADPHO-derived superoxide and eventually enhances nigrostriatal DA neuronal degeneration. Our results could lead to a novel therapeutic approach to PD. C1 Cornell Univ, Weill Med Coll, Burke Med Res Inst, White Plains, NY USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, White Plains, NY USA. Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea. NIEHS, Res Triangle Pk, NC 27709 USA. Kyung Hee Univ, Coll Oriental Med, Seoul, South Korea. RP Joh, TH (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, Rm F610,1300 York Ave, New York, NY 10021 USA. EM thjoh@med.cornell.edu NR 27 TC 99 Z9 108 U1 2 U2 8 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 JAN PY 2007 VL 21 IS 1 BP 179 EP 187 DI 10.1096/fj.06-5865com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121AX UT WOS:000243130200019 PM 17116747 ER PT J AU Patchev, AV Fischer, D Wolf, SS Herkenham, M Gotz, F Gehin, M Chambon, P Patchev, VK Almeida, OFX AF Patchev, Alexandre V. Fischer, Dieter Wolf, Siegmund S. Herkenham, Miles Goetz, Franziska Gehin, Martine Chambon, Pierre Patchev, Vladimir K. Almeida, Osborne F. X. TI Insidious adrenocortical insufficiency underlies neuroendocrine dysregulation in TIF-2 deficient mice SO FASEB JOURNAL LA English DT Article DE stress; adrenal cortex; steroidogenesis; hypothalamus; hippocampus ID RECEPTOR MESSENGER-RNA; STEROIDOGENIC FACTOR-I; GLUCOCORTICOID-RECEPTOR; TRANSCRIPTIONAL COACTIVATOR; HORMONE-RECEPTORS; NUCLEAR RECEPTORS; RAT-BRAIN; EXPRESSION; STRESS; SRC-1 AB C The transcription-intermediary-factor-2 (TIF-2) is a coactivator of the glucocorticoid receptor (GR),and its disruption would be expected to influence glucocorticoid-mediated control of the hypothalamo-pituitary-adrenal (HPA) axis. Here, we show that its targeted deletion in mice is associated with altered expression of several glucocorticoid-dependent components of HPA regulation ( e. g., corticotropin-releasing hormone, vasopressin, ACTH, glucocorticoid receptors), suggestive of hyperactivity under basal conditions. At the same time, TIF-2(-/-) mice display significantly lower basal corticosterone levels and a sluggish and blunted initial secretory response to brief emotional and prolonged physical stress. Subsequent analysis revealed this discrepancy to result from pronounced aberrations in the structure and function of the adrenal gland, including the cytoarchitectural organization of the zona fasciculata and basal and stress-induced expression of key elements of steroid hormone synthesis, such as the steroidogenic acute regulatory ( StAR) protein and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). In addition, altered expression levels of two nuclear receptors, DAX-1 and steroidogenic factor 1 (SF-1), in the adrenal cortex strengthen the view that TIF-2 deletion disrupts adrenocortical development and steroid biosynthesis. Thus, hyperactivity of the hypothalamo-pituitary unit is ascribed to insidious adrenal insufficiency and impaired glucocorticoid feedback. C1 Humboldt Univ, Charite, Sch Med, Inst Expt Endocrinol, D-10117 Berlin, Germany. Max Planck Inst Psychiat, Neuroadaptat Grp, D-80804 Munich, Germany. Schering AG, Corp Res Gynecol & Androl, Jena, Germany. NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA. IGBMC, Illkirch Graffenstaden, France. RP Patchev, AV (reprint author), Humboldt Univ, Charite, Sch Med, Inst Expt Endocrinol, Schumannstr 20-21, D-10117 Berlin, Germany. EM alexandre.patchev@charite.de RI Almeida, Osborne/E-8402-2010; OI Almeida, Osborne/0000-0001-7331-6928; Herkenham, Miles/0000-0003-2228-4238 NR 42 TC 14 Z9 14 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2007 VL 21 IS 1 BP 231 EP 238 DI 10.1096/fj.06-6952com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121AX UT WOS:000243130200025 PM 17135362 ER PT J AU Tountas, NA Fortini, ME AF Tountas, Nikolaos A. Fortini, Mark E. TI Drosophila as a Model for Human Diseases - IRB and ICREA, Barcelona, Spain, October 5-7, 2006 SO FLY LA English DT Article DE addiction; ageing; cancer; cardiovascular; disease model; neurodegeneration; neurological disorder; tumor suppressor ID DEPENDENT KINASE INHIBITOR; NEURODEGENERATIVE DISEASE; PARKIN MUTANTS; SELF-RENEWAL; HUMAN CANCER; CELL-CYCLE; LIFE-SPAN; PROTEIN; GENE; PROLIFERATION C1 [Tountas, Nikolaos A.; Fortini, Mark E.] Natl Canc Inst Frederick, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Tountas, NA (reprint author), Natl Canc Inst Frederick, Canc & Dev Biol Lab, 1050 Boyles St, Frederick, MD 21702 USA. EM tountasn@ncifcrf.gov; fortini@ncifcrf.gov NR 49 TC 3 Z9 3 U1 2 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1933-6934 J9 FLY JI Fly PD JAN-FEB PY 2007 VL 1 IS 1 BP 47 EP 54 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 307WM UT WOS:000256349700008 PM 18690062 ER PT J AU Simeckova, K Brozova, E Vohanka, J Pohludka, M Kostrouch, Z Krause, MW Rall, JE Kostrouchova, M AF Simeckova, K. Brozova, E. Vohanka, J. Pohludka, M. Kostrouch, Z. Krause, M. W. Rall, J. E. Kostrouchova, M. TI Supplementary nuclear receptor NHR-60 is required for normal embryonic and early larval development of Caenorhabditis elegans SO FOLIA BIOLOGICA LA English DT Article DE Caenorhabditis elegans; nuclear hormone receptor; development; NHR-23 ID THYROID-HORMONE RECEPTOR; GENE-EXPRESSION; C-ELEGANS; LIGAND-BINDING; HEPATOCYTE DIFFERENTIATION; COFACTOR RECRUITMENT; VISCERAL ENDODERM; CENTRAL REGULATOR; LIVING CELLS; F-DOMAIN AB The C. elegans genome encodes an unexpectedly large number of NHRs, the majority of which are classified as supplementary nuclear receptors (supnrs) that are likely to have evolved from an ancestral protein related to vertebrate HNF-4. To understand the need for this large repertoire of potential ligand-activated transcription factors, we have begun to study an 18-member subgroup defined by DNA binding domain relatedness. Here we report on NHR-60, a supnr expressed ubiquitously throughout development with a distinct pattern of localization on the nuclear periphery. Both antibody staining and GFP reporter genes demonstrated high-level expression and accumulation of NHR-60 in seam cell nuclei that is dependent on NHR-23 activity. Interference with NHR-60 activity, by either RNAi or overexpression of a putative dominant negative isoform, results in embryonic and early larval lethality, including defects in seam cell development. This adds NHR-60 to the list of C. elegans NHRs playing important roles in development. C1 Charles Univ Prague, Lab Mol Biol & Genet, Fac Med 1, Prague 12801 2, Czech Republic. Charles Univ Prague, Lab Mol Pathol, Inst Inherited Metab Disorders, Fac Med 1, Prague 12801 2, Czech Republic. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kostrouchova, M (reprint author), Charles Univ Prague, Lab Mol Biol & Genet, Fac Med 1, Ke Karlovu 2, Prague 12801 2, Czech Republic. EM marta.kostrouchova@lfl.cuni.cz OI Krause, Michael/0000-0001-6127-3940 FU Intramural NIH HHS NR 57 TC 8 Z9 10 U1 0 U2 1 PU CHARLES UNIV PRAGUE, FIRST FACULTY MEDICINE PI PRAGUE 6 PA FLEMINGOVO NAM. 2, PRAGUE 6 166 37, CZECH REPUBLIC SN 0015-5500 J9 FOLIA BIOL-PRAGUE JI Folia Biol.-Prague PY 2007 VL 53 IS 3 BP 85 EP 96 PG 12 WC Biochemistry & Molecular Biology; Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Oncology; Cell Biology GA 181MR UT WOS:000247441300004 PM 17579999 ER PT J AU Horn, TL Cwik, MJ Morrissey, RL Kapetanovic, I Crowell, JA Booth, TD McCormick, DL AF Horn, T. L. Cwik, M. J. Morrissey, R. L. Kapetanovic, I. Crowell, J. A. Booth, T. D. McCormick, D. L. TI Oncogenicity evaluation of resveratrol in p53((+/-)) (p53 knockout) mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE resveratrol; cancer chemopreventive agent; oncogenicity; p53((+/-)) mouse ID CHEMOPREVENTIVE AGENT RESVERATROL; CANCER CELLS; LIFE-SPAN; A/J MICE; IN-VITRO; RATS; GROWTH; MOUSE; CYCLOOXYGENASE-2; APOPTOSIS AB A six-month study was conducted in p53((+/-)) mice to evaluate the possible oncogenicity of resveratrol (3,5,4'-trihydroxy-trans-stilbene), a cancer chemopreventive agent present in grapes and other foods. p53((+/-)) mice (25/sex/group) received daily gavage exposure to vehicle only (negative control), resveratrol doses of 1000, 2000, or 4000 mg/kg/day, or p-cresidine (400 mg/kg/day; positive control). No mortality was seen in mice receiving the low dose of resveratrol. However, the mid and high doses induced mortality associated with impaction of the test article in the gastrointestinal tract. Resveratrol had no effect on body weight, food consumption, or clinical signs in surviving mice in any dose group, but induced dose-related increases in liver weight and serum cholesterol in both sexes. Mild anemia was seen in male mice at the high dose only; hematologic effects were not seen in females. Histopathology identified the kidney (hydronephrosis) and urinary bladder (epithelial hyperplasia) as target tissues for resveratrol toxicity. The incidences of both benign and malignant tumors in mice exposed to resveratrol were comparable to those in vehicle controls. By contrast, the positive control article, p-cresidine, induced urinary bladder cancer in both sexes. When administered to p53((+/-)) mice at its maximum tolerated dose, resveratrol demonstrates no evidence of oncogenicity. (c) 2006 Elsevier Ltd. All rights reserved. C1 IIT, Res Inst, Life Sci Grp, Chicago, IL 60616 USA. Pathol Assoc, Chicago, IL 60612 USA. NCI, Bethesda, MD 20892 USA. Royalmt Pharma, Montreal, PQ H4P 2T4, Canada. RP McCormick, DL (reprint author), IIT, Res Inst, Life Sci Grp, 10 W 35th St, Chicago, IL 60616 USA. EM dmccormick@iitri.org FU NCI NIH HHS [N01-CN-05135, N01 CN005135-000] NR 42 TC 24 Z9 26 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2007 VL 45 IS 1 BP 55 EP 63 DI 10.1016/j.fct.2006.07.015 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 125KR UT WOS:000243441300007 PM 16965847 ER PT J AU Arao, Y Kanamori, N Kikkawa, E Otsuka, H Arimoto, Y Ikeda, K Inakuma, T Kayama, F AF Arao, Yukitomo Kanamori, Namiko Kikkawa, Eri Otsuka, Hiroko Arimoto, Yasushi Ikeda, Kazuhiro Inakuma, Takahiro Kayama, Fujio TI A two-step screening method, using estrogen receptor-mediated transactivation, to measure estrogenicity in edible plants SO FOOD CHEMISTRY LA English DT Article DE phytoestrogen; estrogen receptor; transcription; screening ID POMEGRANATE PUNICA-GRANATUM; BREAST-CANCER; PHYTOESTROGENS; GENISTEIN; BETA; ALPHA; AGONISTS/ANTAGONISTS; PHOSPHORYLATION; CHEMICALS AB Estrogenic activity in 88 edible plants was screened using a human ovarian carcinoma cell line stably transformed with estrogen-responsive elements (ERE) fused to a luciferase (luc) reporter gene (BG1Luc4E(2)). We found 18 plants (ashitaba, avocados, chinese mustard, chinese chive (yellow), chrysanthemum, dokudami, shantung greens, green soybeans, soybean seeds, soybean sprouts, hop, japanese pepper, kidney beans, kuromame, perilla, peas (immature), plantain, and pomegranate juice) expressing estrogenic activity in BGILuc4E(2) cells. To confirm that the phytoestrogenic activity occurred via estrogen receptors (ER), the reporter vector (ERE-tk-luc) and an expression vector, containing either ER alpha or ER beta, were used to transiently transfect 293T cells. Extracts from avocados, plantain and dokudami did not activate ER alpha- and ER beta-mediated transcription. In conclusion, we report a simple and quick screening method for phytoestrogenic activity in plant extracts using BGILuc4E(2) cells and confirmation of the results by ER alpha- or ER beta-transfected 293T cells. This two-step screening method has a practical application in screening estrogenic substances in edible plants. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Jichi Med Univ, Ctr Community Med, Dept Environm Med, Shimotsuke, Tochigi 3290498, Japan. Kagome Co Ltd, Inst Res, Tochigi 3292792, Japan. Japan Sci & Technol Corp, CREST, Kawaguchi, Saitama 3320012, Japan. RP Arao, Y (reprint author), NIEHS, Reprod & Dev Toxicol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM araoy@niehs.nih.gov; kayamaf@jichi.ac.jp NR 19 TC 0 Z9 0 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PY 2007 VL 104 IS 3 BP 1288 EP 1294 DI 10.1016/j.foodchem.2007.01.076 PG 7 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 179FS UT WOS:000247275700053 ER PT J AU Brown, P Detwiler, LA AF Brown, Paul Detwiler, Linda A. BE Doyle, MP Beuchat, LR TI Bovine Spongiform Encephalopathy: Consequences for Human Health SO FOOD MICROBIOLOGY: FUNDAMENTALS AND FRONTIERS, THIRD EDITION LA English DT Article; Book Chapter ID CREUTZFELDT-JAKOB-DISEASE; PEDIGREE SUCKLER COWS; RENDERING PROCEDURES; PRION PROTEIN; SCRAPIE VIRUS; RISK-FACTORS; FEED BAN; BLOOD-TRANSFUSION; GREAT-BRITAIN; BSE C1 [Brown, Paul] NIH, Bethesda, MD 20814 USA. [Detwiler, Linda A.] Virginia Maryland Reg Coll Vet Med, Ctr Publ & Corp Vet Med, College Pk, MD 20742 USA. RP Brown, P (reprint author), NIH, Bethesda, MD 20814 USA. NR 63 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-407-6 PY 2007 BP 611 EP 626 PG 16 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ57 UT WOS:000279003400029 ER PT J AU Hayunga, EG AF Hayunga, Eugene G. BE Doyle, MP Beuchat, LR TI Helminths Acquired from Finfish, Shellfish, and Other Food Sources SO FOOD MICROBIOLOGY: FUNDAMENTALS AND FRONTIERS, THIRD EDITION LA English DT Article; Book Chapter ID HUMAN INFECTION; EOSINOPHILIC MENINGOENCEPHALITIS; ANGIOSTRONGYLUS-CANTONENSIS; PARASITIC INFECTION; FASCIOLA-HEPATICA; ANISAKIS-SIMPLEX; LARVA MIGRANS; TRANSMISSION; NEMATODA; DISEASE C1 NICHHD, Off Extramural Policy, NIH, Bethesda, MD 20892 USA. RP Hayunga, EG (reprint author), NICHHD, Off Extramural Policy, NIH, Bethesda, MD 20892 USA. NR 76 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-407-6 PY 2007 BP 649 EP 662 PG 14 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ57 UT WOS:000279003400031 ER PT J AU Elkins, KL Cowley, SC Bosio, CM AF Elkins, Karen L. Cowley, Siobhan C. Bosio, Catharine M. TI Innate and adaptive immunity to Francisella SO FRANCISELLA TULARENSIS: BIOLOGY, PATHOGENICITY, EPIDEMIOLOGY, AND BIODEFENSE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE Francisella; T lymphocyte; B lymphocyte; macrophage; dendritic cell; natural killer cell; cytokine; chemokine; protective immunity ID LIVE VACCINE STRAIN; VIRULENT TYPE-A; CELL-MEDIATED-IMMUNITY; NECROSIS-FACTOR-ALPHA; LABORATORY-ACQUIRED TULAREMIA; LIPOPOLYSACCHARIDE O-ANTIGEN; INTRANASAL INTERLEUKIN-12 TREATMENT; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; FORMERLY YERSINIA-PHILOMIRAGIA; CHRONIC GRANULOMATOUS-DISEASE AB Studies of immune responses to Francisella have been conducted for well over 50 years. Here, the basic parameters of innate and adaptive immune responses to Francisella are reviewed, with an emphasis on those that may contribute directly to protection against infection. Although older literature provides a wealth of information on human immune responses to infection and vaccination, most recent information has been derived largely from studies in animals and using animal cells, particularly mice. In experimental animals, activation of macrophages, a major and probably preferred host cell for Francisella, appears central to control of infection. Thus, in animal models and in vitro studies using mouse macrophages, cytokines such as IFN-gamma and TNF-alpha, derived first from both nonspecific cells such as natural killer cells and later from Francisella-specific T cells, collaborate to effect intracellular killing. In mice, these intracellular killing mechanisms include reactive nitrogen and oxygen species, but killing mechanisms remain to be identified in humans. Ultimately both CD4(+) and CD8(+) T cells develop into Francisella-specific memory cells and are important for control of primary Francisella infection or vaccination-induced protection. The effector mechanisms invoked by either CD4+ or CD8+ T cells, beyond production of IFN-gamma and TNF-alpha, are the subject of ongoing studies. Both specific antibodies and B cells may contribute to control of primary infection or vaccination-induced protection in some circumstances, particularly against lower virulence Francisella strains. Thus a number of known proinflammatory and Th-1 T cell related components of the immune system combat this virulent bacterium; no doubt others remain to be discovered. C1 LMDCI, Bethesda, MD 20892 USA. US FDA, Div Bacterial Parasit & Allergen Prod, Lab Mycobacteriol Dis & Cellular Immunol, Bethesda, MD 20014 USA. NIAID, NIH, Lab Intracellular Parasites, Hamilton, MT USA. RP Elkins, KL (reprint author), LMDCI, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM karen.elkins@fda.hhs.gov RI Bosio, Catharine/D-7456-2015 NR 161 TC 108 Z9 108 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1105 BP 284 EP 324 DI 10.1196/annals.1409.014 PG 41 WC Medicine, Research & Experimental; Multidisciplinary Sciences SC Research & Experimental Medicine; Science & Technology - Other Topics GA BGM15 UT WOS:000248298500013 PM 17468235 ER PT J AU Bhattacharjee, S Deterding, LJ Jiang, J Bonini, MG Tomer, K Ramirez, DC Mason, RP AF Bhattacharjee, Suchandra Deterding, Leesa J. Jiang, Jinyie Bonini, Marcello G. Tomer, Kenneth Ramirez, Dario C. Mason, Ronald P. TI Electron transfer between a tyrosyl radical and a cysteine residue in hemoproteins: Spin trapping analysis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Bhattacharjee, Suchandra; Deterding, Leesa J.; Jiang, Jinyie; Bonini, Marcello G.; Tomer, Kenneth; Ramirez, Dario C.; Mason, Ronald P.] NIEHS, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S13 EP S14 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900027 ER PT J AU Bilski, P Risek, B Chignell, CF Schrader, WT AF Bilski, Piotr Risek, Boris Chignell, Colin F. Schrader, William T. TI Photocytotoxicity and photochemistry of the selective non-steroidal androgen receptor modulator TDPQ SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Bilski, Piotr; Chignell, Colin F.] NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. [Risek, Boris; Schrader, William T.] NIEHS, NIH, Lab Reprod & Dev Toxicol, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S126 EP S126 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900339 ER PT J AU Bonini, MG Stadler, K Silva, SO Corbett, J Dore, M Petranka, J Duma, D Fernandes, DC Tanaka, LY Laurindo, FRM Mason, RP AF Bonini, Marcelo G. Stadler, Krisztian Silva, Sueli O. Corbett, Jean Dore, Michael Petranka, John Duma, Danielle Fernandes, Denise C. Tanaka, Leonardo Y. Laurindo, Francisco R. M. Mason, Ronald P. TI Constitutive nitric oxide synthase activation is a significant route mediating nitroglycerin-induced vasodilation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Bonini, Marcelo G.; Stadler, Krisztian; Silva, Sueli O.; Corbett, Jean; Dore, Michael; Petranka, John; Duma, Danielle; Mason, Ronald P.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Fernandes, Denise C.; Tanaka, Leonardo Y.; Laurindo, Francisco R. M.] Univ Sao Paulo, Inst Heart, Sao Paulo, SP, Brazil. RI Laurindo, Francisco/J-6575-2015 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S164 EP S164 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900447 ER PT J AU Bonini, MG Raines, KW Mason, RP Campbell, SL AF Bonini, Marcelo G. Raines, Kimberly W. Mason, Ronald P. Campbell, Sharon L. TI P21(Ras) cysteine 118 thiyl radical formation as an obligatory intermediate in nitric oxide mediated guanine nucleotide exchange SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Bonini, Marcelo G.; Mason, Ronald P.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Raines, Kimberly W.; Campbell, Sharon L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S148 EP S148 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900397 ER PT J AU Bonini, MG Mason, RP AF Bonini, Marcelo G. Mason, Ronald P. TI Guanosine monophosphate, but not guanosine and its higher phosphate congeners, mediates heme-periphery electron transfers in lactoperoxidase SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Bonini, Marcelo G.; Mason, Ronald P.] NIEHS, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S22 EP S22 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900053 ER PT J AU Chen, Q Sun, AY Espey, MG Levine, M AF Chen, Qi Sun, Andrew Y. Espey, Michael Graham Levine, Mark TI Ascorbic acid as a pro-oxidant therapeutic agent in cancer SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Chen, Qi; Sun, Andrew Y.; Espey, Michael Graham; Levine, Mark] NIDDK, Natl Inst Hlth, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S52 EP S52 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900133 ER PT J AU Isbell, TS Gladwin, MT Patel, RP AF Isbell, T. Scott Gladwin, Mark T. Patel, Rakesh P. TI Deoxyhemoglobin possesses dual functions as NO scavenger and a nitrite dependent NO generator: Insights from oxygen controlled vessel bioassays SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 Univ Alabama, Dept Pathol, Tuscaloosa, AL 35487 USA. Univ Alabama, Ctr Free Rad Biol, Tuscaloosa, AL 35487 USA. [Gladwin, Mark T.] NHLBI, Vasc Med Branch, Dept Crit Care Med, NIH, Bethesda, MD 20892 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S167 EP S167 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900457 ER PT J AU Jacobs, KM Gius, D AF Jacobs, Kristi Muldoon Gius, David TI Superoxide levels and mitochondrial function are regulated by SIRT3 SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Jacobs, Kristi Muldoon; Gius, David] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S156 EP S156 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900425 ER PT J AU Kadiiska, MB Liu, J Waalkes, M Mason, RP AF Kadiiska, Maria B. Liu, Jie Waalkes, Mike Mason, Ronald P. TI Free radical production by arsenic trioxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Kadiiska, Maria B.; Mason, Ronald P.] NIEHS, NCI, NIH, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S56 EP S57 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900148 ER PT J AU Keszler, A Piknova, B Schechter, AN Hogg, N AF Keszler, Agnes Piknova, Barbora Schechter, Alan N. Hogg, Neil TI The mechanism of reaction between oxyhemoglobin and nitrite SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Keszler, Agnes; Hogg, Neil] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Piknova, Barbora; Schechter, Alan N.] NIDDK, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S15 EP S15 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900032 ER PT J AU Lao, S Levine, RL AF Lao, Shen Levine, Rodney L. TI Testing the hypothesis that "Methionine residues in proteins are antioxidants" SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Lao, Shen; Levine, Rodney L.] NHLBI, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S112 EP S112 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900300 ER PT J AU Mason, RR AF Mason, Ronald R. TI Do-it-yourself detection of protein and DNA free radicals in organelles, cells, and tissues: A 30 year Odyssey SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Mason, Ronald R.] NIEHS, NIH, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S1 EP S1 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900003 ER PT J AU Noda, Y Berlett, B Stodtman, ER Aponte, A Morgan, M Shen, RF AF Noda, Yasuko Berlett, Barbara Stodtman, Earl R. Aponte, Angel Morgan, Meghan Shen, Rong-Fong TI Specificity of carbonylated proteins in E-coli under certain nutrient conditions: Proteomic identification SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Noda, Yasuko; Berlett, Barbara; Stodtman, Earl R.] NIH, NHLBI, Bethesda, MD USA. [Aponte, Angel; Morgan, Meghan; Shen, Rong-Fong] NIH, NHLBI, PCF, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S113 EP S113 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900303 ER PT J AU Perwe-Hussain, S He, PJ Subleski, J Hofseth, LJ Trivers, G Mechanic, L Bailey, A Bernard, M Schwank, J Djurickovic, D Haines, D Weiss, J Laubach, V Back, T Wiltrout, RH Harris, CC AF Perwe-Hussain, S. He, Peijun Subleski, Jeffery Hofseth, Lorne J. Trivers, Glennwood Mechanic, Leah Bailey, Anne Bernard, Mark Schwank, Jonathan Djurickovic, Draginja Haines, Diana Weiss, Jonathan Laubach, Victor Back, Timothy Wiltrout, Robert H. Harris, Curtis C. TI Chronic inflammation and cancer: Influence of nitric oxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Perwe-Hussain, S.; He, Peijun; Subleski, Jeffery; Trivers, Glennwood; Mechanic, Leah; Bernard, Mark; Schwank, Jonathan; Djurickovic, Draginja; Weiss, Jonathan; Back, Timothy; Wiltrout, Robert H.; Harris, Curtis C.] NCI, Bethesda, MD 20892 USA. [Hofseth, Lorne J.; Bailey, Anne] Univ S Carolina, Columbia, SC 29208 USA. [Haines, Diana] Univ Virginia, Ctr Hlth Sci, Charlottesville, VA 22903 USA. RI Laubach, Victor/E-8818-2015 OI Laubach, Victor/0000-0001-9673-5383 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S55 EP S55 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900143 ER PT J AU Piknova, B Schechter, AN AF Piknova, Barbora Schechter, Alan N. TI The hemoglobin - Haptoglobin complex and its reaction with nitrite in plasma SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Piknova, Barbora; Schechter, Alan N.] 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S169 EP S169 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900465 ER PT J AU Quon, MJ AF Quon, Michael J. TI Mechanisms underlying beneficial effects of green tea polyphenols on metabolic and cardiovascular health SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Quon, Michael J.] NCCAM, NIH, Bethesda, MD USA. RI Quon, Michael/B-1970-2008 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S9 EP S9 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900019 ER PT J AU Ramirez, DC Gomez-Mejiba, SE Corbett, JT Mason, RP AF Ramirez, Dario C. Gomez-Mejiba, Sandra E. Corbett, Jean T. Mason, Ronald P. TI A radical view of Cu, Zn-superoxide dismutase-driven oxidations: Copper- and carbonate radical anion-triggered protein radical chemistry SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Ramirez, Dario C.; Gomez-Mejiba, Sandra E.; Corbett, Jean T.; Mason, Ronald P.] NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S114 EP S114 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900308 ER PT J AU Ranguelova, K Suarez, J Gerfen, GJ Magliozzo, ARS AF Ranguelova, Kalina Suarez, Javier Gerfen, Gary J. Magliozzo, Ann Richard S. TI Radical sites in M-tuberculosis KatG identified using Epr spectroscopy, the 3-D crystal structure and electron-transfer couplings SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Ranguelova, Kalina] NIEHS, Bethesda, MD 20892 USA. [Suarez, Javier; Magliozzo, Ann Richard S.] CUNY Brooklyn Coll, Brooklyn, NY 11210 USA. [Gerfen, Gary J.] Albert Einstein Coll Med, Bronx, NY 10461 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S26 EP S26 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900067 ER PT J AU Rao, VA Klein, S Zielonka, J Kalvanaraman, B Shacter, E AF Rao, V. Ashutosh Klein, Sarah Zielonka, Jacek Kalvanaraman, B. Shacter, Emily TI The mitochondrially-targeted redox agent mitoquinone enhances doxorubicin-induced toxicity to breast cancer cells while protecting cardiac myocytes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Rao, V. Ashutosh] NCI, Natl Canc Inst, FDA, IOFF Program, Bethesda, MD 20892 USA. [Klein, Sarah; Shacter, Emily] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Zielonka, Jacek; Kalvanaraman, B.] Med Coll Wisconsin, Milwaukee, WI USA. RI Zielonka, Jacek/N-9546-2014 OI Zielonka, Jacek/0000-0002-2524-0145 NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S59 EP S59 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900156 ER PT J AU Scarbrough, P Mattson, DM Aykin-Burns, N Gius, D Spitz, DR AF Scarbrough, Peter Mattson, David M. K. Aykin-Burns, Nukhet Gius, David Spitz, Douglas R. TI 2-deoxy-D-glucose and 17-(allylamino)-17-demethoxygeldanamycin enhances toxicity as well as increases parameters indicative of oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Scarbrough, Peter; Mattson, David M. K.; Aykin-Burns, Nukhet; Spitz, Douglas R.] Univ Iowa, Iowa City, IA 52242 USA. [Gius, David] 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S59 EP S59 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900157 ER PT J AU Shiva, S Curtis, E Liu, G Gladwin, MT AF Shiva, Sruti Curtis, Erin Liu, Geng Gladwin, Mark T. TI Tissue dependent nitrite metabolism and NO production is regulated by oxygen SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Shiva, Sruti; Curtis, Erin; Liu, Geng; Gladwin, Mark T.] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S80 EP S80 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900207 ER PT J AU Siraki, AG Bonini, MG Jiang, JJ Ehrenshaft, M Mason, RP AF Siraki, Arno G. Bonini, Marcelo G. Jiang, JinJie Ehrenshaft, Marilyn Mason, Ronald P. TI Procainamide, but not N-acetylprocain-amide, induces protein free radical formation on myeloperoxidase: A potential mechanism of agranulocytosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Siraki, Arno G.; Bonini, Marcelo G.; Jiang, JinJie; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Lab Pharmacol & Chem, NIH, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S116 EP S116 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900314 ER PT J AU Stadler, K Bonini, MG Mason, RP Kadiiska, MB AF Stadler, Kristian Bonini, Marcelo G. Mason, Ronald P. Kadiiska, Maria B. TI Key role of inducible nitric oxide synthase in free radical production and protein oxidation induced by ketosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Stadler, Kristian; Bonini, Marcelo G.; Mason, Ronald P.; Kadiiska, Maria B.] NIH, NIEHS, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S171 EP S171 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900472 ER PT J AU Stadler, K Bonini, MG Dallas, S Radi, R Mason, RP Kadiiska, MB AF Stadler, Krisztian Bonini, Marcelo G. Dallas, Shannon Radi, Rafael Mason, Ronald P. Kadiiska, Maria B. TI Inducible nitric oxide synthase overexpression in diabetic target organs triggers increased lipid peroxidation and tissue damage SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Stadler, Krisztian; Bonini, Marcelo G.; Dallas, Shannon; Mason, Ronald P.; Kadiiska, Maria B.] NIH, NIEHS, Bethesda, MD 20892 USA. [Radi, Rafael] Univ Republ Uruguay, Fac Med, Dept Bioquim, Montevideo, Uruguay. 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S171 EP S171 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900473 ER PT J AU Tanaka, M Chock, PB Stadtman, ER AF Tanaka, Mikiei Chock, P. Boon Stadtman, Earl R. TI Oxidative interaction between RNA and cytochrome C SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Tanaka, Mikiei; Chock, P. Boon; Stadtman, Earl R.] NHLBI, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S72 EP S72 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900188 ER PT J AU Towner, RA Smith, N Saunders, D Henderson, M Hensley, K West, M Lupu, F Bonini, M Mason, R AF Towner, Rheal Antoine Smith, Nataliya Saunders, Debra Henderson, Michael Hensley, Kenneth West, Melinda Lupu, Florea Bonini, Marcelo Mason, Ronald TI In vivo detection of DMPO-adducts using molecular targeted MRI SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Towner, Rheal Antoine; Smith, Nataliya; Saunders, Debra; Henderson, Michael; Hensley, Kenneth; West, Melinda; Lupu, Florea] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Bonini, Marcelo; Mason, Ronald] NIEHS, Res Triangle Pk, NC 27709 USA. RI Lupu, Florea/C-3162-2009 OI Lupu, Florea/0000-0003-1249-9278 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S179 EP S180 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900495 ER PT J AU Wang, J Espey, MG Levine, M AF Wang, Jin Espey, Michael Graham Levine, Mark TI Gene expression analysis of lymphoma cell resistance to cytotoxicity induced by pharmacological ascorbate SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Wang, Jin; Espey, Michael Graham; Levine, Mark] NIDDK, Mol & Clin Nutr Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S160 EP S160 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900439 ER PT J AU Zhao, B Bilski, PJ He, YY Feng, L Chignell, CF AF Zhao, Baozhong Bilski, Piotr J. He, Yu-Ying Feng, Li Chignell, Colin F. TI Photo-induced reactive oxygen species generation and cytotoxicity of different water-soluble fullerenes in human HaCaT keratinocytes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 14th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 14-18, 2007 CL Washington, DC SP Soc Free Rad Biol & Med C1 [Zhao, Baozhong; Bilski, Piotr J.; He, Yu-Ying; Feng, Li; Chignell, Colin F.] NIEHS, NIH, Lab Pharmacol & Chem, 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2007 VL 43 SU 1 BP S128 EP S128 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 229WC UT WOS:000250835900344 ER PT J AU Feyder, M Wiedholz, L Sprengel, R Holmes, A AF Feyder, Michael Wiedholz, Lisa Sprengel, Rolf Holmes, Andrew TI Impaired associative fear learning in mice with complete loss or haploinsufficiency of AMPA GluR1 receptors SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE glutamate; learning; GluR1; AMPA; mouse AB There is compelling evidence that L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) glutamate receptors containing the GluR1 subunit contribute to the molecular mechanisms associated with learning. AMPA GluR1 glutamate receptor knockout mice (KO) exhibit abnormal hippocampal and amygdala plasticity, and deficits on various assays for cognition including Pavlovian fear conditioning. Here we examined associative fear learning in mice with complete absence (KO) or partial loss (heterozygous mutant, HET) of GluR1 on multiple fear conditioning paradigms. After multi-trial delay or trace conditioning, KO displayed impaired tone and context fear recall relative to WT, whereas HET were normal. After one-trial delay conditioning, both KO and HET showed impaired tone and context recall. HET and KO showed normal nociceptive sensitivity in the hot plate and tail flick tests. These data demonstrate that the complete absence of GluR1 subunit-containing receptors prevents the formation of associative fear memories, while GluR1 haploinsufficiency is sufficient to impair one-trial fear learning. These findings support growing evidence of a major role for GluR1-containing AMPA receptors in amygdala-mediated forms of learning and memory. C1 [Feyder, Michael; Wiedholz, Lisa; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Sprengel, Rolf] Max Planck Inst Med Res, D-69120 Heidelberg 1, Germany. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov FU National Institute on Alcohol Abuse and Alcoholism FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism Intramural Research Program. NR 52 TC 8 Z9 9 U1 0 U2 1 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5153 J9 FRONT BEHAV NEUROSCI JI Front. Behav. Neurosci. PY 2007 VL 1 AR 4 DI 10.3389/neuro.08/004.2007 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V18VC UT WOS:000208031300003 PM 18958186 ER PT J AU Yang, M Scattoni, ML Zhodzishsky, V Chen, T Caldwell, H Young, WS McFarlane, HG Crawley, JN AF Yang, Mu Scattoni, Maria Luisa Zhodzishsky, Vladimir Chen, Thomas Caldwell, Heather Young, W. Scott, III McFarlane, Hewlet G. Crawley, Jacqueline N. TI Social approach behaviors are similar on conventional versus reverse lighting cycles, and in replications across cohorts, in BTBR T+ tf/J, C57BL/6J, and vasopressin receptor 1B mutant mice SO FRONTIERS IN BEHAVIORAL NEUROSCIENCE LA English DT Article DE inbred strains of mice; BTBR T plus tf/J; C57BL/6J; vasopressin receptor subtype 1b; social interaction; juvenile play; circadian phase; autism AB Mice are a nocturnal species, whose social behaviors occur primarily during the dark phase of the circadian cycle. However, laboratory rodents are frequently tested during their light phase, for practical reasons. We investigated the question of whether light phase testing presents a methodological pitfall for investigating mouse social approach behaviors. Three lines of mice were systematically compared. One cohort of each line was raised in a conventional lighting schedule and tested during the light phase, under white light illumination; another cohort was raised in a reverse lighting schedule and tested during their dark phase, under dim red light. Male C57BL/6J (B6) displayed high levels of sociability in our three-chambered automated social approach task when tested in either phase. BTBR T+ tf/J (BTBR) displayed low levels of sociability in either phase. Five cohorts of vasopressin receptor subtype 1b (Avpr1b) null mutants, heterozygotes, and wildtype littermate controls were tested in the same social approach paradigm: three in the dark phase and two in the light phase. All three genotypes displayed normal sociability in four out of the five replications. In the juvenile play test, testing phase had no effect on play soliciting behaviors in Avpr1b mice, but had modest effects on nose sniff and huddling. Taken together, these findings indicate that testing phase is not a crucial factor for studying some forms of social approach in juvenile and adult mice. C1 [Yang, Mu] NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Scattoni, Maria Luisa] Ist Super Sanita, Dept Cell Biol & Neurosci, Rome, Italy. [Caldwell, Heather; Young, W. Scott, III] NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA. [McFarlane, Hewlet G.] Kenyon Coll, Dept Psychol, Gambier, OH USA. RP Yang, M (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, NIH, Bldg 35,Room 1C-909,Mail Code 3730, Bethesda, MD 20892 USA. EM yangmu@mail.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU National Institute of Mental Health [Z01-MH-02179, Z01-MH-002498-17] FX We thank Ms. Tabitha Morris, NIMH, for her assistance in conducting components of the experiments shown in Figure 4 and Mr. James Heath, NIMH, for genotyping the Avpr1b mice. This research work was supported by the National Institute of Mental Health Intramural Research Program, Z01-MH-02179 (JNC) and Z01-MH-002498-17 (WSY, HC). NR 47 TC 59 Z9 59 U1 1 U2 9 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5153 J9 FRONT BEHAV NEUROSCI JI Front. Behav. Neurosci. PY 2007 VL 1 AR 1 DI 10.3389/neuro.08/001.2007 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V18VC UT WOS:000208031300001 PM 18958184 ER PT J AU Giam, CZ Jeang, KT AF Giam, Chou-Zen Jeang, Kuan-Teh TI HTLV-1 Tax and adult T-cell leukemia SO FRONTIERS IN BIOSCIENCE LA English DT Review DE HTLV-1 Tax; adult T cell leukemia; anaphase promoting complex; cell cycle; chromosome instability; phosphoinositide 3-kinase; NF-kappa B; review ID VIRUS TYPE-I; NF-KAPPA-B; TRANSCRIPTIONAL ACTIVATOR TAX; ANAPHASE-PROMOTING COMPLEX; CREB BINDING-PROTEIN; LONG TERMINAL REPEAT; ONCOGENE PRODUCT TAX; ALPHA IKK-ALPHA; TYPE-1 TAX; MITOTIC CHECKPOINT AB Human T- lymphotropic virus type I ( HTLV- 1) is the etiological agent of adult T- cell leukemia/ lymphoma ( ATL) and HTLV- 1 associated myelopathy/ tropical spastic paraparesis ( HAM/ TSP). HTLV- 1 viral transactivator/ oncoprotein, Tax, activates viral transcription and usurps regulatory mechanisms that are critical for cell growth and division to facilitate viral replication. The effects that Tax exerts on cells include potent NF-.B activation, cell cycle perturbation and cell transformation. How Tax influences ATL development is incompletely understood at present. While Tax- expression is needed at the early stages of cellular transformation, at later times most ATL cells do not express tax; therefore, genetic and epigenetic changes in HTLV- 1- infected cells are believed to play an important role in the etiology of ATL. This review attempts to integrate recent literature on the biological activities of Tax and the properties of HTLV- 1 transformed T- cells and ATL cells, and speculate on what cellular changes may collaborate with Tax to effect cell transformation and ATL development. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Giam, CZ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM cgiam@usuhs.mil RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS; NCI NIH HHS [R01CA115884, R01CA75688] NR 129 TC 61 Z9 65 U1 0 U2 4 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2007 VL 12 BP 1496 EP 1507 DI 10.2741/2163 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 129QS UT WOS:000243745000120 PM 17127397 ER PT J AU Hasenkrug, KJ Dittmer, U AF Hasenkrug, Kim J. Dittmer, Ulf TI Immune control and prevention of chronic Friend retrovirus infection SO FRONTIERS IN BIOSCIENCE LA English DT Article DE Friend retrovirus; cytotoxic T cells regulatory; vaccination; response; chronic; infection; review ID REGULATORY T-CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO PROLIFERATION; MURINE LEUKEMIA-VIRUS; GAMMA-INTERFERON; HIV-INFECTION; VIRAL LOAD; INDUCED ERYTHROLEUKEMIA; EFFECTOR FUNCTIONS; LYMPHOID-TISSUE AB T cells are critical to control acute infection of a host with retroviruses but they are usually unable to prevent the development of chronic infections. This review summarizes studies from the Friend virus mouse model that reveal some of the mechanisms by which T cells control chronic retroviral infection, and also reveal why these responses ultimately fail to fully eradicate infection. Also summarized are findings from vaccine studies demonstrating the immunological requirements for the prevention of chronic retroviral infection. The implications of these findings for chronic infections in humans are discussed. C1 Univ Klinikum Essen, Inst Virol, D-45122 Essen, Germany. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Dittmer, U (reprint author), Univ Klinikum Essen, Inst Virol, D-45122 Essen, Germany. EM ulf.dittmer@uni-essen.de NR 57 TC 33 Z9 33 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2007 VL 12 BP 1544 EP 1551 DI 10.2741/2167 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 129QS UT WOS:000243745000124 PM 17127401 ER PT J AU Stahl-Hennig, C Eisenblatter, M Franz, M Stoiber, H Tenner-Racz, K Suh, YS Jasny, E Falkensammer, B Ugucchioni, M Georgsson, G Baroni, C Dierich, MP Lifson, JD Steinman, RM Uberla, K Racz, P Ignatius, R AF Stahl-Hennig, Christiane Eisenblatter, Martin Franz, Monika Stoiber, Heribert Tenner-Racz, Klara Suh, You-Suk Jasny, Edith Falkensammer, Barbara Ugucchioni, Mariagrazia Georgsson, Gudmundur Baroni, Carlo Dierich, Manfred P. Lifson, Jeffrey D. Steinman, Ralph M. Uberla, Klaus Racz, Paul Ignatius, Ralf TI A single vaccination with attenuated SIVmac 239 via the tonsillar route confers partial protection against challenge with SIVmac 251 at a distant mucosal site, the rectum SO FRONTIERS IN BIOSCIENCE LA English DT Article DE rhesus macaques; SIV Delta nef; tonsillar immunization; rectal infection; protection; review ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL DEPLETION; RHESUS MACAQUES; DENDRITIC CELLS; IMMUNE-SYSTEM; IMMUNOLOGICAL SYSTEM; LIVE; INFECTION; REPLICATION; RESPONSES AB Elucidating the mechanisms that protect monkeys previously immunized with attenuated SIV ( SIVDeltanef) against challenge infection with pathogenic virus may reveal new strategies for the development of an effective HIV vaccine. Here we show that a single atraumatic application of SIVDeltanef to the tonsils of four rhesus macaques conferred protection against SIVmac251 applied intrarectally 26 weeks later. While this protection was not complete, i.e., challenge virus could be isolated from all immunized animals, it was reflected by significantly lower viral loads in the blood ( weeks 2-16 after challenge, p < 0.01) and considerably lower loads in lymphoid organs, and more stable peripheral CD4 counts in a proportion of the immunized animals as compared to four non-immunized, SIVmac251-infected control monkeys. SIV-specific humoral as well as systemic and mucosal T cell responses were detected in the immunized animals, but there was no correlation between their magnitude of expression and the level of protection. Analyses of leukocyte subsets in these animals at necropsy ( 24 weeks after challenge) did not reveal a significantly enhanced proportion of gamma/delta T cells in the tissues of protected monkeys. Therefore, tonsillar application of attenuated SIV induces protection in some animals against a superinfection with wild-type SIV distant at a distant mucosal site. C1 Charite Univ Med Berlin, Dept Med Microbiol & Infect Immunol, D-12203 Berlin, Germany. German Primate Ctr, D-37077 Gottingen, Germany. Med Univ Innsbruck, Dept Hyg Microbiol & Social Med, A-6020 Innsbruck, Austria. Bernhard Nocht Inst Trop Med, Dept Pathol, D-20359 Hamburg, Germany. Univ Iceland, Inst Expt Pathol, IS-101 Reykjavik, Iceland. Inst Res Biomed, Bellinzona, Switzerland. Univ Roma La Sapienza, Policlin Umberto I, Dept Expt Med & Pathol, I-00161 Rome, Italy. NCI, Retroviral Pathogenesis Lab, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. Rockefeller Univ, Lab Cellular Physiol & Immunol, New York, NY 10021 USA. Ruhr Univ Bochum, Dept Mol & Med Virol, D-44780 Bochum, Germany. RP Ignatius, R (reprint author), Charite Univ Med Berlin, Dept Med Microbiol & Infect Immunol, Campus Benjamin Franklin,Hindenburgdamm 27, D-12203 Berlin, Germany. EM ralf.ignatius@charite.de RI Uberla, Klaus/C-5676-2008; Steinman, Ralph/F-7729-2012 FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [AI40874] NR 42 TC 12 Z9 12 U1 0 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2007 VL 12 BP 2107 EP 2123 DI 10.2741/2215 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 129QS UT WOS:000243745000172 PM 17127448 ER PT J AU Tjoa, ML Levine, RJ Karumanchi, SA AF Tjoa, May Lee Levine, Richard J. Karumanchi, S. Ananth TI Angiogenic factors and preeclampsia SO FRONTIERS IN BIOSCIENCE LA English DT Article DE preeclampsia; angiogenic growth factors; soluble Flt1; soluble endoglin; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; BETA RECEPTOR SYSTEM; TYROSINE KINASE-1; SPIRAL ARTERIES; PLACENTAL BED; DIFFERENTIAL EXPRESSION; HUMAN CYTOTROPHOBLASTS; TROPHOBLAST MIGRATION; ENDOVASCULAR INVASION; MOLECULAR EVIDENCE AB Preeclampsia is a major cause of maternal and neonatal morbidity and mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, hypertension and proteinuria, may be due to an excess of circulating anti-angiogenic growth factors, most notably soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng). sFlt1 is an endogenous protein that is produced by the placenta. sFlt1 is able to bind to the angiogenic growth factors vascular endothelial growth factor and placental growth factor, thereby neutralizing their functions. High serum concentrations of sFlt1 and low concentrations of free vascular endothelial growth factor and free placental growth factor have been observed during and prior to clinical manifestation of preeclampsia. More recently, serum levels of sEng were also shown to be significantly elevated in preeclamptic women and levels of sEng correlated strongly with disease severity. Therefore, measurement of sFlt1 and sEng in the maternal circulation may be a useful diagnostic and screening tool for preeclampsia. The availability of such a test to predict preeclampsia would have significant impact on current obstetrical care and may help reduce preeclampsia-induced morbidity and mortality. This review will focus on the role of angiogenic factors in normal and abnormal placental development and indicate how measurement of circulating angiogenic factors may help identify women at risk of preeclampsia. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave,RW 663, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL079594]; NIDDK NIH HHS [R01 DK 065997] NR 62 TC 45 Z9 45 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2007 VL 12 BP 2395 EP 2402 DI 10.2741/2241 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 129QS UT WOS:000243745000198 PM 17127249 ER PT J AU England, L Zhang, J AF England, Lucinda Zhang, Jun TI Smoking and risk of preeclampsia: a systematic review SO FRONTIERS IN BIOSCIENCE LA English DT Review DE pregnancy; preeclampsia; smoking; review ID INTRAUTERINE GROWTH RESTRICTION; OBSTRUCTIVE PULMONARY-DISEASE; NITRIC-OXIDE SYNTHASE; CIRCULATING ANGIOGENIC FACTORS; PREGNANCY-INDUCED HYPERTENSION; MONOZYGOTIC TWINS DISCORDANT; FETAL-PLACENTAL CIRCULATION; EARLY-ONSET PREECLAMPSIA; POPULATION-BASED COHORT; CELL-ADHESION MOLECULE AB Cigarette smoking adversely affects every organ system. Paradoxically, smoking during pregnancy has been associated with a reduced risk of preeclampsia. We reviewed previous epidemiologic and clinical studies on the association between smoking and preeclampsia from 1959 to March, 2006. A total of 48 epidemiologic studies were identified. Overall, smoking during pregnancy reduces the risk of preeclampsia by up to 50% with a dose-response pattern. A protective effect was consistently found in both nulliparas and multiparas, singleton and multifetal pregnancies, and for mild and severe preeclampsia. Evidence on whether quitting smoking before or in early pregnancy reduces the risk remains inconclusive. To understand possible biologic mechanism(s) of the protective effect, we reviewed literature on potential pathophysiology of smoking and its effects on placenta, cardiovascular and immune systems. Although current literature does not lend clear evidence to support a particular mechanism for the protective effect of smoking, smoking might have effects on angiogenic factors, endothelial function and the immune system which act to lower risk of preeclampsia. More epidemiologic studies with biochemically confirmed smoking status and laboratory studies with a focus on promising pathways are warranted to further clarify this puzzling relationship. Understanding the underlying mechanisms through which smoking reduces preeclampsia risk may enhance our understanding of the pathogenesis of this disorder and contribute to the development of prevention strategies. C1 NICHHD, Epidemiol Branch, NIH, Div Epidemiol Stat & Prevent Res,Dept Hlth & Huma, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Dept Hlth & Human Serv, Atlanta, GA USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Div Epidemiol Stat & Prevent Res,Dept Hlth & Huma, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM zhangj@exchange.nih.gov FU Intramural NIH HHS NR 159 TC 87 Z9 88 U1 2 U2 13 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2007 VL 12 BP 2471 EP 2483 DI 10.2741/2248 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 129QS UT WOS:000243745000205 PM 17127256 ER PT S AU Pozsgay, V Kubler-Kielb, J AF Pozsgay, Vince Kubler-Kielb, Joanna BE Demchenko, AV TI Synthesis of Carbohydrate Antigens Related to Shigella dysenteriae Type 1 and of Their Protein Conjugates SO FRONTIERS IN MODERN CARBOHYDRATE CHEMISTRY SE ACS SYMPOSIUM SERIES LA English DT Proceedings Paper CT Symposium on Frontiers in Modern Carbohydrate Chemistry held at the 229th ACS National Meeting CY MAR 13-17, 2005 CL San Diego, CA SP Ame Chem Soc, Div Agr & Food Chem ID VACCINES; SONNEI AB Shigella dysenteriae type I is a major cause of dysentery worldwide but there is no licensed vaccine against these bacteria. The lipopolysaccharide of S. dysenteriae type 1 is both an essssential virulence factor and a protective antigen. We describe synthesis of oligosaccharides corresponding to the repeating subunits of the O-specific polysaccharide followed by an efficient method for their covalent binding to the protein carrier, in order to obtain a well defined synthetic glycoconjugate vaccine. C1 [Pozsgay, Vince; Kubler-Kielb, Joanna] NICHHD, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, NIH, 6 Ctr Dr,MSC 2720, Bethesda, MD 20892 USA. NR 13 TC 3 Z9 3 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3970-8 J9 ACS SYM SER PY 2007 VL 960 BP 238 EP 252 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA BKS03 UT WOS:000269052400014 ER PT S AU Svarovsky, SA Barchi, JJ AF Svarovsky, Sergei A. Barchi, Joseph J., Jr. BE Demchenko, AV TI De Novo Synthesis of Biofunctional Carbohydrate-Encapsulated Quantum Dots SO FRONTIERS IN MODERN CARBOHYDRATE CHEMISTRY SE ACS SYMPOSIUM SERIES LA English DT Proceedings Paper CT Symposium on Frontiers in Modern Carbohydrate Chemistry held at the 229th ACS National Meeting CY MAR 13-17, 2005 CL San Diego, CA SP Ame Chem Soc, Div Agr & Food Chem ID IN-VIVO; GOLD GLYCONANOPARTICLES; BIOLOGICAL MOLECULES; TUMOR-ANTIGEN; HUMAN BREAST; T-ANTIGEN; CELLS; NANOPARTICLES; NANOCRYSTALS; ENDOTHELIUM AB Semiconductor nanocrystals, also called quantum dots (QDs) are particles that exhibit unique size- and composition-dependent optical properties. Several recent reports have described the synthesis of QDs coated with a variety of biomolecules for cellular imaging applications. We have prepared QDs coated with the tumor-associated carbohydrate antigen (TACA) disaccharide Gal beta 1-3GalNAc alpha- (Thomsen Friedenreich antigen) O-conjugated to various linkers and studied their photoluminescent and binding properties. The de novo synthesis of highly stable, luminescent and functional quantum dots was achieved by the use of a "hybrid" system containing small percentages of different surface passivating agents along with an appropriate neoglycoconjugate. The glycan-coated quantum dots were prepared in a simple one-pot procedure that is amenable to various other saccharides. Initial studies with thiolacetic acid as a co-capping agent produced highly luminescent particles with functional carbohydrate units but the negative charge was undesirable for important applications such as cellular bioimaging. Replacement of this small organic acid with a short modified polyethylene glycol segment yielded quantum dots with very similar properties but C1 [Svarovsky, Sergei A.; Barchi, Joseph J., Jr.] NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. RP Svarovsky, SA (reprint author), NCI, Ctr Canc Res, Med Chem Lab, 376 Boyles St,POB B, Frederick, MD 21702 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 42 TC 8 Z9 8 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3970-8 J9 ACS SYM SER PY 2007 VL 960 BP 375 EP 392 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA BKS03 UT WOS:000269052400020 ER PT J AU Wilting, A Buckley-Beason, VA Feldhaar, H Gadau, J O'Brien, SJ Linsenmair, KE AF Wilting, Andreas Buckley-Beason, Valerie A. Feldhaar, Heike Gadau, Juergen O'Brien, Stephen J. Linsenmair, K. Eduard TI Clouded leopard phylogeny revisited: support for species recognition and population division between Borneo and Sumatra SO FRONTIERS IN ZOOLOGY LA English DT Article AB Background: The clouded leopard (Neofelis nebulosa) is one of the least known cat species and depletion of their forested habitats puts it under heavy pressure. Recently reclassification of Bornean clouded leopards (N. nebulosa diardi) to species level (N. diardi) was suggested based on molecular and morphological evidence. Since the genetic results were based solely on three Bornean samples we re-evaluated this partition using additional samples of Bornean clouded leopards (N = 7) and we were also able to include specimens from Sumatra (N = 3), which were lacking in previous analysis. Results: We found strong support for the distinction between N. nebulosa and N. diardi based on three fragments of mtDNA (900 bp) and 18 microsatellites. Forty-one fixed mitochondrial nucleotide differences and non-overlapping allele sizes in 8 of 18 microsatellite loci distinguished N. nebulosa and N. diardi. This is equivalent to the genetic divergence among recognized species in the genus Panthera. Sumatran clouded leopards clustered with specimens from Borneo, suggesting that Sumatran individuals also belong to N. diardi. Additionally, a significant population subdivision was apparent among N. diardi from Sumatra and Borneo based on mtDNA and microsatellite data. Conclusion: Referring to their origin on two Sunda Islands we propose to give N. diardi the common name "Sundaland clouded leopard". The reduced gene flow between Borneo and Sumatra might suggest the recognition of two subspecies of N. diardi. Based on this reclassification of clouded leopards not only species, but also the populations on Borneo and Sumatra should be managed separately and a higher priority should be placed to protect the different populations from extinction. C1 [Wilting, Andreas; Linsenmair, K. Eduard] Univ Wurzburg, Bioctr, Dept Anim Ecol & Trop Biol, D-97074 Wurzburg, Germany. [Buckley-Beason, Valerie A.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Feldhaar, Heike] Univ Wurzburg, Bioctr, Dept Behav Physiol & Sociobiol, D-97074 Wurzburg, Germany. [Gadau, Juergen] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. RP Wilting, A (reprint author), Univ Wurzburg, Bioctr, Dept Anim Ecol & Trop Biol, D-97074 Wurzburg, Germany. EM a.wilting@gmx.de; vbuckley@gmu.edu; feldhaar@biozentrum.uni-wuerzburg.de; juergen.gadau@asu.edu; obrien@mail.ncifcrf.gov; ke_lins@biozentrum.uni-wuerzburg.de OI Feldhaar, Heike/0000-0001-6797-5126 FU Point Defiance Zoo and Aquarium and Duisburg Zoo FX We thank D. Hesse for comments on earlier drafts of this manuscript. Special thanks also go to all institutions listed in Table 1 that supplied the biological specimens this work is based upon. We would also like to thank CITES agencies for issuing the specific permits to the University of Wurzburg and the National Cancer Institute. Point Defiance Zoo and Aquarium and Duisburg Zoo provided financial support for data collection. NR 67 TC 24 Z9 26 U1 4 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-9994 J9 FRONT ZOOL JI Front. Zool. PY 2007 VL 4 AR 15 DI 10.1186/1742-9994-4-15 PG 10 WC Zoology SC Zoology GA V35OL UT WOS:000209158400015 PM 17535420 ER PT S AU Pop, M Sermesant, M Chung, D Liu, G McVeigh, ER Crystal, E Wright, GA AF Pop, Mihaela Sermesant, Maxime Chung, Desmond Liu, Garry McVeigh, Elliot R. Crystal, Eugene Wright, Graham A. BE Sachse, FB Seemann, G TI An experimental framework to validate 3D models of cardiac electrophysiology via optical imaging and MRI SO FUNCTIONAL IMAGING AND MODELING OF THE HEART, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 4th International Conference on Functional Imaging and Modeling of the Heart CY JUN 07-09, 2007 CL Univ Utah, Salt Lake City, UT SP IEEE Engn Med & Biol Soc HO Univ Utah DE computer modelling; electrophysiology; optical imaging; MRI ID ELECTROMECHANICAL MODEL; HEART; PROPAGATION; PATTERNS AB Our aim is to develop a framework to validate 3-D computer models of cardiac electrophysiology using measurements of action potential obtained via optical imaging (based on voltage-sensitive fluorescence), and heart anatomy and fiber directions which are obtained from magnetic resonance imaging (MRI). In this paper we present preliminary results of this novel framework using a healthy porcine heart ex vivo model and the Aliev & Panfilov mathematical model. This experimental setup will facilitate the testing, validation and adjustment of computational models prior to their integration into clinical applications. C1 [Pop, Mihaela; Chung, Desmond; Liu, Garry; Wright, Graham A.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Biophys, Toronto, ON, Canada. [Sermesant, Maxime] INRIA Sophia Antipolis, ASCLEPIOS project, Sophia Antipolis, France. [Sermesant, Maxime] Kings Coll London, Div Imaging Sci, London, England. [McVeigh, Elliot R.] Natl Inst Hlth, Natl Heart Lung & Blood Inst, Lab Cardiac Energet, Bethesda, MD USA. [Crystal, Eugene] Sunnybrook Hlth Sci Ctr, Arrhythmia Serv, Toronto, ON, Canada. RP Pop, M (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Biophys, Toronto, ON, Canada. EM mpop@swri.ca OI Sermesant, Maxime/0000-0002-6256-8350 FU Ontario Research and Development Challenge Fund; Canadian Foundation for Innovation; Ontario Innovation Trust FX The authors would like to thank Dr. J. M. Rogers (University of Alabama, Birmingham, USA) for valuable discussions regarding the optical technique, Dr. Patrick Helm (University of Virginia, USA) for help with implementing the diffusion-weighted sequence on our scanner, Mr. A. Kim and Mr. K. Anderson for technical assistance with the optical set-up and to the veterinary technicians at Sunnybrook for help with the animal studies. This study was supported by funding from the Ontario Research and Development Challenge Fund, the Canadian Foundation for Innovation, and the Ontario Innovation Trust. Ms. Mihaela Pop is supported by a PhD scholarship from the Heart and Stroke Foundation of Canada. NR 19 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-72906-8 J9 LECT NOTES COMPUT SC PY 2007 VL 4466 BP 100 EP + PG 3 WC Cardiac & Cardiovascular Systems; Computer Science, Theory & Methods; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI37 UT WOS:000247326500011 ER PT S AU Peyrat, JM Sermesant, M Pennec, X Delingette, H Xu, CY McVeigh, E Ayache, N AF Peyrat, Jean-Marc Sermesant, Maxime Pennec, Xavier Delingette, Herve Xu, Chenyang McVeigh, Elliot Ayache, Nicholas BE Sachse, FB Seemann, G TI Statistical comparison of cardiac fibre architectures SO FUNCTIONAL IMAGING AND MODELING OF THE HEART, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 4th International Conference on Functional Imaging and Modeling of the Heart CY JUN 07-09, 2007 CL Univ Utah, Salt Lake City, UT SP IEEE Engn Med & Biol Soc HO Univ Utah ID HEART; SIMULATION; MODEL; WALL AB In this paper, a statistical atlas of DT-MRIs based on a population of nine ex vivo normal canine hearts is compared with a human cardiac DT-MRI and with a synthetic model of the fibre orientation. The aim of this paper is to perform a statistical inter-species comparison of the cardiac fibre architecture and to assess the quality of a synthetic description of the fibre orientation. We present the framework to build a statistical atlas of cardiac DT-MRIs providing a mean and a covariance matrix of diffusion tensors at each voxel of an average geometry. The comparison of human and synthetic data with this atlas involves the non-rigid registration into the average atlas geometry where voxel to voxel comparison can be performed. For each eigenvector of the diffusion tensors, we compute the angular difference with the average atlas and its Mahalanobis distance to the canine population. The results show a better consistence of the fibre orientation than the laminar sheet orientation between the human and the canine heart, while the homogeneous synthetic model appears to be too simple compared to the complexity of real cardiac geometry and fibre architecture. C1 [Peyrat, Jean-Marc; Sermesant, Maxime; Pennec, Xavier; Delingette, Herve; Ayache, Nicholas] INRIA, Asclepios Res Project, Sophia Antipolis, France. [Sermesant, Maxime] Kings Coll London, Guys Hosp, Cardiac MR Res Grp, London WC2R 2LS, England. [Xu, Chenyang] Siemens Corp Res, Princeton, NJ USA. [McVeigh, Elliot] NIH, Natl Heart Lung & Blood Inst, Cardiac Energet Lab, Bethesda, MD USA. RP Peyrat, JM (reprint author), INRIA, Asclepios Res Project, Sophia Antipolis, France. EM jean-marc.peyrat@sophia.inria.fr RI Pennec, Xavier/L-2537-2013; OI Pennec, Xavier/0000-0002-6617-7664; Sermesant, Maxime/0000-0002-6256-8350 FU Siemens Corporate Research, Princeton, NJ; Intramural Research Program of the National Heart Lung and Blood Institute [Z01-HL4004609] FX This research was funded by Siemens Corporate Research, Princeton, NJ. Acquisition of the DT-MRIs data was funded by the Intramural Research Program of the National Heart Lung and Blood Institute (E.R. McVeigh Z01-HL4004609). We thank Drs. Patrick A. Helm and Raimond L. Winslow at the Center for Cardiovascular Bioinformatics and Modeling for provision of data, P. Fillard and N. Toussaint for provision of diffusion tensors and fibre tracking computation and visualization tools. NR 24 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-72906-8 J9 LECT NOTES COMPUT SC PY 2007 VL 4466 BP 413 EP + PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Theory & Methods; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BGI37 UT WOS:000247326500042 ER PT S AU Hikosaka, O AF Hikosaka, O. BE Tepper, JM Abercrombie, ED Bolam, JP TI GABAergic output of the basal ganglia SO GABA AND THE BASAL GANGLIA: FROM MOLECULES TO SYSTEMS SE Progress in Brain Research LA English DT Review DE substantia nigra pars reticulata; internal segment of globus pallidus; caudate nucleus; putamen; selection of behavior; saccadic eye movement; superior colliculus; memory-guided behavior; sequential procedure; reward; involuntary movement ID NIGRA PARS RETICULATA; SACCADIC EYE-MOVEMENTS; MESENCEPHALIC-LOCOMOTOR-REGION; MONKEY CAUDATE NEURONS; PRIMATE SUPERIOR COLLICULUS; GABA-RELATED SUBSTANCES; AMINOBUTYRIC ACID GABA; BRAIN-STEM INTEGRATION; PARKINSONS-DISEASE; GLOBUS-PALLIDUS AB Using GABAergic outputs from the SNr or GP(i), the basal ganglia exert inhibitory control over several motor areas in the brainstem which in turn control the central pattern generators for the basic motor repertoire including eye-head orientation, locomotion, mouth movements, and vocalization. These movements are by default kept suppressed by tonic rapid firing of SNr/GP(i) neurons, but can be released by a selective removal of the tonic inhibition. Derangement of the SNr/GP(i) outputs leads to either an inability to initiate movements (akinesia) or an inability to suppress movements (involuntary movements). Although the spatio-temporal patterns of individual movements are largely innate and fixed, it is essential for survival to select appropriate movements and arrange them in an appropriate order depending on the context, and this is what the basal ganglia presumably do. To achieve such a goal, however, the basal ganglia need to be trained to optimize their outputs with the aid of cortical inputs carrying sensorimotor and cognitive information and dopaminergic inputs carrying reward-related information. The basal ganglia output to the thalamus, which is particularly developed in primates, provides the basal ganglia with an advanced ability to organize behavior by including the motor skill mechanisms in which new movement patterns can be created by practice. To summarize, an essential function of the basal ganglia is to select, sort, and integrate innate movements and learned movements, together with cognitive and emotional mental operations, to achieve purposeful behaviors. Intricate hand-finger movements do not occur in isolation; they are always associated with appropriate motor sets, such as eye-head orientation and posture. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. 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 198 TC 70 Z9 71 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-52184-2 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2007 VL 160 BP 209 EP 226 DI 10.1016/S0079-6123(06)60012-5 PG 18 WC Neurosciences SC Neurosciences & Neurology GA BGN57 UT WOS:000248622200012 PM 17499116 ER PT J AU Shiffman, ML Ghany, MG Morgan, TR Wright, EC Everson, GT Lindsay, KL Lok, ASF Bonkovsky, HL Di Bisceglie, AM Lee, WM Dienstag, JL Gretch, DR AF Shiffman, Mitchell L. Ghany, Marc G. Morgan, Timothy R. Wright, Elizabeth C. Everson, Gregory T. Lindsay, Karen L. Lok, Anna S. F. Bonkovsky, Herbert L. Di Bisceglie, Adrian M. Lee, William M. Dienstag, Jules L. Gretch, David R. CA HALT-C Trial Grp TI Impact of reducing peginterferon alfa-2a and ribavirin dose during Retreatment in patients with chronic hepatitis C SO GASTROENTEROLOGY LA English DT Article ID HCV-INFECTED PATIENTS; PLUS RIBAVIRIN; COMBINATION THERAPY; INITIAL TREATMENT; PEGYLATED INTERFERON; GENOTYPE-1 PATIENTS; DOUBLE-BLIND; TRIAL; MAINTENANCE; ANEMIA AB Background & Aims: Reducing the dose of peginterferon and/or ribavirin to < 80% when treating chronic hepatitis C virus has been associated with a reduction in sustained virologic response (SVR). However, prior studies did not assess the impact of reducing the dose of peginterferon independent of ribavirin or differentiate between dose reduction or interrupting or prematurely discontinuing treatment. Methods: Nine hundred thirty-six patients with chronic hepatitis C genotype 1, advanced fibrosis, or cirrhosis (Ishak 3-6) and prior nonresponse to standard interferon +/- ribavirin were retreated with peginterferon alfa-2a (180 mu g/wk) and ribavirin (1000-1200 mg/day) during the lead-in phase of the HALT-C trial. The percentage of each medication actually taken during treatment was calculated. Results: Reducing the total cumulative dose of peginterferon received during the first 20 weeks of treatment from full dose ( >= 98%) to <= 60% reduced week 20 virologic response (W20 VR) from 35% to 12% and SVR from 17% to 5%. Reducing the dose of ribavirin from full dose ( >= 98%) to <= 60% did not affect either W20 VR or SVR as long as ribavirin dosing was not interrupted for more than 7 consecutive days. Prematurely discontinuing ribavirin, even at full-dose peginterfero n, reduced W20 VR to <= 19% and SVR to <= 4%. Conclusions: Reducing the peginterferon dose during the first 20 weeks of treatment reduced viral clearance and SVR. In contrast, reducing ribavirin did not affect either W20 VR or SVR as long as patients remained on full-dose peginterferon. Discontinuing ribavirin prematurely was associated with a marked decline in both VR and SVR. C1 Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA 23298 USA. NIDDK, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA 92717 USA. VA Long Beach Healthcare Syst, Serv Gastroenterol, Long Beach, CA USA. New England Res Inst, Watertown, MA 02172 USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90089 USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ Connecticut, Ctr Hlth, Dept Med, Storrs, CT 06269 USA. Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Storrs, CT 06269 USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Storrs, CT 06269 USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75230 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Shiffman, ML (reprint author), Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Box 980341, Richmond, VA 23298 USA. EM mshiffma@vcu.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 NR 23 TC 138 Z9 146 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2007 VL 132 IS 1 BP 103 EP 112 DI 10.1053/j.gastro.2006.11.011 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 131BR UT WOS:000243843500017 PM 17241864 ER PT J AU Luciani, MG Campregher, C Fortune, JM Kunkel, TA Gasche, C AF Luciani, M. Gloria Campregher, Christoph Fortune, John M. Kunkel, Thomas A. Gasche, Christoph TI 5-ASA affects cell cycle progression in colorectal cells by reversibly activating a replication checkpoint SO GASTROENTEROLOGY LA English DT Article ID COLON-CANCER CELLS; INFLAMMATORY-BOWEL-DISEASE; S-PHASE CHECKPOINT; ULCERATIVE-COLITIS; DNA-REPLICATION; 5-AMINOSALICYLIC ACID; MITOTIC CATASTROPHE; GROWTH-INHIBITION; TUMOR-SUPPRESSOR; P53 MUTATION AB Background & Aims: individuals with inflammatory bowel disease are at risk of developing colorectal cancer (CRC). Epidemiologic, animal, and laboratory studies suggest that 5-amino-salicylic acid (5-ASA) protects from the development of CRC by altering cell cycle progression and by inducing apoptosis. Our previous results indicate that 5-ASA improves replication fidelity in colorectal cells, an effect that is active in reducing mutations. In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. Methods: CRC cells with different genetic backgrounds such as HT29, HCT116, HCT116(p53-/-), HCT116+chr3, and LoVo were treated with 5-ASA for 2-96 hours. Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. Results: We found that 5-ASA at concentrations between 10 and 40 mmol/L affects cell cycle progression by inducing cells to accumulate in the S phase. This effect was independent of the hMLH1, hMSH2, and p53 status because it was observed to a similar extent in all cell lines under investigation. Moreover, wash-out experiments demonstrated reversibility within 48 hours. Although p53 did not have a causative role, p53 Ser15 was strongly phosphorylated. Proteins involved in the ATM-and-Rad3-related kinase (ATR)dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. -Conclusions: Our data demonstrate that S-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance C1 MUW Wien, Dept Internal Med 4, Div Gastroenterol & Hepatol, A-1090 Vienna, Austria. Natl Inst Environm Hlth Sci, Lab Mol Genet, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. RP Gasche, C (reprint author), MUW Wien, Dept Internal Med 4, Div Gastroenterol & Hepatol, KIM4,Wahringer Gurtel 18, A-1090 Vienna, Austria. EM christoph.gasche@meduniwien.ac.at RI Gasche, Christoph/A-5139-2013 FU Austrian Science Fund FWF [P 18270]; Intramural NIH HHS NR 65 TC 49 Z9 50 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2007 VL 132 IS 1 BP 221 EP 235 DI 10.1053/j.gastro.2006.10.016 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 131BR UT WOS:000243843500027 PM 17241873 ER PT J AU Park, JM Intine, RV Maraia, RJ AF Park, Jung-Min Intine, Robert V. Maraia, Richard J. TI Mouse and human La proteins differ in kinase substrate activity and activation mechanism for tRNA processing SO GENE EXPRESSION LA English DT Article DE tRNA processing; ade6-704; tRNA-mediated suppression; CK2; protein kinase A; La motif; Mdm2; C5 RNA ID RIBOSOME ENTRY SITE; POLYMERASE-III TRANSCRIPTS; PRECURSOR TRANSFER-RNAS; SERINE TRANSFER-RNA; SS-B AUTOANTIGEN; LUPUS ANTIGEN-LA; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; NASCENT RNA; SMALL RIBONUCLEOPROTEINS AB The La protein interacts with a variety of small RNAs as well as certain growth-associated mRNAs such as Mdm2 mRNA. Human La (hLa) phosphoprotein is so highly conserved that it can replace the tRNA processing function of the fission yeast La protein in vivo. We used this system, which is based on tRNA-mediated suppression (TMS) of ade6-704 in S. pombe, to compare the activities of mouse and human La proteins. Prior studies indicate that hLa is activated by phosphorylation of serine-366 by protein kinase CK2, neutralizing a negative effect of a short basic motif (SBM). First, we report the sequence mapping of the UGA stop codon that requires suppressor tRNA for TMS, to an unexpected site in S. pombe ade6-704. Next, we show that, unlike hLa, native mLa is unexpectedly inactive for TMS, although its intrinsic activity is revealed by deletion of its SBM. We then show that mLa is not phosphorylated by CK2, accounting for the mechanistic difference between mLa and hLa. We found a PKA/PKG target sequence in mLa (S 199) that is not present in hLa, and show that PKA/PKG efficiently phosphorylates mLa S199 in vitro. A noteworthy conclusion that comes from this work is that this fission yeast system can be used to gain insight into differences in control mechanisms used by La proteins of different mammalian species. Finally, RNA binding assays indicate that while mutation of mLa S 199 has little effect on pre-tRNA binding, it substantially decreases binding to a probe derived from Mdm2 mRNA. In closing, we note that species-specific signaling through La may be relevant to the La-dependent Mdm2 pathways of p53 metabolism and cancer progression in mice and humans. C1 [Park, Jung-Min; Intine, Robert V.; Maraia, Richard J.] NICHHD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Maraia, RJ (reprint author), NICHHD, Intramural Res Program, NIH, 31 Ctr Dr,Room 2A25, Bethesda, MD 20892 USA. EM maraiar@mail.nih.gov FU Intramural NIH HHS NR 57 TC 6 Z9 6 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 1052-2166 EI 1555-3884 J9 GENE EXPRESSION JI Gene Expr. PY 2007 VL 14 IS 2 BP 71 EP 81 DI 10.3727/105221607783417619 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 255OX UT WOS:000252668400002 PM 18257391 ER PT J AU Kaur, S Abu-Abab, MS Singla, S Yeo, SY Ramchandran, R AF Kaur, Sukhbir Abu-Abab, Mones S. Singla, Shobhit Yeo, Sang-Yeob Ramchandran, Ramani TI Expression pattern for unc5b, an axon guidance gene in embryonic zebrafish development SO GENE EXPRESSION LA English DT Article DE unc5b; robo4; hindbrain; axon guidance; zebrafish; staining ID ANGIOGENESIS; RECEPTOR AB Branching processes such as nerves and vessels share molecular mechanisms of path determination. Our study focuses on unc5b, a member of the unc5 axon guidance gene family. Here, we have cloned the full-length zebrafish ortholog of unc5b, mapped its chromosome location in the zebrafish genome, and compared its expression patterns to robo4, another axon guidance family member. In situ show that unc5b is expressed predominantly in sensory structures such as the eye, ear, and brain. Both unc5b and robo4 show robust expression in all three compartments of the embryonic brain, namely forebrain, midbrain, and hindbrain. In particular, the hindbrain rhombomere expression displays interesting patterns in that robo4 is expressed in medial rhombomere cell clusters when compared to unc5b expressed in lateral rhombomere clusters. A similar medial-lateral theme is observed in other neural structures such as the neural tube. Our expression analysis provides a starting point for studying the role of axon guidance genes in embryonic hindbrain patterning. C1 Med Coll Wisconsin, Dept Pediat, CRI Dev Biol, Translat & Biomed Res Ctr,Dev Vasc Biol Program, Milwaukee, WI 53226 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY USA. NICHD, Mol Genet Lab, Unit Vertebrate Neural Dev, NIH, Bethesda, MD USA. RP Ramchandran, R (reprint author), Med Coll Wisconsin, Dept Pediat, CRI Dev Biol, Translat & Biomed Res Ctr,Dev Vasc Biol Program, 8701 Watertown Plank Rd,C3420,POB 26509, Milwaukee, WI 53226 USA. EM rramchan@mcw.edu FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [K22 CA095325, K22 CA095325-01, K22 CA095325-02] NR 15 TC 5 Z9 5 U1 1 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 2007 VL 13 IS 6 BP 321 EP 327 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 198BU UT WOS:000248602800003 PM 17708418 ER PT J AU Aihara, Y Yasuoka, A Yoshida, Y Ohmoto, M Shimizu-Ibuka, A Misaka, T Furutani-Seiki, M Matsumoto, I Abe, K AF Aihara, Yoshiko Yasuoka, Akihito Yoshida, Yuki Ohmoto, Makoto Shimizu-Ibuka, Akiko Misaka, Takumi Furutani-Seiki, Makoto Matsumoto, Ichiro Abe, Keiko TI Transgenic labeling of taste receptor cells in model fish under the control of the 5 '-upstream region of medaka phospholipase C-beta 2 gene SO GENE EXPRESSION PATTERNS LA English DT Article DE in vivo labeling; taste bud; taste receptor cell; medaka; zebrafish; phospholipase C-beta 2; transgene; promoter ID ORYZIAS-LATIPES; BITTER TASTE; NEURAL CREST; BUD CELLS; EXPRESSION; ZEBRAFISH; NEUROGENESIS; PLC-BETA-2; EPITHELIUM; HINDBRAIN AB Vertebrate taste receptor cells express signaling molecules such as taste receptors and effectors to convert taste stimuli to inner cellular signals. Phospholipase C-beta 2 (PLC-beta 2) is an effector enzyme that is necessary to transduce taste signals in the mouse. It was shown that a subset of the plc-beta 2 expressing cells also express taste receptor molecules, T1Rs or T2Rs, in mammals and fish. To label plc-beta 2 expressing cells in the model fish species, we constructed a transgene by linking the 5'-upstream region of the medaka plc-beta 2 gene to a green fluorescent protein (GFP) gene. The resulting transgenic medaka exhibited GFP signals in taste buds of the lips and the pharyngeal region. Detailed observation revealed that the GFP signals were in a subpopulation of taste bud cells, and co-localized with the transcript of endogenous plc-beta 2 gene. Zebrafish introduced with the same transgene showed GFP signals in a subpopulation of taste bud cells of the lips and the pharyngeal region as in the case of medaka. This is the first report of successful labeling of taste receptor cells in two model fish species under the control of the plc-beta 2 promoter. This promoter will be a useful genetic tool to study the vertebrate taste system in general. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Bunkyo Ku, Tokyo 1138657, Japan. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Tokyo Univ Agr, Fac Appl Biol Sci, Dept Nutr Sci, Setagaya Ku, Tokyo 1568502, Japan. Japan Sci & Technol Agcy, Kondoh Res Team, Solut Oriented Res Sci & Technol Program, Sakyo Ku, Kyoto 6068305, Japan. RP Abe, K (reprint author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan. EM aka7308@mail.ecc.u-tokyo.ac.jp OI SHIMIZU-IBUKA, Akiko/0000-0002-5310-9216 NR 35 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD JAN PY 2007 VL 7 IS 1-2 BP 149 EP 157 DI 10.1016/j.modgep.2006.06.004 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 115MT UT WOS:000242739100020 PM 16920036 ER PT J AU Habermann, JK Paulsen, U Roblick, UJ Upender, MB McShane, LM Korn, EL Wangsa, D Kruger, S Duchrow, M Bruch, HP Auer, G Ried, T AF Habermann, Jens K. Paulsen, Ulrike Roblick, Uwe J. Upender, Madhvi B. McShane, Lisa M. Korn, Edward L. Wangsa, Danny Krueger, Stefan Duchrow, Michael Bruch, Hans-Peter Auer, Gert Ried, Thomas TI Stage-specific alterations of the genorne, transcriptorne, and proteome during colorectal carcinogenesis SO GENES CHROMOSOMES & CANCER LA English DT Article ID GENE-EXPRESSION PROFILES; COLON-CANCER; CELLULAR TRANSCRIPTOME; CARCINOMA; INSTABILITY; ANEUPLOIDY; IDENTIFICATION; AMPLIFICATION; PROGRESSION; MICROARRAYS AB To identify sequential alterations of the genome, transcriptome, and proteome during colorectal cancer progression, we have analyzed tissue samples from 36 patients, including the complete mucosa-adenoma-carcinoma sequence from 8 patients. Comparative genomic hybridization (CGH) revealed patterns of stage specific, recurrent genomic imbalances. Gene expression analysis on 9K cDNA arrays identified 58 genes differentially expressed between normal mucosa and adenoma, 116 genes between adenoma and carcinoma, and 158 genes between primary carcinoma and liver metastasis (P < 0.001), Parallel analysis of our samples by CGH and expression profiling revealed a direct correlation of chromosomal copy number changes with chromosome-specific average gene expression levels. Protein expression was analyzed by two-dimensional gel electrophoresis and subsequent mass spectrometry. Although there was no direct match of differentially expressed proteins and genes, the majority of them belonged to identical pathways or networks. In conclusion, increasing genomic instability and a recurrent pattern of chromosomal imbalances as well as specific gene and protein expression changes correlate with distinct stages of colorectal cancer progression. Chromosomal aneuploidies directly affect average resident gene expression levels, thereby contributing to a massive deregulation of the cellular transcriptome. The identification of novel genes and proteins might deliver molecular targets for diagnostic and therapeutic interventions. This article contains Supplementary Material available at http:// www.interscience.wiley.com/jpages/1045-2257/suppmat. (c) 2006 Wiley-Liss, Inc.(dagger) C1 NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Pathol & Oncol, Unit Canc Proteom, Stockholm, Sweden. Univ Schleswig Holstein, Dept Surg, Lubeck, Germany. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Univ Schleswig Holstein, Inst Pathol, Lubeck, Germany. RP Habermann, JK (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH, 50 S Dr,Rm 1408, Bethesda, MD 20892 USA. EM habermaj@mail.nih.gov RI Bruch, Hans-Peter/E-7731-2010; Habermann, Jens/E-2968-2010 FU Intramural NIH HHS NR 37 TC 69 Z9 70 U1 5 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JAN PY 2007 VL 46 IS 1 BP 10 EP 26 DI 10.1002/gcc.20382 PG 17 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 106MH UT WOS:000242104200002 PM 17044061 ER PT J AU Rampersaud, E Morris, RW Weinberg, CR Speer, MC Martin, ER AF Rampersaud, E. Morris, R. W. Weinberg, C. R. Speer, M. C. Martin, E. R. TI Power calculations for likelihood ratio tests for offspring genotype risks, maternal effects, and parent-of-origin (POO) effects in the presence of missing parental genotypes when unaffected siblings are available SO GENETIC EPIDEMIOLOGY LA English DT Article DE family-based association; candidate gene tests; imprinting; parent-of-origin; maternal effects ID FAMILY-BASED ASSOCIATION; REELIN GENE ALLELES; LOG-LINEAR APPROACH; RELATIVE-RISKS; TRIAD DATA; LINKAGE; AUTISM; TRANSMISSION; DISORDERS AB Genotype-based likelihood-ratio tests (LRT) of association that examine maternal and parent-of-origin effects have been previously developed in the framework of log-linear and conditional logistic regression models. In the situation where parental genotypes are missing, the expectation-maximization (EM) algorithm has been incorporated in the log-linear approach to allow incomplete triads to contribute to the LRT. We present an extension to this model which we call the Combined_LRT that incorporates additional information from the genotypes of unaffected siblings to improve assignment of incompletely typed families to mating type categories, thereby improving inference of missing parental data. Using simulations involving a realistic array of family structures, we demonstrate the validity of the Combined LRT under the null hypothesis of no association and provide power comparisons under varying levels of missing data and using sibling genotype data. We demonstrate the improved power of the Combined LRT compared with the family-based association test (FBAT), another widely used association test. Lastly, we apply the Combined_LRT to a candidate gene analysis in Autism families, some of which have missing parental genotypes. We conclude that the proposed log-linear model will be an important tool for future candidate gene studies, for many complex diseases where unaffected siblings can often be ascertained and where epigenetic factors such as imprinting may play a role in disease etiology. C1 Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Anesthesia, Durham, NC 27710 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Martin, ER (reprint author), Duke Univ, Med Ctr, Ctr Human Genet, 5959 LaSalle St,3445, Durham, NC 27710 USA. EM Eden.Martin@duke.edu FU Intramural NIH HHS [Z01 ES040007-11]; NIEHS NIH HHS [P30 ES011961, U19 ES011375, ES11375, ES11961]; NINDS NIH HHS [NS36768, F31 NS046249, R01 NS039818, NS046249, NS26630, NS39818, P01 NS026630, R01 NS036768] NR 28 TC 10 Z9 10 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2007 VL 31 IS 1 BP 18 EP 30 DI 10.1002/gepi.20189 PG 13 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 116XX UT WOS:000242838200003 PM 17096358 ER PT S AU Subramanian, S Krishna, MC AF Subramanian, S. Krishna, M. C. BE Achilefu, S Bornhop, DJ Raghavachari, R Savitsky, AP Wachter, RM TI Free-radical probes for functional in vivo EPR imaging - art. no. 644904 SO Genetically Engineered and Optical Probes for Biomedical Applications IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Genetically Engineered and Optical Probes for Biomedical Applications IV CY JAN 23-24, 2007 CL San Jose, CA SP SPIE DE free radicals; spin probes; EPR imaging; oxymetry; oxidative stress; tumor hypoxia; Nitric oxide; spin trapping; functional imaging; nitroxides ID ELECTRON-SPIN-RESONANCE; MAGNETIC-RESONANCE; LITHIUM PHTHALOCYANINE; NITRIC-OXIDE; ELECTROCHEMICAL PREPARATION; OXYGEN CONCENTRATION; LIPID-PEROXIDATION; OXIDATIVE STRESS; CONTINUOUS-WAVE; OXIMETRY PROBE AB Electron paramagnetic resonance imaging (EPRI) is one of the recent functional imaging modalities that can provide valuable in vivo physiological information on its own merit and aids as a complimentary imaging technique to MRI and PET of tissues especially with respect to in vivo pO(2) (oxygen partial pressure), redox status and pharmacology. EPR imaging mainly deals with the measurement of distribution and in vivo dynamics and redox changes using special nontoxic paramagnetic spin probes that can be infused into the object of investigation. These spin probes should be characterized by simple EPR spectra, preferably with narrow EPR lines. The line width should be reversibly sensitive to the concentration of in Vivo pO(2) with a linear dependence. Several non-toxic paramagnetic probes, some particulate and insoluble and others water-soluble and infusible (by intravenous or intramuscular injection) have been developed which can be effectively used to quantitatively assess tissue redox. status, and tumor hypoxia. Quantitative assessment of the redox status of tissue in vivo is important in investigating oxidative stress, and that of tissue pO(2) is very important in radiation oncology. Other areas in which EPR imaging and oxymetry may help are in the investigation of tumor-angiogenesis, wound healing, oxygenation of tumor tissue by the ingestion of oxygen-rich gases, etc. The correct choice of the spin probe will depend on the modality of measurement (whether by CW or time-domain EPR imaging) and the particular physiology interrogated. Examples of the available spin probes and some EPR imaging applications employing them are presented. C1 NCI, Natl Canc Inst, NIH, Canc Res Ctr,Radiat Biol Branch, Bethesda, MD 20892 USA. RP Subramanian, S (reprint author), NCI, Natl Canc Inst, NIH, Canc Res Ctr,Radiat Biol Branch, Bethesda, MD 20892 USA. NR 98 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6562-7 J9 P SOC PHOTO-OPT INS PY 2007 VL 6449 BP 44904 EP 44904 AR 644904 DI 10.1117/12.700872 PG 16 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BGC15 UT WOS:000245977300002 ER PT S AU Kobayashi, H Hama, Y Koyama, Y Barrett, T Urano, Y Choyke, PL AF Kobayashi, Hisataka Hama, Yakihiro Koyama, Yoshinori Barrett, Tristan Urano, Yasuteru Choyke, Peter L. BE Achilefu, S Bornhop, DJ Raghavachari, R Savitsky, AP Wachter, RM TI Whole-hody multicolor spectrally resolved fluorescence imaging for development of target-specific optical contrast agents using genetically engineered probes - art. no. 644914 SO Genetically Engineered and Optical Probes for Biomedical Applications IV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Genetically Engineered and Optical Probes for Biomedical Applications IV CY JAN 23-24, 2007 CL San Jose, CA SP SPIE DE cancer; spectral fluorescence imaging; fluorescent probe; fluorescent protein; sensitivity; specificity; molecular imaging; molecular targeting AB Target-specific contrast agents are being developed for the molecular imaging of cancer. Optically detectable target-specific agents are promising for clinical applications because of their high sensitivity and specificity. Pre clinical testing is needed, however, to validate the actual sensitivity and specificity of these agents in animal models, and involves both conventional histology and immunohistochemistry, which requires large numbers of animals and samples with costly handling. However, a superior validation tool takes advantage of genetic engineering technology whereby cell lines are transfected with genes that induce the target cell to produce fluorescent proteins with characteristic emission spectra thus, identifying them as cancer cells. Multicolor fluorescence imaging of these genetically engineered probes can provide rapid validation of newly developed exogenous probes that fluoresce at different wavelengths. For example, the plasmid containing the gene encoding red fluorescent protein (RFP) was transfected into cell lines previously developed to either express or not-express specific cell surface receptors. Various antibody-based or receptor ligand-based optical contrast agents with either green or near infrared fluorophores were developed to concurrently target and validate cancer cells and their positive and negative controls, such as P-D-galactose receptor, HER1 and HER2 in a single animal/organ. Spectrally resolved fluorescence multicolor imaging was used to detect separate fluorescent emission spectra from the exogenous agents and RFP. Therefore, using this in vivo imaging technique, we were able to demonstrate the sensitivity and specificity of the target-specific optical contrast agents, thus reducing the number of animals needed to conduct these experiments. C1 Ctr Canc Res, Natl Canc Inst, NIH, Mol Imaging Program, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Ctr Canc Res, Natl Canc Inst, NIH, Mol Imaging Program, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6562-7 J9 P SOC PHOTO-OPT INS PY 2007 VL 6449 BP 44914 EP 44914 AR 644914 DI 10.1117/12.724241 PG 10 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BGC15 UT WOS:000245977300027 ER PT J AU Stein, KK Davis, ES Hays, T Golden, A AF Stein, Kathryn K. Davis, Edward S. Hays, Thomas Golden, Andy TI Components of the spindle assembly checkpoint regulate the anaphase-promoting complex during meiosis in Caenorhabditis elegans SO GENETICS LA English DT Article ID AGING-ASSOCIATED PHENOTYPES; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; CHROMOSOME SEGREGATION; FUNCTIONAL-ANALYSIS; PROPER CHROMOSOME; PROTEIN FAMILY; MOUSE OOCYTES; CYCLIN-B; MITOSIS AB Temperature-sensitive mutations in subunits of the Caenorhabditis elegans anaphase-promoting complex (APC) arrest at metaphase of meiosis I at the restrictive temperature. Embryos depleted of the APC coactivator FZY-1 by RNAi also arrest at this stage. To identify regulators and potential substrates of the APC, we performed a genetic suppressor screen with a weak allele of the APC subunit MAT-3/CDC23/APC8, whose defects are specific to meiosis. Twenty-seven suppressors that resulted in embryonic viability and larval development at the restrictive temperature were isolated. We have identified the molecular lesions in 18 of these suppressors, which correspond to five genes. In addition to a single intragenic suppressor, we found mutations in the APC co-activatorfzy-1 and in three spindle assembly checkpoint genes, mdf- 7, mdf-2, and mdf 3/san-1, orthologs of Mad 1, Mad2, and Mad3, respectively. Reduction-of-function alleles of mdf-2 and mdf-3 suppress A-PC mutants and exhibit pleiotropic phenotypes in an otherwise wild-type background. Analysis of a single separation-offunction allele of mdf-1 suggests that MDF-1 has a dual role during development. These studies provide evidence that components of the spindle assembly checkpoint may regulate the metaphaseto-anaphase transition in the absence of spindle damage during C. elegans mciosis. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Golden, A (reprint author), NIDDK, Lab Biochem & Genet, NIH, 8 Ctr Dr,MSC 0840,Bldg 8,Room 323, Bethesda, MD 20892 USA. EM andyg@mail.nih.gov FU Intramural NIH HHS NR 50 TC 26 Z9 41 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2007 VL 175 IS 1 BP 107 EP 123 DI 10.1534/genetics.106.059105 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 135UV UT WOS:000244180300011 PM 17057243 ER PT B AU Thorgeirsson, SS AF Thorgeirsson, S. S. BE Blum, HE Haussinger, D Cox, DW Jansen, PLM TI Microarray analysis and liver diseases SO Genetics in Liver Diseases SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 156 on Genetics in Liver Diseases CY OCT 08-09, 2006 CL Freiburg, GERMANY ID HUMAN HEPATOCELLULAR-CARCINOMA; ACUTE MYELOID-LEUKEMIA; FUNCTIONAL GENOMICS; EXPRESSION SIGNATURE; MOLECULAR-FEATURES; PROSTATE-CANCER; SURVIVAL; PREDICTION; CELLS C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-6392-3 J9 FALK SYMP PY 2007 VL 156 BP 8 EP 11 PG 4 WC Gastroenterology & Hepatology; Genetics & Heredity; Medicine, Research & Experimental SC Gastroenterology & Hepatology; Genetics & Heredity; Research & Experimental Medicine GA BGT84 UT WOS:000250477300002 ER PT J AU Brody, T Rasband, W Baler, K Kuzin, A Kundu, M Odenwald, WF AF Brody, Thomas Rasband, Wayne Baler, Kevin Kuzin, Alexander Kundu, Mukta Odenwald, Ward F. TI cis-DECODER discovers constellations of conserved DNA sequences shared among tissue-specific enhancers SO GENOME BIOLOGY LA English DT Review DE comparative genomics; evolution; enhancer structure and function ID OF-SPLIT COMPLEX; REGULATORY ELEMENTS DIRECT; DEVELOPING NERVOUS-SYSTEM; NEURAL STEM-CELLS; HOMEO BOX PROTEIN; DROSOPHILA-EMBRYO; GENE-EXPRESSION; TRANSCRIPTION FACTOR; SEGMENTATION GENE; BINDING-SITES AB A systematic approach is described for analysis of evolutionarily conserved cis-regulatory DNA using cis-Decoder, a tool for discovery of conserved sequence elements that are shared between similarly regulated enhancers. Analysis of 2,086 conserved sequence blocks ( CSBs), identified from 135 characterized enhancers, reveals most CSBs consist of shorter overlapping/adjacent elements that are either enhancer type-specific or common to enhancers with divergent regulatory behaviors. Our findings suggest that enhancers employ overlapping repertoires of highly conserved core elements. C1 NINDS, Neural Cell Fate Determinant Sect, NIH, Bethesda, MD 20892 USA. NIMH, Off Sci Directorate, IRP, NIH, Bethesda, MD 20892 USA. RP Odenwald, WF (reprint author), NINDS, Neural Cell Fate Determinant Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM wsr@nih.gov; kb263@cornell.edu; kuzina@mail.nih.gov; muktakundu@mail.nih.gov; ward@codon.nih.gov FU Intramural NIH HHS NR 119 TC 13 Z9 13 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 5 AR R75 DI 10.1186/gb-2007-8-5-r75 PG 52 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 175AA UT WOS:000246983100027 PM 17490485 ER PT J AU Clark, TG Andrew, T Cooper, GM Margulies, EH Mullikin, JC Balding, DJ AF Clark, Taane G. Andrew, Toby Cooper, Gregory M. Margulies, Elliott H. Mullikin, James C. Balding, David J. TI Functional constraint and small insertions and deletions in the ENCODE regions of the human genome SO GENOME BIOLOGY LA English DT Article ID REGULATORY ELEMENTS; COPY-NUMBER; POLYMORPHISMS; IDENTIFICATION; CHIMPANZEE; SEQUENCE; PROJECT; GENES; 1-PERCENT; CHROMATIN AB Background: We describe the distribution of indels in the 44 Encyclopedia of DNA Elements (ENCODE) regions (about 1% of the human genome) and evaluate the potential contributions of small insertion and deletion polymorphisms (indels) to human genetic variation. We relate indels to known genomic annotation features and measures of evolutionary constraint. Results: Indel rates are observed to be reduced approximately 20-fold to 60-fold in exonic regions, 5-fold to 10-fold in sequence that exhibits high evolutionary constraint in mammals, and up to 2-fold in some classes of regulatory elements (for instance, formaldehyde assisted isolation of regulatory elements [FAIRE] and hypersensitive sites). In addition, some noncoding transcription and other chromatin mediated regulatory sites also have reduced indel rates. Overall indel rates for these data are estimated to be smaller than single nucleotide polymorphism (SNP) rates by a factor of approximately 2, with both rates measured as base pairs per 100 kilobases to facilitate comparison. Conclusion: Indel rates exhibit a broadly similar distribution across genomic features compared with SNP density rates, with a reduction in rates in coding transcription and evolutionarily constrained sequence. However, unlike indels, SNP rates do not appear to be reduced in some noncoding functional sequences, such as pseudo-exons, and FAIRE and hypersensitive sites. We conclude that indel rates are greatly reduced in transcribed and evolutionarily constrained DNA, and discuss why indel (but not SNP) rates appear to be constrained at some regulatory sites. C1 [Clark, Taane G.; Andrew, Toby; Balding, David J.] Imperial Coll, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Cooper, Gregory M.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Margulies, Elliott H.; Mullikin, James C.] NIH, NHGRI, Bethesda, MD 20892 USA. RP Clark, TG (reprint author), Imperial Coll, Dept Epidemiol & Publ Hlth, Norfolk Pl, London W2 1PG, England. EM taane.clark@well.ox.ac.uk RI Cooper, Gregory/D-6914-2011; Balding, David/G-9898-2011 OI Cooper, Gregory/0000-0001-5509-9923; Andrew, Toby/0000-0001-8838-4384; Balding, David/0000-0002-1480-6115 FU Medical Research Council [G0300766] NR 34 TC 17 Z9 17 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 9 AR R180 DI 10.1186/gb-2007-8-9-r180 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 247SO UT WOS:000252100800006 PM 17784950 ER PT J AU Cui, YX McBride, SJ Boyd, WA Alper, S Freedman, JH AF Cui, Yuxia McBride, Sandra J. Boyd, Windy A. Alper, Scott Freedman, Jonathan H. TI Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity SO GENOME BIOLOGY LA English DT Article ID FUNCTIONAL GENOMIC ANALYSIS; WIDE EXPRESSION PATTERNS; DNA MICROARRAY ANALYSIS; C-ELEGANS; HEAVY-METAL; SACCHAROMYCES-CEREVISIAE; PHYTOCHELATIN SYNTHASE; METALLOTHIONEIN GENES; TRANSCRIPTION FACTOR; RNA INTERFERENCE AB Background: Exposure to cadmium is associated with a variety of human diseases. At low concentrations, cadmium activates the transcription of stress-responsive genes, which can prevent or repair the adverse effects caused by this metal. Results: Using Caenorhabditis elegans, 290 genes were identified that are differentially expressed (> 1.5- fold) following a 4 or 24 hour exposure to cadmium. Several of these genes are known to be involved in metal detoxification, including mtl-1, mtl-2, cdr-1 and ttm-1, confirming the efficacy of the study. The majority, however, were not previously associated with metal-responsiveness and are novel. Gene Ontology analysis mapped these genes to cellular/ion trafficking, metabolic enzymes and proteolysis categories. RNA interference-mediated inhibition of 50 cadmium-responsive genes resulted in an increased sensitivity to cadmium toxicity, demonstrating that these genes are involved in the resistance to cadmium toxicity. Several functional protein interacting networks were identified by interactome analysis. Within one network, the signaling protein KEL-8 was identified. Kel-8 protects C. elegans from cadmium toxicity in a mek-1 (MAPKK)-dependent manner. Conclusion: Because many C. elegans genes and signal transduction pathways are evolutionarily conserved, these results may contribute to the understanding of the functional roles of various genes in cadmium toxicity in higher organisms. C1 Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC 27708 USA. Natl Inst Environm Hlth Sci, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NHLBI, Lab Environm Lung Dis, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27707 USA. RP Freedman, JH (reprint author), Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC 27708 USA. EM freedma1@niehs.nih.gov OI Boyd, Windy/0000-0003-3803-3716 FU Intramural NIH HHS; NIEHS NIH HHS [R01 ES009949, R01ES009949, U19 ES011375, U19ES011375] NR 65 TC 81 Z9 99 U1 0 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 6 AR R122 DI 10.1186/gb-2007-8-6-r122 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 196NB UT WOS:000248488200030 PM 17592649 ER PT J AU Curtis, C Landis, GN Folk, D Wehr, NB Hoe, N Waskar, M Abdueva, D Skvortsov, D Ford, D Luu, A Badrinath, A Levine, RL Bradley, TJ Tavare, S Tower, J AF Curtis, Christina Landis, Gary N. Folk, Donna Wehr, Nancy B. Hoe, Nicholas Waskar, Morris Abdueva, Diana Skvortsov, Dmitriy Ford, Daniel Luu, Allan Badrinath, Ananth Levine, Rodney L. Bradley, Timothy J. Tavare, Simon Tower, John TI Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes SO GENOME BIOLOGY LA English DT Review ID ANTIOXIDANT RESPONSE ELEMENT; NEMATODE CAENORHABDITIS-ELEGANS; MANGANESE SUPEROXIDE-DISMUTASE; LIVED DAF-2 MUTANTS; OXIDATIVE STRESS; C-ELEGANS; LONGEVITY ASSURANCE; GENOME-WIDE; TRANSGENE EXPRESSION; ACATALASEMIC MUTANTS AB Background: Several interventions increase lifespan in model organisms, including reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO transcription factor activation, dietary restriction, and superoxide dismutase (SOD) over-expression. One question is whether these manipulations function through different mechanisms, or whether they intersect on common processes affecting aging. Results: A doxycycline-regulated system was used to over-express manganese-SOD (MnSOD) in adult Drosophila, yielding increases in mean and maximal lifespan of 20%. Increased lifespan resulted from lowered initial mortality rate and required MnSOD over-expression in the adult. Transcriptional profiling indicated that the expression of specific genes was altered by MnSOD in a manner opposite to their pattern during normal aging, revealing a set of candidate biomarkers of aging enriched for carbohydrate metabolism and electron transport genes and suggesting a true delay in physiological aging, rather than a novel phenotype. Strikingly, cross-dataset comparisons indicated that the pattern of gene expression caused by MnSOD was similar to that observed in long-lived Caenorhabditis elegans insulin-like signaling mutants and to the xenobiotic stress response, thus exposing potential conserved longevity promoting genes and implicating detoxification in Drosophila longevity. Conclusion: The data suggest that MnSOD up-regulation and a retrograde signal of reactive oxygen species from the mitochondria normally function as an intermediate step in the extension of lifespan caused by reduced insulin-like signaling in various species. The results implicate a species-conserved net of coordinated genes that affect the rate of senescence by modulating energetic efficiency, purine biosynthesis, apoptotic pathways, endocrine signals, and the detoxification and excretion of metabolites. C1 [Curtis, Christina; Landis, Gary N.; Hoe, Nicholas; Waskar, Morris; Abdueva, Diana; Skvortsov, Dmitriy; Ford, Daniel; Luu, Allan; Badrinath, Ananth; Tavare, Simon; Tower, John] Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA. [Folk, Donna; Bradley, Timothy J.] Univ Calif Irvine, Dept Ecol & Evolut Biol, Irvine, CA 92717 USA. [Wehr, Nancy B.; Levine, Rodney L.] NHLBI, Biochem Lab, Bethesda, MD 20817 USA. [Abdueva, Diana] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Pathol, Los Angeles, CA 90089 USA. [Abdueva, Diana] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Lab Med, Los Angeles, CA 90089 USA. [Tavare, Simon] Univ Cambridge, Dept Oncol, Cambridge CB2 2XZ, England. RP Tower, J (reprint author), Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA. EM jtower@usc.edu RI Levine, Rodney/D-9885-2011; OI Curtis, Christina/0000-0003-0166-3802 FU NIA NIH HHS [AG00093, AG11644, AG11833, R01 AG011833, T32 AG000093]; NIGMS NIH HHS [GM67243, R01 GM067243] NR 129 TC 82 Z9 86 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 12 AR R262 DI 10.1186/gb-2007-8-12-r262 PG 27 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 266QJ UT WOS:000253451800010 PM 18067683 ER PT J AU del Sol, A Arauzo-Bravo, MJ Moya, DA Nussinov, R AF del Sol, Antonio Arauzo-Bravo, Marcos J. Moya, Dolors Amoros Nussinov, Ruth TI Modular architecture of protein structures and allosteric communications: potential implications for signaling proteins and regulatory linkages SO GENOME BIOLOGY LA English DT Article DE modules; communication; allostery; network; transmission of information/; protein architecture ID SITE-DIRECTED MUTAGENESIS; CAMP-RECEPTOR-PROTEIN; GLYCOGEN-PHOSPHORYLASE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; PYRUVATE-KINASE; BINDING-SITE; MACROMOLECULAR MOTIONS; CONFORMATIONAL-CHANGES; CYTOCHROME P450ERYF AB Background : Allosteric communications are vital for cellular signaling. Here we explore a relationship between protein architectural organization and shortcuts in signaling pathways. Results : We show that protein domains consist of modules interconnected by residues that mediate signaling through the shortest pathways. These mediating residues tend to be located at the inter-modular boundaries, which are more rigid and display a larger number of long-range interactions than intra-modular regions. The inter-modular boundaries contain most of the residues centrally conserved in the protein fold, which may be crucial for information transfer between amino acids. Our approach to modular decomposition relies on a representation of protein structures as residue-interacting networks, and removal of the most central residue contacts, which are assumed to be crucial for allosteric communications. The modular decomposition of 100 multi-domain protein structures indicates that modules constitute the building blocks of domains. The analysis of 13 allosteric proteins revealed that modules characterize experimentally identified functional regions. Based on the study of an additional functionally annotated dataset of 115 proteins, we propose that high-modularity modules include functional sites and are the basic functional units. We provide examples ( the G alpha(s) subunit and P450 cytochromes) to illustrate that the modular architecture of active sites is linked to their functional specialization. Conclusions : Our method decomposes protein structures into modules, allowing the study of signal transmission between functional sites. A modular configuration might be advantageous: it allows signaling proteins to expand their regulatory linkages and may elicit a broader range of control mechanisms either via modular combinations or through modulations of inter-modular linkages. C1 Fujirebio Inc, Div Res & Dev, Bioinformat Res Unit, Hachioji, Tokyo 1920031, Japan. SAIC Frederick Inc, Basic Res Program, Ctr Canc Res, Nanobiol Program,Natl Canc Inst, Frederick, MD 21702 USA. Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP del Sol, A (reprint author), Fujirebio Inc, Div Res & Dev, Bioinformat Res Unit, 51 Komiya Cho, Hachioji, Tokyo 1920031, Japan. EM ao-mesa@fujirebio.co.jp; mararabra@yahoo.co.uk; ds-amoros@fujirebio.co.jp; ruthn@ncifcrf.gov RI Marcos, Arauzo-Bravo/A-1706-2011 OI Marcos, Arauzo-Bravo/0000-0002-3264-464X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 73 TC 59 Z9 59 U1 2 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 5 AR r92 DI 10.1186/gb-2007-8-5-r92 PG 31 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 175AA UT WOS:000246983100021 PM 17531094 ER PT J AU Eichler, GS Reimers, M Kane, D Weinstein, JN AF Eichler, Gabriel S. Reimers, Mark Kane, David Weinstein, John N. TI The LeFE algorithm: embracing the complexity of gene expression in the interpretation of microarray data SO GENOME BIOLOGY LA English DT Article ID CANCER CELL-LINES; BREAST-CANCER; CIGARETTE-SMOKE; RANDOM FOREST; CLASSIFICATION; GEFITINIB; ONTOLOGY; PATHWAY; TOOL; PROLIFERATION AB Interpretation of microarray data remains a challenge, and most methods fail to consider the complex, nonlinear regulation of gene expression. To address that limitation, we introduce Learner of Functional Enrichment (LeFE), a statistical/machine learning algorithm based on Random Forest, and demonstrate it on several diverse datasets: smoker/never smoker, breast cancer classification, and cancer drug sensitivity. We also compare it with previously published algorithms, including Gene Set Enrichment Analysis. LeFE regularly identifies statistically significant functional themes consistent with known biology. C1 [Eichler, Gabriel S.; Reimers, Mark; Kane, David; Weinstein, John N.] NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Eichler, Gabriel S.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Reimers, Mark] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA 23284 USA. [Kane, David] SRA Int, Fairfax, VA 22033 USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bldg 10, Bethesda, MD 20892 USA. EM weinstein@dtpax2.ncifcrf.gov NR 49 TC 11 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 9 AR R187 DI 10.1186/gb-2007-8-9-r187 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 247SO UT WOS:000252100800013 PM 17845722 ER PT J AU Fox, RM Watson, JD Von Stetina, SE McDermott, J Brodigan, TM Fukushige, T Krause, M Miller, DM AF Fox, Rebecca M. Watson, Joseph D. Von Stetina, Stephen E. McDermott, Joan Brodigan, Thomas M. Fukushige, Tetsunari Krause, Michael Miller, David M., III TI The embryonic muscle transcriptome of Caenorhabditis elegans SO GENOME BIOLOGY LA English DT Article ID MYOSIN HEAVY-CHAIN; BODY-WALL MUSCLE; GENE-EXPRESSION OMNIBUS; RECEPTOR ALPHA-SUBUNIT; C-ELEGANS; NEUROMUSCULAR-JUNCTION; SYNAPTIC-TRANSMISSION; NUCLEAR RECEPTOR; THICK FILAMENTS; MUTATIONS AB Background: The force generating mechanism of muscle is evolutionarily ancient; the fundamental structural and functional components of the sarcomere are common to motile animals throughout phylogeny. Recent evidence suggests that the transcription factors that regulate muscle development are also conserved. Thus, a comprehensive description of muscle gene expression in a simple model organism should define a basic muscle transcriptome that is also found in animals with more complex body plans. To this end, we applied microarray profiling of Caenorhabtidis elegans cells (MAPCeL) to muscle cell populations extracted from developing C. elegans embryos. Results: We used fluorescence-activated cell sorting to isolate myo-3::green fluorescent protein (GFP) positive muscle cells, and their cultured derivatives, from dissociated early C. elegans embryos. Microarray analysis identified 7,070 expressed genes, 1,312 of which are enriched in the myo-3::GFP positive cell population relative to the average embryonic cell. The muscle enriched gene set was validated by comparisons with known muscle markers, independently derived expression data, and GFP reporters in transgenic strains. These results confirm the utility of MAPCeL for cell type specific expression profiling and reveal that 60% of these transcripts have human homologs. Conclusion: This study provides a comprehensive description of gene expression in developing C. elegans embryonic muscle cells. The finding that more than half of these muscle enriched transcripts encode proteins with human homologs suggests that mutant analysis of these genes in C. elegans could reveal evolutionarily conserved models of muscle gene function, with ready application to human muscle pathologies. C1 [Watson, Joseph D.; Miller, David M., III] Vanderbilt Univ, Grad Program Neurosci, Ctr Mol Neurosci, Nashville, TN 37232 USA. [McDermott, Joan; Brodigan, Thomas M.; Fukushige, Tetsunari; Krause, Michael] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. [Fox, Rebecca M.; Watson, Joseph D.; Von Stetina, Stephen E.; Miller, David M., III] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA. RP Miller, DM (reprint author), Vanderbilt Univ, Dept Cell & Dev Biol, 465 21st Ave S, Nashville, TN 37232 USA. EM david.miller@vanderbilt.edu OI Krause, Michael/0000-0001-6127-3940 FU NCI NIH HHS [P30 CA68485, P30 CA068485]; NEI NIH HHS [P30 EY008126, P30 EY08126]; NHGRI NIH HHS [U01 HG004263]; NHLBI NIH HHS [P01 HL6744]; NICHD NIH HHS [HD15052, P30 HD015052, T32 HD007502, T32 HD07502]; NIDDK NIH HHS [DK58749, P01 DK058212, P01 DK58212, P30 DK058404, P30 DK58404, P60 DK020593, P60 DK20593]; NIMH NIH HHS [T32 MH064913, T32 MH64913]; NINDS NIH HHS [F31 NS043068, F31 NS046293, F31 NS049743, R01 NS026115, R01 NS26115] NR 68 TC 49 Z9 81 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 9 AR R188 DI 10.1186/gb-2007-8-9-r188 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 247SO UT WOS:000252100800014 PM 17848203 ER PT J AU Herschkowitz, JI Simin, K Weigman, VJ Mikaelian, I Usary, J Hu, ZY Rasmussen, KE Jones, LP Assefnia, S Chandrasekharan, S Backlund, MG Yin, YZ Khramtsov, AI Bastein, R Quackenbush, J Glazer, RI Brown, PH Green, JE Kopelovich, L Furth, PA Palazzo, JP Olopade, OI Bernard, PS Churchill, GA Van Dyke, T Perou, CM AF Herschkowitz, Jason I. Simin, Karl Weigman, Victor J. Mikaelian, Igor Usary, Jerry Hu, Zhiyuan Rasmussen, Karen E. Jones, Laundette P. Assefnia, Shahin Chandrasekharan, Subhashini Backlund, Michael G. Yin, Yuzhi Khramtsov, Andrey I. Bastein, Roy Quackenbush, John Glazer, Robert I. Brown, Powel H. Green, Jeffrey E. Kopelovich, Levy Furth, Priscilla A. Palazzo, Juan P. Olopade, Olufunmilayo I. Bernard, Philip S. Churchill, Gary A. Van Dyke, Terry Perou, Charles M. TI Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors SO GENOME BIOLOGY LA English DT Article ID TAG TRANSGENIC MICE; MOLECULAR PORTRAITS; EPITHELIAL-CELLS; MICROARRAY DATA; BRCA1 MUTATIONS; MOUSE MODELS; KI-RAS; CANCER; PROFILES; PATTERNS AB Background Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from thirteen different murine models using DNA microarrays and compared the resulting data to that of human breast tumors. Results Unsupervised hierarchical clustering analysis showed that six models ( TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int., TgWAP9 Tag, and TgC3( 1)9 Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models ( TgWAP-T-181, TgMMTV-Wnt1, Brca1(Co/Co); TgMMTV-Cre; p53(+/-) and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors, however, these murine tumors lacked expression of ER and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER-subtype and were more similar to human luminal tumors. Conclusions Many of the defining characteristics of human subtypes were conserved among mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors. C1 Univ N Carolina, Ctr Canc, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Program Bioinformat & Computat Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. Jackson Lab, Bar Harbor, ME 04609 USA. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. Baylor Coll Med, Houston, TX 77030 USA. NCI, Lab Cellular Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA. Univ Chicago, Dept Med, Hematol Oncol Sect, Comm Genet, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Hematol Oncol Sect, Comm Canc Biol, Chicago, IL 60637 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Perou, CM (reprint author), Univ N Carolina, Ctr Canc, Lineberger Comprehens Canc Ctr, Campus Box 7295, Chapel Hill, NC 27599 USA. EM jih@unc.edu; Karl.Simin@umassmed.edu; weigman@gmail.com; igor.mikaelian@roche.com; usary@unc.edu; zhu@med.unc.edu; karen_rasmussen@med.unc.edu; ljone010@umaryland.edu; sa358@georgetown.edu; subhashini_chandrasekharan@med.unc.edu; michael.backlund@Vanderbilt.Edu; yiny@georgetown.edu; andrey1@uchicago.edu; roy.bastien@hci.utah.edu; john.quackenbush@hci.utah.edu; glazerr@georgetown.edu; pbrown@breastcenter.tmc.edu; jegreen@mail.nih.gov; kopelovich@nih.gov; paf3@georgetown.edu; Juan.Palazzo@jefferson.edu; folopade@medicine.bsd.uchicago.edu; phil.bernard@hci.utah.edu; gary.churchill@jax.org; tvdlab@med.unc.edu; cperou@med.unc.edu OI Perou, Charles/0000-0001-9827-2247 FU NCI NIH HHS [N01-CN-05024, N01-CN15044, N01-CN43308, N01CN43308, P50 CA058223, P50-CA58223-09A1, R01 CA046283, R01 CA101211, R01 CA101227, R01 CA112176, R01 CA112176-05, R01-CA-101227-01, R01-CA046283-16, R01-CA101211, T32 CA009686]; NIEHS NIH HHS [T32 ES007017, T32 ES07017] NR 55 TC 568 Z9 579 U1 6 U2 37 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 5 AR r76 DI 10.1186/gb-2007-8-5-r76 PG 34 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 175AA UT WOS:000246983100012 PM 17493263 ER PT J AU Hirst, M Delaney, A Rogers, SA Schnerch, A Persaud, DR O'Connor, MD Zeng, T Moksa, M Fichter, K Mah, D Go, A Morin, RD Baross, A Zhao, YJ Khattra, J Prabhu, AL Pandoh, P McDonald, H Asano, J Dhalla, N Ma, K Lee, S Ally, A Chahal, N Menzies, S Siddiqui, A Holt, R Jones, S Gerhard, DS Thomson, JA Eaves, CJ Marra, MA AF Hirst, Martin Delaney, Allen Rogers, Sean A. Schnerch, Angelique Persaud, Deryck R. O'Connor, Michael D. Zeng, Thomas Moksa, Michelle Fichter, Keith Mah, Diana Go, Anne Morin, Ryan D. Baross, Agnes Zhao, Yongjun Khattra, Jaswinder Prabhu, Anna-Liisa Pandoh, Pawan McDonald, Helen Asano, Jennifer Dhalla, Noreen Ma, Kevin Lee, Stephanie Ally, Adrian Chahal, Neil Menzies, Stephanie Siddiqui, Asim Holt, Robert Jones, Steven Gerhard, Daniela S. Thomson, James A. Eaves, Connie J. Marra, Marco A. TI LongSAGE profiling of nine human embryonic stem cell lines SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION; PROCESSED PSEUDOGENES; MOLECULAR SIGNATURE; HUMAN GENOME; MOUSE EMBRYOS; SELF-RENEWAL; DIFFERENTIATION; PLURIPOTENCY; GROWTH; CDNA AB To facilitate discovery of novel human embryonic stem cell (ESC) transcripts, we generated 2.5 million LongSAGE tags from 9 human ESC lines. Analysis of this data revealed that ESCs express proportionately more RNA binding proteins compared with terminally differentiated cells, and identified novel ESC transcripts, at least one of which may represent a marker of the pluripotent state. C1 British Columbia Canc Agcy, Genom Sci Ctr, Vancouver, BC V5Z 1L3, Canada. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NCI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Sch Med, Madison, WI 53715 USA. Univ Wisconsin, Dept Anat, Sch Med, Madison, WI 53715 USA. RP Marra, MA (reprint author), British Columbia Canc Agcy, Genom Sci Ctr, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM mmarra@bcgsc.ca RI Hirst, Martin/C-3619-2009; Tang, Macy/B-9798-2014; Holt, Robert/C-3303-2009; Marra, Marco/B-5987-2008; Hirst, Martin/B-7684-2016; Jones, Steven/C-3621-2009 FU PHS HHS [N01-C0-12400] NR 68 TC 16 Z9 16 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 6 AR R113 DI 10.1186/gb-2007-8-6-r113 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 196NB UT WOS:000248488200021 PM 17570852 ER PT J AU Huang, DW Sherman, BT Tan, Q Collins, JR Alvord, WG Roayaei, J Stephens, R Baseler, MW Lane, HC Lempicki, RA AF Huang, Da Wei Sherman, Brad T. Tan, Qina Collins, Jack R. Alvord, W. Gregory Roayaei, Jean Stephens, Robert Baseler, Michael W. Lane, H. Clifford Lempicki, Richard A. TI The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists SO GENOME BIOLOGY LA English DT Article ID EXPRESSION DATA; MICROARRAY DATA; ONTO-TOOLS; SETS; ASSOCIATIONS; ANNOTATION; CATEGORIES; DESIGN AB The DAVID Gene Functional Classification Tool http://david.abcc.ncifcrf.gov uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context. C1 [Huang, Da Wei; Sherman, Brad T.; Tan, Qina; Baseler, Michael W.; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Alvord, W. Gregory; Roayaei, Jean] NCI, Comp Stat Serv, Data Management Serv, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. [Lane, H. Clifford] NIH, NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Lempicki, RA (reprint author), NCI, Lab Immunopathogenesis & Bioinformat, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM rlempicki@mail.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 37 TC 326 Z9 331 U1 4 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 9 AR R183 DI 10.1186/gb-2007-8-9-r183 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 247SO UT WOS:000252100800009 PM 17784955 ER PT J AU Koester, SE Insel, TR AF Koester, Susan E. Insel, Thomas R. TI Mouse maps of gene expression in the brain SO GENOME BIOLOGY LA English DT Review ID ATLAS AB The completion of the Allen Brain Atlas generated a great deal of press interest and enthusiasm from the research community. What does it do, and what other complementary resources increase its functionality?. C1 NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, Div Neurosci & Basic Behav Sci, Execut Blvd, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 12 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 5 AR 212 DI 10.1186/gb-2007-8-5-212 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 175AA UT WOS:000246983100002 PM 17521453 ER PT J AU Lobanov, AV Fomenko, DE Zhang, Y Sengupta, A Hatfield, DL Gladyshev, VN AF Lobanov, Alexey V. Fomenko, Dmitri E. Zhang, Yan Sengupta, Aniruddha Hatfield, Dolph L. Gladyshev, Vadim N. TI Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life SO GENOME BIOLOGY LA English DT Article ID SELENOCYSTEINE INSERTION SYSTEM; DIATOM THALASSIOSIRA-PSEUDONANA; OSTREOCOCCUS-TAURI CHLOROPHYTA; TRANSFER-RNA; GENETIC-CODE; SECIS RNA; GENOME; IDENTIFICATION; CHLAMYDOMONAS; SELENIUM AB Background: Selenocysteine ( Sec) is a selenium-containing amino acid that is co-translationally inserted into nascent polypeptides by recoding UGA codons. Selenoproteins occur in both eukaryotes and prokaryotes, but the selenoprotein content of organisms (selenoproteome) is highly variable and some organisms do not utilize Sec at all. Results: We analyzed the selenoproteomes of several model eukaryotes and detected 26 and 29 selenoprotein genes in the green algae Ostreococcus tauri and Ostreococcus lucimarinus, respectively, five in the social amoebae Dictyostelium discoideum, three in the fly Drosophila pseudoobscura, and 16 in the diatom Thalassiosira pseudonana, including several new selenoproteins. Distinct selenoprotein patterns were verified by metabolic labeling of O. tauri and D. discoideum with (75)Se. More than half of the selenoprotein families were shared by unicellular eukaryotes and mammals, consistent with their ancient origin. Further analyses identified massive, independent selenoprotein losses in land plants, fungi, nematodes, insects and some protists. Comparative analyses of selenoprotein-rich and -deficient organisms revealed that aquatic organisms generally have large selenoproteomes, whereas several groups of terrestrial organisms reduced their selenoproteomes through loss of selenoprotein genes and replacement of Sec with cysteine. Conclusion: Our data suggest many selenoproteins originated at the base of the eukaryotic domain and show that the environment plays an important role in selenoproteome evolution. In particular, aquatic organisms apparently retained and sometimes expanded their selenoproteomes, whereas the selenoproteomes of some terrestrial organisms were reduced or completely lost. These findings suggest a hypothesis that, with the exception of vertebrates, aquatic life supports selenium utilization, whereas terrestrial habitats lead to reduced use of this trace element due to an unknown environmental factor. C1 [Lobanov, Alexey V.; Fomenko, Dmitri E.; Zhang, Yan; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Sengupta, Aniruddha; Hatfield, Dolph L.] NCI, Natl Inst Hlth, Sect Mol Biol Selenium, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Gladyshev, Vadim/A-9894-2013 FU NIGMS NIH HHS [GM061603, R01 GM061603] NR 48 TC 90 Z9 95 U1 1 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 9 AR R198 DI 10.1186/gb-2007-8-9-r198 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 247SO UT WOS:000252100800024 PM 17880704 ER PT J AU Meyer, JN Boyd, WA Azzam, GA Haugen, AC Freedman, JH Van Houten, B AF Meyer, Joel N. Boyd, Windy A. Azzam, Greg A. Haugen, Astrid C. Freedman, Jonathan H. Van Houten, Bennett TI Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans SO GENOME BIOLOGY LA English DT Article ID GENOME-WIDE RNAI; RADIATION-SENSITIVE MUTANTS; DNA-DAMAGE RESPONSE; C-ELEGANS; GENE-EXPRESSION; UV-RADIATION; WILD-TYPE; PYRIMIDINE DIMERS; WERNER-SYNDROME; LIFE-SPAN AB Background Although Caenorhabditis elegans is an important model for the study of DNA damage-and repair-related processes such as aging, neurodegeneration and carcinogenesis, DNA repair is poorly characterized in this organism. We adapted a quantitative PCR assay to characterize repair of UVC radiation-induced DNA damage in Celegans, and then tested whether DNA repair rates were affected by age in adults. Results UVC radiation induced lesions in young adult Celegans with a slope of 0.4-0.5 lesions per 10kb DNA per 100 Joules/m(2), in both nuclear and mitochondrial targets. L1 and dauer larvae were > 5-fold more sensitive to lesion formation than young adults. Nuclear repair kinetics in a well-expressed nuclear gene were biphasic in non-gravid adult nematodes: a faster, first order ( t(1/2) similar to 16 h) phase lasting similar to 24 h and resulting in removal of similar to 60% of the photoproducts was followed by a much slower phase. Repair in 10 nuclear DNA regions was 15% and 50% higher in more actively transcribed regions in young and aging adults, respectively. Finally, repair was reduced 30-50% in each of the 10 nuclear regions in aging adults. However, this decrease in repair could not be explained by a reduction in expression of nucleotide excision repair genes, and we present a plausible mechanism, based on gene expression data, to explain this decrease. Conclusions Repair of UVC-induced DNA damage in Celegans is similar kinetically and genetically to repair in humans. Furthermore, this important repair process slows significantly in aging Celegans, the first whole organism in which this question has been addressed. C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Van Houten, B (reprint author), NIEHS, Genet Mol Lab, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM joel.meyer@duke.edu; boydw@niehs.nih.gov; azzamg@niehs.nih.gov; haugen@niehs.nih.gov; freema1@niehs.nih.gov; vanhout1@niehs.nih.gov OI Boyd, Windy/0000-0003-3803-3716 FU Intramural NIH HHS; NIEHS NIH HHS [T32 ES007031, T32-ES-007031] NR 97 TC 51 Z9 64 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 5 AR R70 DI 10.1186/gb-2007-8-5-r70 PG 40 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 175AA UT WOS:000246983100008 PM 17472752 ER PT J AU Panelli, MC Stashower, ME Slade, HB Smith, K Norwood, C Abati, A Fetsch, P Filie, A Walters, SA Astry, C Arico, E Zhao, YD Selleri, S Wang, E Marincola, FM AF Panelli, Monica C. Stashower, Mitchell E. Slade, Herbert B. Smith, Kina Norwood, Christopher Abati, Andrea Fetsch, Patricia Filie, Armando Walters, Shelley-Ann Astry, Calvin Arico, Eleonora Zhao, Yingdong Selleri, Silvia Wang, Ena Marincola, Francesco M. TI Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection SO GENOME BIOLOGY LA English DT Article ID ADAPTIVE IMMUNE-RESPONSES; HEPATITIS-C VIRUS; EXPRESSION PATTERNS; 5-PERCENT CREAM; DENDRITIC CELLS; GRANZYME-B; ACTIVATION; MELANOMA; IMMUNIZATION; INNATE AB Background: Imiquimod is a Toll-like receptor-7 agonist capable of inducing complete clearance of basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization of the early transcriptional events induced by imiquimod may provide insights about immunological events preceding acute tissue and/or tumor rejection. Results: We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (n = 22) or vehicle cream (n = 14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hours for 4 or 8 days). RNA was amplified and hybridized to 17.5 K cDNA arrays. All treatment schedules similarly affected the transcriptional profile of BCC; however, the q12 x 4 days regimen, associated with highest effectiveness, induced the most changes, with 637 genes unequivocally stimulated by imiquimod. A minority of transcripts (98 genes) confirmed previous reports of interferon-alpha involvement. The remaining 539 genes portrayed additional immunological functions predominantly involving the activation of cellular innate and adaptive immune-effector mechanisms. Importantly, these effector signatures recapitulate previous observations of tissue rejection in the context of cancer immunotherapy, acute allograft rejection and autoimmunity. Conclusion: This study, based on a powerful and reproducible model of cancer eradication by innate immune mechanisms, provides the first insights in humans into the early transcriptional events associated with immune rejection. This model is likely representative of constant immunological pathways through which innate and adaptive immune responses combine to induce tissue destruction. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Clin Skin Ctr No Virginia, Fairfax, VA 22033 USA. 3M Pharmaceut, St Paul, MN 55144 USA. Natl Naval Med Ctr, Dept Dermatol, Bethesda, MD 20889 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. Univ Milan, Dept Human Morphol, I-20133 Milan, Italy. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM Fmarincola@mail.cc.nih.gov NR 60 TC 58 Z9 59 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 1 AR R8 DI 10.1186/gb-2007-8-1-r8 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 144UF UT WOS:000244821100013 PM 17222352 ER PT J AU Rector, A Lemey, P Tachezy, R Mostmans, S Ghim, SJ Van Doorslaer, K Roelke, M Bush, M Montali, RJ Joslin, J Burk, RD Jenson, AB Sundberg, JP Shapiro, B Van Ranst, M AF Rector, Annabel Lemey, Philippe Tachezy, Ruth Mostmans, Sara Ghim, Shin-Je Van Doorslaer, Koenraad Roelke, Melody Bush, Mitchell Montali, Richard J. Joslin, Janis Burk, Robert D. Jenson, Alfred B. Sundberg, John P. Shapiro, Beth Van Ranst, Marc TI Ancient papillomavirus-host co-speciation in Felidae SO GENOME BIOLOGY LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; ROLLING-CIRCLE AMPLIFICATION; HUMAN-POPULATIONS; VIRUS; TYPE-1; CLONING; PROTEIN; COEVOLUTION; HYPERPLASIA; PHYLOGENY AB Background: Estimating evolutionary rates for slowly evolving viruses such as papillomaviruses ( PVs) is not possible using fossil calibrations directly or sequences sampled over a time-scale of decades. An ability to correlate their divergence with a host species, however, can provide a means to estimate evolutionary rates for these viruses accurately. To determine whether such an approach is feasible, we sequenced complete feline PV genomes, previously available only for the domestic cat ( Felis domesticus, FdPV1), from four additional, globally distributed feline species: Lynx rufus PV type 1, Puma concolor PV type 1, Panthera leo persica PV type 1, and Uncia uncia PV type 1. Results: The feline PVs all belong to the Lambdapapillomavirus genus, and contain an unusual second noncoding region between the early and late protein region, which is only present in members of this genus. Our maximum likelihood and Bayesian phylogenetic analyses demonstrate that the evolutionary relationships between feline PVs perfectly mirror those of their feline hosts, despite a complex and dynamic phylogeographic history. By applying host species divergence times, we provide the first precise estimates for the rate of evolution for each PV gene, with an overall evolutionary rate of 1.95 x 10(-8) ( 95% confidence interval 1.32 x 10(-8) to 2.47 x 10(-8)) nucleotide substitutions per site per year for the viral coding genome. Conclusion: Our work provides evidence for long-term virus-host co-speciation of feline PVs, indicating that viral diversity in slowly evolving viruses can be used to investigate host species evolution. These findings, however, should not be extrapolated to other viral lineages without prior confirmation of virus-host co-divergence. C1 Katholieke Univ Leuven, Rega Inst Med Res, Lab Clin & Epidemiol Virol, B-3000 Louvain, Belgium. Univ Oxford, Dept Zool, Oxford OX1 3PS, England. Inst Hematol & Blood Transfus, Dept Expt Virol, Prague 12822, Czech Republic. Univ Louisville, Brown Canc Ctr, Louisville, KY 40202 USA. Albert Einstein Coll Med, Ctr Comprehens Canc, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. SAIC Frederick Natl Canc Inst, Basic Res Program, Ft Detrick, MD 21702 USA. Smithsonian Conservat & Res Ctr, Natl Zool Pk, Front Royal, VA 22630 USA. Phoenix Zoo, Phoenix, AZ 85008 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Van Ranst, M (reprint author), Katholieke Univ Leuven, Rega Inst Med Res, Lab Clin & Epidemiol Virol, Minderbroeders Str, B-3000 Louvain, Belgium. EM marc.vanranst@uz.kuleuven.be OI Van Ranst, Marc/0000-0002-1674-4157 NR 41 TC 83 Z9 84 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 4 AR R57 DI 10.1186/gb-2007-8-4-r57 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 174ZY UT WOS:000246982900014 PM 17430578 ER PT J AU Rossi, L Salvetti, A Marincola, FM Lena, A Deri, P Mannini, L Batistoni, R Wang, E Gremigni, V AF Rossi, Leonardo Salvetti, Alessandra Marincola, Francesco M. Lena, Annalisa Deri, Paolo Mannini, Linda Batistoni, Renata Wang, Ena Gremigni, Vittorio TI Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile SO GENOME BIOLOGY LA English DT Article ID PLANARIAN DUGESIA-JAPONICA; HISTONE DEACETYLASES; TRANSCRIPTIONAL COREPRESSOR; C-MYC; N-COR; REGENERATION; PROTEIN; IDENTIFICATION; REPRESSION; BINDING AB Background: Mammalian stem cells are difficult to access experimentally; model systems that can regenerate offer an alternative way to characterize stem cell related genes. Planarian regeneration depends on adult pluripotent stem cells - the neoblasts. These cells can be selectively destroyed using X-rays, enabling comparison of organisms lacking stem cells with wild-type worms. Results: Using a genomic approach we produced an oligonucleotide microarray chip ( the Dj600 chip), which was designed using selected planarian gene sequences. Using this chip, we compared planarians treated with high doses of X-rays ( which eliminates all neoblasts) with wild-type worms, which led to identification of a set of putatively neoblast-restricted genes. Most of these genes are involved in chromatin modeling and RNA metabolism, suggesting that epigenetic modifications and post-transcriptional regulation are pivotal in neoblast regulation. Comparing planarians treated with low doses of X-rays ( after which some radiotolerant neoblasts re-populate the planarian body) with specimens irradiated with high doses and unirradiated control worms, we identified a group of genes that were upregulated as a consequence of low-dose X-ray treatment. Most of these genes encode proteins that are known to regulate the balance between death and survival of the cell; our results thus suggest that genetic programs that control neoblast cytoprotection, proliferation, and migration are activated by low-dose X-rays. Conclusion: The broad differentiation potential of planarian neoblasts is unparalleled by any adult stem cells in the animal kingdom. In addition to our validation of the Dj600 chip as a valuable platform, our work contributes to elucidating the molecular mechanisms that regulate the self-renewal and differentiation of neoblasts. C1 Univ Pisa, Dipartimento Morfol Umana & Biol Applicata, Sez Biol & Genet, I-56126 Pisa, Italy. Warren G Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dipartimento Biol, Unita Biol Cellulare & Sviluppo, I-56010 Pisa, Italy. RP Rossi, L (reprint author), Univ Pisa, Dipartimento Morfol Umana & Biol Applicata, Sez Biol & Genet, Via Volta, I-56126 Pisa, Italy. EM leoros@biomed.unipi.it OI SALVETTI, ALESSANDRA/0000-0002-9154-9773 NR 61 TC 66 Z9 71 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 4 AR R62 DI 10.1186/gb-2007-8-4-r62 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 174ZY UT WOS:000246982900019 PM 17445279 ER PT J AU Rubins, KH Hensley, LE Wahl-Jensen, V DiCaprio, KMD Young, HA Reed, DS Jahrling, PB Brown, PO Relman, DA Geisbert, TW AF Rubins, Kathleen H. Hensley, Lisa E. Wahl-Jensen, Victoria DiCaprio, Kathleen M. Daddario Young, Howard A. Reed, Douglas S. Jahrling, Peter B. Brown, Patrick O. Relman, David A. Geisbert, Thomas W. TI The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever SO GENOME BIOLOGY LA English DT Article ID NECROSIS-FACTOR RECEPTOR; VIRUS-INFECTED PATIENTS; SMALL GLYCOPROTEIN SGP; CYNOMOLGUS MACAQUES; ENDOTHELIAL-CELLS; HUMAN MACROPHAGES; MARBURG VIRUSES; RHESUS-MONKEYS; IFN-ALPHA; IN-VITRO AB Background: Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions, we examined the molecular features of EBOV infection in vivo. Results: Using high-density cDNA microarrays, we analyzed genome-wide host expression patterns in sequential blood samples from nonhuman primates infected with EBOV. The temporal program of gene expression was strikingly similar between animals. Of particular interest were features of the data that reflect the interferon response, cytokine signaling, and apoptosis. Transcript levels for tumor necrosis factor-alpha converting enzyme (TACE)/alpha-disintegrin and metalloproteinase (ADAM)-17 increased during days 4 to 6 after infection. In addition, the serum concentration of cleaved Ebola glycoprotein (GP(2) delta) was elevated in late-stage EBOV infected animals. Of note, we were able to detect changes in gene expression of more than 300 genes before symptoms appeared. Conclusion: These results provide the first genome-wide ex vivo analysis of the host response to systemic filovirus infection and disease. These data may elucidate mechanisms of viral pathogenesis and host defense, and may suggest targets for diagnostic and therapeutic development. C1 [Rubins, Kathleen H.; Relman, David A.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Rubins, Kathleen H.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. [Rubins, Kathleen H.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. [Hensley, Lisa E.; Wahl-Jensen, Victoria; DiCaprio, Kathleen M. Daddario; Reed, Douglas S.; Jahrling, Peter B.; Geisbert, Thomas W.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Young, Howard A.] NCI, Frederick, MD 21702 USA. [Brown, Patrick O.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Relman, David A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Relman, David A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. RP Rubins, KH (reprint author), Stanford Univ, Sch Med, Dept Microbiol & Immunol, 299 Campus Dr, Stanford, CA 94305 USA. EM rubins@wi.mit.edu OI Reed, Douglas/0000-0003-0076-9023 FU NIAID NIH HHS [AI54922, R01 AI054922] NR 69 TC 42 Z9 46 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 8 AR R174 DI 10.1186/gb-2007-8-8-r174 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 273NT UT WOS:000253938500026 PM 17725815 ER PT J AU Stajich, JE Dietrich, FS Roy, SW AF Stajich, Jason E. Dietrich, Fred S. Roy, Scott W. TI Comparative genomic analysis of fungal genomes reveals intron-rich ancestors SO GENOME BIOLOGY LA English DT Article ID EUKARYOTIC EVOLUTION; CRYPTOCOCCUS-NEOFORMANS; SPLICEOSOMAL INTRONS; SEQUENCE; GENES; YEAST; PHYLOGENY; DATABASE; GAIN; RNA AB Background: Eukaryotic protein-coding genes are interrupted by spliceosomal introns, which are removed from transcripts before protein translation. Many facets of spliceosomal intron evolution, including age, mechanisms of origins, the role of natural selection, and the causes of the vast differences in intron number between eukaryotic species, remain debated. Genome sequencing and comparative analysis has made possible whole genome analysis of intron evolution to address these questions. Results: We analyzed intron positions in 1,161 sets of orthologous genes across 25 eukaryotic species. We find strong support for an intron-rich fungus-animal ancestor, with more than four introns per kilobase, comparable to the highest known modern intron densities. Indeed, the fungus-animal ancestor is estimated to have had more introns than any of the extant fungi in this study. Thus, subsequent fungal evolution has been characterized by widespread and recurrent intron loss occurring in all fungal clades. These results reconcile three previously proposed methods for estimation of ancestral intron number, which previously gave very different estimates of ancestral intron number for eight eukaryotic species, as well as a fourth more recent method. We do not find a clear inverse correspondence between rates of intron loss and gain, contrary to the predictions of selection- based proposals for interspecific differences in intron number. Conclusion: Our results underscore the high intron density of eukaryotic ancestors and the widespread importance of intron loss through eukaryotic evolution. C1 [Stajich, Jason E.; Dietrich, Fred S.; Roy, Scott W.] Duke Univ, Inst Genom Sci & Policy, Ctr Genom Tecchnol, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Stajich, Jason E.] Univ Calif Berkeley, Miller Inst Basic Res, Berkeley, CA 94720 USA. [Stajich, Jason E.; Dietrich, Fred S.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA. [Roy, Scott W.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Stajich, JE (reprint author), Duke Univ, Inst Genom Sci & Policy, Ctr Genom Tecchnol, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. EM jason_stajich@berkeley.edu RI Stajich, Jason/C-7297-2008 OI Stajich, Jason/0000-0002-7591-0020 FU NINDS NIH HHS [NS042263-03, R01 NS042263] NR 62 TC 60 Z9 61 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 10 AR R223 DI 10.1186/gb-2007-8-10-r223 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 247SP UT WOS:000252100900021 PM 17949488 ER PT J AU Toscano, CD Prabhu, VV Langenbach, R Becker, KG Bosetti, F AF Toscano, Christopher D. Prabhu, Vinaykumar V. Langenbach, Robert Becker, Kevin G. Bosetti, Francesca TI Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain SO GENOME BIOLOGY LA English DT Article ID KAPPA-B PATHWAY; DOWN-REGULATION; METHIONINE ADENOSYLTRANSFERASE; MOLECULAR-MECHANISMS; PHOSPHOLIPASE A(2); KNOCKOUT MOUSE; MESSENGER-RNA; RAT-BRAIN; LOCALIZATION; SUBUNIT AB Background: Cyclooxygenase (COX)-1 and COX-2 produce prostanoids from arachidonic acid and are thought to have important yet distinct roles in normal brain function. Deletion of COX-1 or COX-2 results in profound differences both in brain levels of prostaglandin E2 and in activation of the transcription factor nuclear factor-kappa B, suggesting that COX-1 and COX-2 play distinct roles in brain arachidonic acid metabolism and regulation of gene expression. To further elucidate the role of COX isoforms in the regulation of the brain transcriptome, microarray analysis of gene expression in the cerebral cortex and hippocampus of mice deficient in COX-1 (COX-1(-/-)) or COX-2 (COX-2(-/-)) was performed. Results: A majority (> 93%) of the differentially expressed genes in both the cortex and hippocampus were altered in one COX isoform knockout mouse but not the other. The major gene function affected in all genotype comparisons was 'transcriptional regulation'. Distinct biologic and metabolic pathways that were altered in COX-/- mice included beta oxidation, methionine metabolism, janus kinase signaling, and GABAergic neurotransmission. Conclusion: Our findings suggest that COX-1 and COX-2 differentially modulate brain gene expression. Because certain anti-inflammatory and analgesic treatments are based on inhibition of COX activity, the specific alterations observed in this study further our understanding of the relationship of COX-1 and COX-2 with signaling pathways in brain and of the therapeutic and toxicologic consequences of COX inhibition. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NIA, Gene Express & Genom Unit, NIH, Ctr Gerontol Res, Baltimore, MD 21224 USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Rm 1S126,9 Mem Dr, Bethesda, MD 20892 USA. EM frances@mail.nih.gov OI Becker, Kevin/0000-0002-6794-6656 FU Intramural NIH HHS NR 41 TC 21 Z9 21 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 1 AR R14 DI 10.1186/gb-2007-8-1-r14 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 144UF UT WOS:000244821100010 PM 17266762 ER PT J AU Ulloa-Montoya, F Kidder, BL Pauwelyn, KA Chase, LG Luttun, A Crabbe, A Geraerts, M Sharov, AA Piao, Y Ko, MS Hu, WS Verfaillie, CM AF Ulloa-Montoya, Fernando Kidder, Benjamin L. Pauwelyn, Karen A. Chase, Lucas G. Luttun, Aernout Crabbe, Annelies Geraerts, Martine Sharov, Alexei A. Piao, Yulan Ko, Minoru Sh Hu, Wei-Shou Verfaillie, Catherine M. TI Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION PROFILES; MARROW STROMAL CELLS; BONE-MARROW; PROGENITOR CELLS; MOUSE BLASTOCYSTS; PLURIPOTENCY; MICE; PURIFICATION; ENDODERM; NANOG AB Background: Recently, several populations of postnatal stem cells, such as multipotent adult progenitor cells (MAPCs), have been described that have broader differentiation ability than classical adult stem cells. Here we compare the transcriptome of pluripotent embryonic stem cells (ESCs), MAPCs, and lineage-restricted mesenchymal stem cells (MSCs) to determine their relationship. Results: Applying principal component analysis, non-negative matrix factorization and k-means clustering algorithms to the gene-expression data, we identified a unique gene-expression profile for MAPCs. Apart from the ESC-specific transcription factor Oct4 and other ESC transcripts, some of them associated with maintaining ESC pluripotency, MAPCs also express transcripts characteristic of early endoderm and mesoderm. MAPCs do not, however, express Nanog or Sox2, two other key transcription factors involved in maintaining ESC properties. This unique molecular signature was seen irrespective of the microarray platform used and was very similar for both mouse and rat MAPCs. As MSC-like cells isolated under MAPC conditions are virtually identical to MSCs, and MSCs cultured in MAPC conditions do not upregulate MAPC-expressed transcripts, the MAPC signature is cell-type specific and not merely the result of differing culture conditions. Conclusion: Multivariate analysis techniques clustered stem cells on the basis of their expressed gene profile, and the genes determining this clustering reflected the stem cells' differentiation potential in vitro. This comparative transcriptome analysis should significantly aid the isolation and culture of MAPCs and MAPC-like cells, and form the basis for studies to gain insights into genes that confer on these cells their greater developmental potency. C1 [Ulloa-Montoya, Fernando; Kidder, Benjamin L.; Pauwelyn, Karen A.; Chase, Lucas G.; Luttun, Aernout; Verfaillie, Catherine M.] Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA. [Ulloa-Montoya, Fernando; Hu, Wei-Shou] Univ Minnesota, Dept Chem Engn & Mat Sci, Minneapolis, MN 55455 USA. [Ulloa-Montoya, Fernando; Pauwelyn, Karen A.; Luttun, Aernout; Crabbe, Annelies; Geraerts, Martine; Verfaillie, Catherine M.] Katholieke Univ Leuven, Stamcel Instituut, B-3000 Louvain, Belgium. [Sharov, Alexei A.; Piao, Yulan; Ko, Minoru Sh] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Verfaillie, CM (reprint author), Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA. EM catherine.verfaillie@med.kuleuven.be RI Ko, Minoru/B-7969-2009; OI Ko, Minoru/0000-0002-3530-3015; Verfaillie, Catherine/0000-0001-7564-4079; Luttun, Aernout/0000-0001-7902-9524 FU Intramural NIH HHS; NHLBI NIH HHS [R01-HL-69137]; NIDDK NIH HHS [R01 DK058295, R01 DK58295, U19-DK-61224-05] NR 57 TC 86 Z9 89 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 8 AR R163 DI 10.1186/gb-2007-8-8-r163 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 273NT UT WOS:000253938500015 PM 17683608 ER PT J AU Woolfe, A Elgar, G AF Woolfe, Adam Elgar, Greg TI Comparative genomics using Fugu reveals insights into regulatory subfunctionalization SO GENOME BIOLOGY LA English DT Article ID CONSERVED NONCODING ELEMENTS; RAY-FINNED FISHES; B-CELL FACTOR; VERTEBRATE EVOLUTION; SEQUENCE ALIGNMENT; DUPLICATE GENES; TELEOST FISH; MULTISPECIES CONSERVATION; PROVIDES EVIDENCE; ZEBRAFISH AB Background: A major mechanism for the preservation of gene duplicates in the genome is thought to be mediated via loss or modification of cis-regulatory subfunctions between paralogs following duplication ( a process known as regulatory subfunctionalization). Despite a number of gene expression studies that support this mechanism, no comprehensive analysis of regulatory subfunctionalization has been undertaken at the level of the distal cis-regulatory modules involved. We have exploited fish-mammal genomic alignments to identify and compare more than 800 conserved non-coding elements ( CNEs) that associate with genes that have undergone fish-specific duplication and retention. Results: Using the abundance of duplicated genes within the Fugu genome, we selected seven pairs of teleost-specific paralogs involved in early vertebrate development, each containing clusters of CNEs in their vicinity. CNEs present around each Fugu duplicated gene were identified using multiple alignments of orthologous regions between single-copy mammalian orthologs ( representing the ancestral locus) and each fish duplicated region in turn. Comparative analysis reveals a pattern of element retention and loss between paralogs indicative of subfunctionalization, the extent of which differs between duplicate pairs. In addition to complete loss of specific regulatory elements, a number of CNEs have been retained in both regions but may be responsible for more subtle levels of subfunctionalization through sequence divergence. Conclusion: Comparative analysis of conserved elements between duplicated genes provides a powerful approach for studying regulatory subfunctionalization at the level of the regulatory elements involved. C1 Univ London, Sch Biol Sci, London E1 4NS, England. NHGRI, Genom Funct Anal Sect, NIH, Rockville, MD 20870 USA. RP Woolfe, A (reprint author), Univ London, Sch Biol Sci, Mile End Rd, London E1 4NS, England. EM woolfea@mail.nih.gov OI Elgar, Greg/0000-0001-7323-1596 FU Medical Research Council [G0401138] NR 77 TC 46 Z9 50 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 4 AR R53 DI 10.1186/gb-2007-8-4-r53 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 174ZY UT WOS:000246982900012 PM 17428329 ER PT J AU Xu, X Zhan, M Duan, W Prabhu, V Brenneman, R Wood, W Firman, J Li, H Zhang, P Ibe, C Zonderman, AB Longo, DL Poosala, S Becker, KG Mattson, MP AF Xu, Xiangru Zhan, Ming Duan, Wenzhen Prabhu, Vinayakumar Brenneman, Randall Wood, William Firman, Jeff Li, Huai Zhang, Peisu Ibe, Carol Zonderman, Alan B. Longo, Dan L. Poosala, Suresh Becker, Kevin G. Mattson, Mark P. TI Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender SO GENOME BIOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; CALORIC RESTRICTION; PARKINSONS-DISEASE; HUMAN BRAIN; MICROARRAY; MICE; PROTEIN; PROFILE; TRANSCRIPTION; HIPPOCAMPUS AB Background: The structural and functional complexity of the mammalian central nervous system (CNS) is organized and modified by complicated molecular signaling processes that are poorly understood. Results: We measured transcripts of 16,896 genes in 5 CNS regions from cohorts of young, middle-aged and old male and female mice that had been maintained on either a control diet or a low energy diet known to retard aging. Each CNS region (cerebral cortex, hippocampus, striatum, cerebellum and spinal cord) possessed its own unique transcriptome fingerprint that was independent of age, gender and energy intake. Less than 10% of genes were significantly affected by age, diet or gender, with most of these changes occurring between middle and old age. The transcriptome of the spinal cord was the most responsive to age, diet and gender, while the striatal transcriptome was the least responsive. Gender and energy restriction had particularly robust influences on the hippocampal transcriptome of middle-aged mice. Prominent functional groups of age- and energy-sensitive genes were those encoding proteins involved in DNA damage responses (Werner and telomere-associated proteins), mitochondrial and proteasome functions, cell fate determination (Wnt and Notch signaling) and synaptic vesicle trafficking. Conclusion: Mouse CNS transcriptomes responded to age, energy intake and gender in a regionally distinctive manner. The systematic transcriptome dataset also provides a window into mechanisms of age-, diet- and sex-related CNS plasticity and vulnerability. C1 [Xu, Xiangru; Duan, Wenzhen; Brenneman, Randall; Zhang, Peisu; Ibe, Carol; Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. [Zhan, Ming; Prabhu, Vinayakumar; Wood, William; Firman, Jeff; Li, Huai; Zonderman, Alan B.; Poosala, Suresh; Becker, Kevin G.] NIA, Intramural Res Program, Res Resources Branch, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, Intramural Res Program, Immunol Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM MattsonM@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; OI Becker, Kevin/0000-0002-6794-6656; Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS NR 58 TC 60 Z9 60 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 11 AR R234 DI 10.1186/gb-2007-8-11-r234 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 247SQ UT WOS:000252101100008 PM 17988385 ER PT J AU Yan, B Yang, XP Lee, TL Friedman, J Tang, J Van Waes, C Chen, Z AF Yan, Bin Yang, Xinping Lee, Tin-Lap Friedman, Jay Tang, Jun Van Waes, Carter Chen, Zhong TI Genome-wide identification of novel expression signatures reveal distinct patterns and prevalence of binding motifs of p53, NF-kappaB and other signal transcription factors in head and neck squamous cell carcinoma SO GENOME BIOLOGY LA English DT Review ID PROINFLAMMATORY CYTOKINE EXPRESSION; INTERCELLULAR-ADHESION MOLECULE-1; GROWTH-FACTOR RECEPTOR; ZINC-FINGER PROTEIN; CBF-DNA COMPLEX; GENE-EXPRESSION; CONSTITUTIVE ACTIVATION; IN-VIVO; SACCHAROMYCES-CEREVISIAE; PROANGIOGENIC CYTOKINES AB Background : Differentially expressed gene profiles have previously been observed among pathologically defined cancers by microarray technologies, including head and neck squamous cell carcinomas ( HNSCC). However, the molecular expression signatures and transcriptional regulatory controls underlying the heterogeneity in HNSCC have not been well defined. Results : Genome-wide cDNA microarray profiling of ten HNSCC cell lines revealed novel gene expression signatures which distinguished cancer cell subsets associated with their p53 status. Three major clusters of overexpressed genes ( A-C) were defined through hierarchical clustering, gene ontology and statistical modeling. The promoters of genes in these clusters exhibited different patterns and prevalence of transcription factor binding sites for p53, NF-kappa B, AP-1, STAT3 and EGR1, when compared with the frequency in vertebrate promoters. Cluster A genes involved in chromatin structure and function showed enrichment for p53 and decreased AP-1 binding sites, while cluster B-C, containing cytokine and anti-apoptotic genes, showed a significant increase in prevalence of NF-kappa B binding sites. An increase in STAT3 and EGR1 binding sites was distributed among the over-expressed clusters. Novel regulatory modules containing p53 or NF-kappa B concomitant with other transcription factor binding motifs were identified, and experimental data supported the predicted transcriptional regulation and binding activity. Conclusion : Transcription factors p53, NF-kappa B, and AP-1 may be important determinants of the heterogeneous pattern of gene expression, while STAT3 and EGR1 may broadly enhance gene expression. Defining these novel gene signatures and regulatory mechanisms will be important for establishing new molecular classifications and sub-typing for development of targeted therapeutics for HNSCC. C1 NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. NIDCD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA. RP Chen, Z (reprint author), NIDCD, Head & Neck Surg Branch, NIH, 10 Ctr Dr,10-5D55,MSC-1419, Bethesda, MD 20892 USA. EM yanbi@nidcd.nih.gov; yangxg@nidcd.nih.gov; leetl@mail.nih.gov; friedmanj@nidcd.nih.gov; jtang@utmem.edu; vanwaesc@nidcd.nih.gov; chenz@nidcd.nih.gov RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 FU NIDCD NIH HHS [Z01 DC000016] NR 116 TC 37 Z9 37 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2007 VL 8 IS 5 AR r78 DI 10.1186/gb-2007-8-5-r78 PG 55 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 175AA UT WOS:000246983100013 PM 17498291 ER PT J AU Roh, TY Wei, G Farrell, CM Zhao, K AF Roh, Tae-young Wei, Gang Farrell, Catherine M. Zhao, Keji TI Genome-wide prediction of conserved and nonconserved enhancers by histone acetylation patterns SO GENOME RESEARCH LA English DT Article ID BETA-GLOBIN LOCUS; SPECIES SEQUENCE COMPARISONS; REGULATORY ELEMENTS; V(D)J RECOMBINATION; CHROMATIN-STRUCTURE; FUGU-RUBRIPES; DNA; CELLS; METHYLATION; MOUSE AB Comparative genomic studies have been useful in identifying transcriptional regulatory elements in higher eukaryotic genomes, but many important regulatory elements cannot be detected by such analyses due to evolutionary variations and alignment tool limitations. Therefore, in this study we exploit the highly conserved nature of epigenetic modifications to identify potential transcriptional enhancers. By using a high-resolution genome-wide mapping technique, which combines the chromatin immunoprecipitation and serial analysis of gene expression assays, we have recently determined the distribution of lysine 9/14-diacetylated histone H3 in human T cells. We showed the existence of 46,813 regions with clusters of histone acetylation, termed histone acetylation islands, some of which correspond to known transcriptional regulatory elements. In the present study, we find that 4679 sequences conserved between human and pufferfish coincide with histone acetylation islands, and random sampling shows that 33% (13/39) of these can function as transcriptional enhancers in human Jurkat T cells. In addition, by comparing the human histone acetylation island sequences with mouse genome sequences, we find that despite the conservation of many of these regions between these species, 21,855 of these sequences are not conserved. Furthermore, we demonstrate that about 50% (26/51) of these nonconserved sequences have enhancer activity in Jurkat cells, and that many of the orthologous mouse sequences also have enhancer activity in addition to conserved epigenetic modification patterns in mouse T-cell chromatin. Therefore, by combining epigenetic modification and sequence data, we have established a novel genome-wide method for identifying regulatory elements not discernable by comparative genomics alone. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Zhao, K (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov RI Wei, Gang/A-3291-2011 FU Intramural NIH HHS NR 49 TC 87 Z9 89 U1 1 U2 5 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 JAN PY 2007 VL 17 IS 1 BP 74 EP 81 DI 10.1101/gr.5767907 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 121XX UT WOS:000243191400010 PM 17135569 ER PT J AU Sun, Y Li, H Liu, Y Shin, S Mattson, MP Rao, MS Zhan, M AF Sun, Yu Li, Huai Liu, Ying Shin, Soojung Mattson, Mark P. Rao, Mahendra S. Zhan, Ming TI Cross-species transcriptional profiles establish a functional portrait of embryonic stem cells SO GENOMICS LA English DT Article DE embryonic stem cell; embryonic bodies; comparative transcriptomics; functional genomics; LIF; FGF; nodal; Wnt; BMP; TGF-beta ID GENE-EXPRESSION SIGNATURES; SELF-RENEWAL; MOLECULAR SIGNATURE; CARCINOMA-CELLS; NEURONAL DIFFERENTIATION; HUMAN BLASTOCYSTS; MOUSE EMBRYOS; IN-VITRO; LINES; PATHWAY AB An understanding of the regulatory mechanisms responsible for pluripotency in embryonic stem cells (ESCs) is critical for realizing their potential in medicine and science. Significant similarities exist among ESCs harvested from different species, yet major differences have also been observed. Here, by cross-species analysis of a large set of functional categories and all transcription factors and growth factors, we reveal conserved and divergent functional landscapes underlining fundamental and species-specific mechanisms that regulate ESC development. Global transcriptional trends derived from all expressed genes, instead of differentially expressed genes alone, were examined, allowing for a higher discriminating power in the functional portrait. We demonstrate that cross-species correlation of transcriptional changes that occur upon ESC differentiation is a powerful predictor of ESC-important biological pathways and functional cores within a pathway. Hundreds of functional modules, as defined by Gene Ontology, were associated with conserved expression patterns but bear no overt relationship to ESC development, suggestive of new mechanisms critical to ESC pluripotency. Yet other functional modules were not conserved; instead, they were significantly upregulated in ESCs of either species, suggestive of species-specific regulation. The comparisons of ESCs across species and between human ESCs and embryonal carcinoma stem cells suggest that while pluripotency as an essential function in multicellular organisms is conserved throughout evolution, mechanisms primed for differentiation are less conserved and contribute substantially to the differences among stem cells derived from different tissues or species. Our findings establish a basis for defining the "stemness" properties of ESCs from the perspective of functional conservation and variation. The data and analyses resulting from this study provide a framework for new hypotheses and research directions and a public resource for functional genomics of ESCs. Published by Elsevier Inc. C1 NIA, NIH, Bioinformat Unit, Res Resources Branch, Baltimore, MD 21224 USA. CRL, Invitrogen Corp, Carlsbad, CA 92008 USA. NIA, NIH, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Neurosci Program, Baltimore, MD 21224 USA. RP Rao, MS (reprint author), NIA, NIH, Bioinformat Unit, Res Resources Branch, 333 Cassall Dr, Baltimore, MD 21224 USA. EM rao@invitrogen.com; zhanmi@mail.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000619-01] NR 73 TC 22 Z9 25 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 0888-7543 J9 GENOMICS JI Genomics PD JAN PY 2007 VL 89 IS 1 BP 22 EP 35 DI 10.1016/j.ygeno.2006.09.010 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 123NK UT WOS:000243302400003 PM 17055697 ER PT J AU Goh, G Raudsepp, T Durkin, K Wagner, ML Schaffer, AA Agarwala, R Tozaki, T Mickelson, JR Chowdhary, BP AF Goh, Glenda Raudsepp, Terje Durkin, Keith Wagner, Michelle L. Schaffer, Alejandro A. Agarwala, Richa Tozaki, Teruaki Mickelson, James R. Chowdhary, Bhanu P. TI High-resolution gene maps of horse chromosomes 14 and 21: Additional insights into evolution and rearrangements of HSA5 homologs in mammals SO GENOMICS LA English DT Article DE horse; ECA14; ECA21; HSA5; gene mapping; radiation hybrid map; FISH; comparative map; chromosome evolution ID EQUINE MICROSATELLITE LOCI; RADIATION HYBRID MAP; COMPARATIVE GENOME MAPS; ZOO-FISH; ANCESTRAL KARYOTYPE; LINKAGE MAP; CYTOGENETIC LOCALIZATION; EUTHERIAN MAMMALS; RH MAP; SEGMENTS AB High-resolution physically ordered gene maps for equine homologs of human chromosome 5 (HSA5), viz., horse chromosomes 14 and 21 (ECA14 and ECA21), were generated by adding 179 new loci (131 gene-specific and 48 micro satellites) to the existing maps of the two chromosomes. The loci were mapped primarily by genotyping on a 5000-rad horse x hamster radiation hybrid panel, of which 28 were mapped by fluorescence in situ hybridization. The approximately fivefold increase in the number of mapped markers on the two chromosomes improves the average resolution of the map to 1 marker/0.9 Mb. The improved resolution is vital for rapid chromosomal localization of traits of interest on these chromosomes and for facilitating candidate gene searches. The comparative gene mapping data on ECA14 and ECA21 finely align the chromosomes to sequence/gene maps of a range of evolutionarily distantly related species. It also demonstrates that compared to ECA14, the ECA21 segment corresponding to HSA5 is a more conserved region because of preserved gene order in a larger number of and more diverse species. Further, comparison of ECA14 and the distal three-quarters region of ECA21 with corresponding chromosomal segments in 50 species belonging to 11 mammalian orders provides a broad overview of the evolution of these segments in individual orders from the putative ancestral chromosomal configuration. Of particular interest is the identification and precise demarcation of equid/Perissodactyl-specific features that for the first time clearly distinguish the origins of ECA14 and ECA21 from similar-looking status in the Cetartiodactyls. (c) 2006 Elsevier Inc. All rights reserved. C1 Texas A&M Univ, Dept Vet Integrat Biosci, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. Univ Minnesota, Dept Vet Biosci, St Paul, MN 55108 USA. NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. Mol Genet Sect, Lab Racing Chem, Tochigi 3200851, Japan. Texas A&M Univ, Dept Anim Sci, Coll Agr & Life Sci, College Stn, TX 77843 USA. RP Chowdhary, BP (reprint author), Texas A&M Univ, Dept Vet Integrat Biosci, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. EM bchowdhary@cvm.tamu.edu RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS NR 53 TC 7 Z9 7 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN PY 2007 VL 89 IS 1 BP 89 EP 112 DI 10.1016/j.ygeno.2006.06.012 PG 24 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 123NK UT WOS:000243302400009 PM 16916595 ER PT J AU Keebaugh, AC Sullivan, RT Thomas, JW AF Keebaugh, Alaine C. Sullivan, Robert T. Thomas, James W. CA NISC Compartive Sequencing Program TI Gene duplication and inactivation in the HPRT gene family SO GENOMICS LA English DT Article DE comparative genomics; gene structure; genome evolution; HPRT1; PRTFDC1; HPRT1L; gene inactivation ID PHYLOGENETIC ANALYSIS; VERTEBRATE EVOLUTION; MAXIMUM-LIKELIHOOD; GENOME SEQUENCE; COMMON VARIANT; AMP DEAMINASE; ALIGNMENTS; DEFICIENCY; PROTEINS; ORIGIN AB Hypoxanthine phosphoribosyltransferase (HPRT1) is a key enzyme in the purine salvage pathway, and mutations in HPRT1 cause Lesch-Nyhan disease. The studies described here utilized targeted comparative mapping and sequencing, in conjunction with database searches, to assemble a collection of 53 HPRT1 homologs from 28 vertebrates. Phylogenetic analysis of these homologs revealed that the HPRT gene family expanded as the result of ancient vertebrate-specific duplications and is composed of three groups consisting of HPRT1, phosphoribosyl transferase domain containing protein 1 (PRTFDC1), and HPRT1L genes. All members of the vertebrate HPRT gene family share a common intron-exon structure; however, we have found that the three gene groups have distinct rates of evolution and potentially divergent functions. Finally, we report our finding that PRTFDC1 was recently inactivated in the mouse lineage and propose the loss of function of this gene as a candidate genetic basis for the phenotypic disparity between HPRT-deficient humans and mice. (c) 2006 Elsevier Inc. All rights reserved. C1 Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. Emory Univ, Program Populat Biol Ecol & Evolut, Atlanta, GA 30322 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH Intramural Sequencing Ctr, Bethesda, MD 20892 USA. RP Thomas, JW (reprint author), Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. EM jthomas@genetics.emory.edu FU NIAID NIH HHS [T32AI055404]; NIMH NIH HHS [U01MH068185] NR 50 TC 9 Z9 10 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN PY 2007 VL 89 IS 1 BP 134 EP 142 DI 10.1016/j.ygeno.2006.07.003 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 123NK UT WOS:000243302400012 PM 16928426 ER PT S AU Vadyvaloo, V Jarrett, C Sturdevant, D Sebbane, F Hinnebusch, BJ AF Vadyvaloo, Viveka Jarrett, Clayton Sturdevant, Daniel Sebbane, Florent Hinnebusch, B. Joseph BE Perry, RD Fetherston, JD TI Analysis of Yersinia pestis gene expression in the flea vector SO GENUS YERSINIA: FROM GENOMICS TO FUNCTION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 9th International Symposium on Yersinia CY OCT 10-14, 2006 CL Lexington, KY ID CAENORHABDITIS-ELEGANS; ESCHERICHIA-COLI; BIOFILM; POLYAMINES; PLAGUE; PUTRESCINE; PHENOTYPE; GROWTH; IDENTIFICATION; PIGMENTATION AB Yersinia pestis is the causative agent of plague. Unlike the other pathogenic Yersinia species, Y. pestis has evolved an arthropod-borne route of transmission, alternately infecting flea and mammalian hosts. Distinct subsets of genes are hypothesized to be differentially expressed during infection of the arthropod vector and mammalian host. Genes crucial for mammalian infection are referred to as virulence factors whilst genes playing a role in the flea vector are termed transmission factors. This article serves as a review of known factors involved in flea-borne transmission and introduces an 'in vivo' microarray approach to elucidating the genetic basis of Y. pestis infection of- and transmission by the flea. C1 [Vadyvaloo, Viveka; Jarrett, Clayton; Hinnebusch, B. Joseph] NIH, Lab Zoonot Pathogens, Bethesda, MD 20892 USA. RP Vadyvaloo, V (reprint author), NIH, Lab Zoonot Pathogens, Bethesda, MD 20892 USA. EM vadyvaloov@niaid.nih.gov RI Sebbane, Florent/D-4213-2009 NR 31 TC 10 Z9 10 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-72123-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 603 BP 192 EP 200 PG 9 WC Medicine, Research & Experimental; Microbiology SC Research & Experimental Medicine; Microbiology GA BGV89 UT WOS:000250831600016 PM 17966415 ER PT J AU Everhart, JE Podskalny, JM AF Everhart, James E. Podskalny, Judith M. BE Talley, NJ Locke, GR Saito, YA TI Funding Opportunities at the National Institutes of Health SO GI EPIDEMIOLOGY LA English DT Article; Book Chapter C1 [Everhart, James E.] NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Podskalny, Judith M.] NIDDK, Res Fellowship & Career Dev Program, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. [Podskalny, Judith M.] NIDDK, Digest Dis Ctr Program, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. RP Everhart, JE (reprint author), NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-69218-9 PY 2007 BP 109 EP 114 DI 10.1002/9780470692189.ch16 D2 10.1002/9780470692189 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BCJ73 UT WOS:000310305700018 ER PT J AU Cheng, XF MacVittie, T Meisenberg, B Welty, E Farese, A Tadaki, D Takebe, N AF Cheng, Xiangfei MacVittie, Thomas Meisenberg, Barry Welty, Emily Farese, Ann Tadaki, Douglas Takebe, Naoko TI Human brain endothelial cells (HUBEC) promote SCID repopulating cell expansion through direct contact SO GROWTH FACTORS LA English DT Article DE contact culture; CD34+/CD38-; cord blood CD34+cells; Wnt/beta-catenin ID HEMATOPOIETIC STEM-CELLS; HUMAN BONE-MARROW; EX-VIVO CULTURE; WNT GENE FAMILY; PROGENITOR CELLS; IN-VITRO; MOLECULAR-CLONING; GROWTH-FACTORS; STROMAL CELLS; DIFFERENTIATION AB The objective of this study was to re-evaluate the previously published hematopoietic stem cell (HSC) expansion work using human brain endothelial cells (HUBEC). The expansion effect of contact and non-contact conditions was reported to be equivalent by others. However, we report here different results that the expansion can be achieved only with direct contact. We co-cultured human CD34 + cells with and without HUBEC contact for seven days with cytokines and the readouts were CD34+/CD38 2 phenotype and SCID repopulating cell (SRC) frequency. Also tested was the inhibitory effect of Wnt receptor inhibitor Dkk-1 on HUBEC contact ex vivo expansion; whether an increased expression of Wnt3 occurs on the HUBEC surface; and detection of an increased nuclear localization of beta-catenin in CD34+/CD38 2 cells in HUBEC contact culture condition. We conclude that the successful expansion by HUBEC contact culture is a candidate explanation based on the Wnt family protein, possibly Wnt3, expression on HUBEC. C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Natl Med Res Ctr, Silver Spring, MD 20910 USA. RP Takebe, N (reprint author), NCI, Div Canc Therapy & Diagnos, Canc Therapy Evaluat Program, IDB Branch, 6130 Executive Blvd,EPN 7131, Bethesda, MD 20892 USA. EM takeben@gmail.com NR 28 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PY 2007 VL 25 IS 3 BP 141 EP 150 DI 10.1080/08977190701671662 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 236CU UT WOS:000251281400001 PM 18049950 ER PT J AU Booth, BW Smith, GH AF Booth, Brian W. Smith, Gilbert H. TI Roles of transforming growth factor-alpha in mammary development and disease SO GROWTH FACTORS LA English DT Article DE TGF alpha; mammary; development; cancer ID AIRWAY EPITHELIAL-CELLS; METASTATIC BREAST-CANCER; TGF-ALPHA; FACTOR RECEPTOR; TRANSGENIC MICE; EGF RECEPTOR; CONVERTING-ENZYME; MESSENGER-RNA; COLORECTAL-CANCER; ERBB RECEPTORS AB Transforming growth factor-alpha (TGF alpha) is a member of the epidermal growth factor (EGF) family. Expression of TGFa is highly regulated in response to exogenous cellular signals including cytokines and other growth factors. The growth factor has been found to be indispensable for proper development of many tissues and organs. TGFa has also been implicated in numerous disease states including forms of breast cancer. This minireview summarizes the basic biology of TGFa and its actions during normal and pathogenic development of the mammary epithelium. C1 [Booth, Brian W.; Smith, Gilbert H.] NCI, NIH, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, NIH, Mammary Biol & Tumorigenesis Lab, 37 Convent Dr,Bldg 37,Room 1112B, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 95 TC 18 Z9 20 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PY 2007 VL 25 IS 4 BP 227 EP 235 DI 10.1080/08977190701750698 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 242UI UT WOS:000251751300002 PM 18092231 ER PT B AU Bachrach, C AF Bachrach, Christine BE Hofferth, SL Casper, LM TI Taking stock: Do surveys of men's fertility deliver? SO Handbook of Measurement Issues in Family Research LA English DT Proceedings Paper CT Conference on Measurement Issues in Family Demography CY NOV, 2003 CL Bethesda, MD C1 Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-5617-X PY 2007 BP 325 EP 332 PG 8 WC Family Studies SC Family Studies GA BER28 UT WOS:000239025200019 ER PT S AU Bungay, PM Morrison, PF Dedrick, RL Chefer, VI Zapata, A AF Bungay, Peter M. Morrison, Paul F. Dedrick, Robert L. Chefer, Vladimir I. Zapata, Agustin BE Westerink, BHC Cremers, TIFH TI Principles of quantitative microdialysis SO HANDBOOK OF MICRODIALYSIS: METHODS, APPLICATIONS AND PERSPECTIVES SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter ID IN-VIVO MICRODIALYSIS; ZERO-NET-FLUX; INTERNAL REFERENCE TECHNIQUE; DUAL-PROBE MICRODIALYSIS; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; RAT STRIATUM; EXTRACTION FRACTION; SKELETAL-MUSCLE; BLOOD-FLOW AB In vivo microdialysis relies principally on diffusion as the mechanism for solute exchange between the tissue and the probe perfusate. Mathematical models for describing microdialysis have been formulated based on known concepts of diffusion through tissue and the membranes with which probes are currently constructed. The models predict that the rate of exchange is strongly influenced by processes that remove the analyte from the tissue interstitium. This presents an opportunity to derive additional information about the clearance processes from microdialysis measurements. Experimental and mathematical approaches that have been developed to date for exploiting this possibility are presented in a revised framework suitable for both hydrophilic and lipophilic analytes. C1 [Bungay, Peter M.; Morrison, Paul F.; Dedrick, Robert L.] NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. [Chefer, Vladimir I.; Zapata, Agustin] NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, NIH, Baltimore, MD USA. RP Bungay, PM (reprint author), NIH, Div Bioengn & Phys Sci, Bldg 10, Bethesda, MD 20892 USA. EM bungayp@mail.nih.gov NR 105 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-046966-9 J9 HBK BEHAV NEUROSCI PY 2007 VL 16 BP 131 EP 167 DI 10.1016/S1569-7339(06)16008-7 PG 37 WC Medicine, Research & Experimental; Neurosciences SC Research & Experimental Medicine; Neurosciences & Neurology GA BCQ67 UT WOS:000311036100009 ER PT J AU Kaltsas, GA Chrousos, GP AF Kaltsas, Gregory A. Chrousos, George P. BE Cacioppo, JT Tassinary, LG Berntson, GG TI The Neuroendocrinology of Stress SO HANDBOOK OF PSYCHOPHYSIOLOGY, 3RD EDITION LA English DT Article; Book Chapter ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; SEXUALLY-ABUSED GIRLS; CUSHINGS-SYNDROME; NEUROPEPTIDE-Y; INTERLEUKIN-6 SECRETION; RHEUMATOID-ARTHRITIS; ARGININE-VASOPRESSIN; NERVOUS-SYSTEM; LEWIS RATS C1 [Kaltsas, Gregory A.] Univ Athens, GR-10679 Athens, Greece. [Chrousos, George P.] NICHD, PREB, NIH, Bethesda, MD 20892 USA. RP Kaltsas, GA (reprint author), Univ Athens, GR-10679 Athens, Greece. NR 59 TC 24 Z9 24 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-84471-0 PY 2007 BP 303 EP 318 D2 10.2277/ 0521844711 PG 16 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA BXS75 UT WOS:000296960500013 ER PT J AU Apostoli, P Telisman, S Sager, PR AF Apostoli, Pietro Telisman, Spomenka Sager, Polly R. BE Nordberg, GF Fowler, BA Nordberg, M Friberg, LT TI Reproductive and Developmental Toxicity of Metals SO HANDBOOK ON THE TOXICOLOGY OF METALS, 3RD EDITION LA English DT Article; Book Chapter ID OCCUPATIONAL LEAD-EXPOSURE; IN-UTERO EXPOSURE; THIMEROSAL-CONTAINING VACCINES; PRENATAL METHYLMERCURY EXPOSURE; HEXAVALENT CHROMIUM COMPOUNDS; TESTICULAR ENDOCRINE FUNCTION; SEYCHELLES CHILD-DEVELOPMENT; MACACA-FASCICULARIS INFANTS; VISUAL RECOGNITION MEMORY; DEVELOPING NERVOUS-SYSTEM AB Metals exert a wide variety of adverse effects on reproduction and development including influence on fertility, intrauterine growth retardation, abortions, malformations, birth defects, and developmental effects, mainly those on the nervous system. Metals may affect reproduction or development directly, at relatively low doses, or indirectly through systemic toxicity, generally at higher doses. More recent, important mechanisms of action are those related to endocrine disruption and oxidative stress. The effects produced by metals depend on several factors, such as the timing and duration of exposure, their distribution and accumulation in various organs (e.g., the nervous system), and on the ability to interfere with specific developmental processes. Interesting interactions between environmental and congenital factors have been documented; genetic polymorphisms can affect fetal susceptibility to teratogens or maternal ability to detoxify and excrete xenobiotics. Male reproductive effects of high doses of many metals have been observed in animals, whereas there is still insufficient evidence to the human male concerning a quantitative dose-response relationship. This could be partly explained by considerable interspecies differences in susceptibility to reproductive toxicity and in the route, level, and duration of metal exposure. Human studies have provided substantial evidence of effects for only a few metals. These include lead-induced effects on male fertility and certain parameters of semen quality, even at moderate exposure levels, effects by cadmium on prostate impairment and serum testosterone, and less well-documented male reproductive effects of mercury, manganese, chromium, nickel, and arsenic at levels significantly lower than those that cause systemic toxicity. The effects of metals on female reproduction may arise from their action on several stages beginning in fetal life, during early development or maturity, and include manifestations such as subfertility, infertility, intrauterine growth retardation, spontaneous abortions, malformations, birth defects, postnatal death, learning and behavior deficits, and premature aging; evidence is usually limited to animal data or studies on fertility and spontaneous abortions The clinical and epidemiological findings related to metal-induced effects on female reproduction are often difficult to interpret, because many other factors may influence the outcome such as age, ovarian reserve, hormonal imbalance, behavior, genetics, male fertility factors, and sexually transmitted diseases. Exposure to metals during organogenesis may cause fetal anomalies, whereas exposure during other periods of development may result in embryo or fetal lethality or other developmental effects. Teratogenesis bioassays in rodents (hamsters, mice, or rats) have yielded positive results for the compounds of many metals (Al, As, Bo, Cd, Co, Cr, Cu, Ga, Hg, Li, Mn, Ni, Pb, Se, U, V, and Zn), producing fetal and early postnatal deaths, as well as malformations such as anencephaly, eye defects, cleft palate, and skeletal anomalies. The relevance of these findings to human exposure is, however, still unclear. Neonatal and early postnatal periods are lifespan segments during which sensitivity to metals is high, and lead toxicity on the developing organism represents an illustrative example for related problems and questions. In the last decade, children's blood lead (PbB) levels have declined significantly in a number of countries, and current prevalent mean levels in developed countries are <50 mu g/L. Despite this reduction, childhood lead poisoning continues to be a public health problem for certain high-risk groups. Recent studies have extended the association of blood lead and intellectual impairment to PbB levels <100 mu g/L and now challenge the safety of this level that for more than a decade has served as a community alert level for preventive action. The recent studies cast doubt whether a toxicological threshold and no-effect value exists for lead-related developmental toxicity. This chapter focuses on the reproductive and developmental effects by metals of traditional interest for toxicologists, such as lead, mercury, and cadmium, but also provides information, where available, on chromium, arsenic, manganese, and nickel, and on metals of more recent interest such as aluminum, platinum, vanadium, lithium, and uranium. C1 [Apostoli, Pietro] Univ Brescia, Inst Occupat Hlth & Ind Hyg, I-25123 Brescia, Italy. [Telisman, Spomenka] Univ Zagreb, Inst Med Res & Occupat Hlth, Zagreb 41001, Croatia. [Sager, Polly R.] NIAID, Off Biodef Res Affairs, NIH, Bethesda, MD 20892 USA. RP Apostoli, P (reprint author), Univ Brescia, Inst Occupat Hlth & Ind Hyg, I-25123 Brescia, Italy. NR 549 TC 10 Z9 10 U1 1 U2 18 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054610-0 PY 2007 BP 213 EP 249 DI 10.1016/B978-012369413-3/50067-7 PG 37 WC Toxicology SC Toxicology GA BCS56 UT WOS:000311285300014 ER PT B AU Saenz, R Rubio, M AF Saenz, Rogelio Rubio, Mercedes BA Angel, JL Whitfield, KE BF Angel, JL Whitfield, KE TI Lack of Health Insurance Coverage and Mortality Among Latino Elderly in the United States SO HEALTH OF AGING HISPANICS: THE MEXICAN-ORIGIN POPULATION LA English DT Article; Book Chapter ID OLDER MEXICAN-AMERICANS; DISABLEMENT PROCESS; ETHNIC-DIFFERENCES; HHANES 1982-84; MEDICAL-CARE; ACCESS; POPULATION; ADULTS; DISABILITY; HISPANICS C1 [Saenz, Rogelio] Texas A&M Univ, Dept Sociol, College Stn, TX 77843 USA. [Rubio, Mercedes] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Saenz, R (reprint author), Texas A&M Univ, Dept Sociol, College Stn, TX 77843 USA. NR 34 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-47208-9; 978-0-387-47206-5 PY 2007 BP 181 EP 194 DI 10.1007/978-0-387-47208-9_13 D2 10.1007/978-0-387-47208-9 PG 14 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA BKN41 UT WOS:000268685800014 ER PT S AU Le Couteur, DG Cogger, VC McCuskey, RS De Cabo, R Smedsrod, B Sorensen, KK Warren, A Fraser, R AF Le Couteur, David G. Cogger, Victoria C. McCuskey, Robert S. De Cabo, Rafael Smedsrod, Bard Sorensen, Karen K. Warren, Alessandra Fraser, Robin BE Weller, NJ Rattan, SIS TI Age-related changes in the liver sinusoidal endothelium - A mechanism for dyslipidemia SO HEALTHY AGING AND LONGEVITY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Healthy Aging and Longevity CY OCT 13-15, 2006 CL Melbourne, AUSTRALIA DE liver; aging; liver sinusoidal endothelial cell; chylomicron remnant; endocytosis; caloric restriction ID CALORIC RESTRICTION; DRUG CLEARANCE; AGING LIVER; RAT-LIVER; PSEUDOCAPILLARIZATION; ATHEROSCLEROSIS; CELLS; LIPOPROTEINS; CIRRHOSIS; METABOLISM AB The liver sinusoidal endothelial cell (LSEC) influences the transfer of substrates between the sinusoidal blood and hepatocytes and has a major role in endocytosis; therefore, changes in the LSEC have significant implications for hepatic function. There are major morphological changes in the LSEC in old age called pseudocapillarization. These changes include increased LSEC thickness and reduced numbers of pores in the LSEC, which are called fenestrations. Pseudocapillarization has been found in old humans, rats, mice, and nonhuman primates. In addition, old age is associated with impaired LSEC endocytosis and increased leukocyte adhesion, which contributes to reduced hepatic perfusion. Given that fenestrations in the endothelium allow passage of some lipoproteins, including chylomicron remnants, age-related reduction in fenestrations impairs hepatic lipoprotein metabolism. In old rats, caloric restriction was associated with complete preservation of LSEC morphology find fenestrations. In conclusion, pseudocapillarization of the LSEC is a newly discovered aging change that, through its effects on lipoproteins, contributes to the association between old age, dyslipidemia, and vascular disease. C1 [Le Couteur, David G.; Cogger, Victoria C.; Warren, Alessandra] Univ Sydney, Ctr Educ & Res Ageing, Sydney, NSW 2139, Australia. [Le Couteur, David G.; Cogger, Victoria C.; Warren, Alessandra] Concord RG Hosp, Sydney, NSW 2139, Australia. [McCuskey, Robert S.] Univ Arizona, Coll Med, Dept Anat & Cell Biol, Tucson, AZ USA. [McCuskey, Robert S.; Smedsrod, Bard; Sorensen, Karen K.] Univ Tromso, Inst Med Biol, Dept Cell Biol & Histol, Tromso, Norway. [De Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Fraser, Robin] Univ Otago, Christchurch Sch Med, Christchurch, New Zealand. RP Le Couteur, DG (reprint author), Univ Sydney, Ctr Educ & Res Ageing, Sydney, NSW 2139, Australia. EM dlecouteur@med.usyd.edu.au RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU NIA NIH HHS [R21 AG-02582] NR 40 TC 15 Z9 16 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-680-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1114 BP 79 EP 87 DI 10.1196/annals.1396.003 PG 9 WC Geriatrics & Gerontology; Multidisciplinary Sciences; Physiology SC Geriatrics & Gerontology; Science & Technology - Other Topics; Physiology GA BHA05 UT WOS:000251775900010 PM 17804522 ER PT J AU Dravis, C Wu, T Chumley, MJ Yokoyama, N Wei, SN Wu, DK Marcus, DC Henkemeyer, M AF Dravis, Christopher Wu, Tao Chumley, Michael J. Yokoyama, Nobuhiko Wei, Shiniu Wu, Doris K. Marcus, Daniel C. Henkemeyer, Mark TI EphB2 and ephrin-B2 regulate the ionic homeostasis of vestibular endolymph SO HEARING RESEARCH LA English DT Article DE Ephrin-B2; EphB2; receptor tyrosine kinase; vestibular epithelium; dark cells; transitional cells; endolymph; potassium; ionic homeostasis ID RECEPTOR TYROSINE KINASE; CRYSTAL-STRUCTURE; STRIA VASCULARIS; DARK CELLS; INNER-EAR; AUTOPHOSPHORYLATION SITE; TRANSEPITHELIAL VOLTAGE; TRANSMEMBRANE LIGANDS; TRANSPORT MECHANISMS; COMMISSURAL AXONS AB The ability to transport cations and anions across epithelia is critical for the regulation of pH, ionic homeostasis, and volume of extracellular fluids. Although the transporters and channels that facilitate ion and water movement across cell membranes are well known, the molecular mechanisms and signal transduction events that regulate these activities remain poorly understood. The Eph family of receptor tyrosine kinases and their membrane-anchored ephrin ligands are well known to transduce bidirectional signals that control axon guidance and other cell migration/adhesion events during development. However, these molecules are also expressed in non-motile epithelial cells, including EphB2 in K+-secreting vestibular dark cells and ephrin-B2 in the adjacent transitional cells of the inner ear. Consistent with these expression patterns, mice with cytoplasmic domain mutations that interfere with EphB2 forward signaling or ephrin-B2 reverse signaling exhibit a hyperactive circling (waltzing) locomotion associated with a decreased amount of endolymph fluid that normally fills the vestibular labyrinth. Endolymph is unusual as an extracellular fluid in that it is normally high in K+ and low in Na+. Direct measurement of this fluid in live animals revealed significant decreases in K+ concentration and endolymphatic potential in both EphB2 and ephrin-B2 mutant mice. Our findings provide evidence that bidirectional signaling mediated by B-subclass Ephs and ephrins controls the production and ionic homeostasis of endolymph fluid and thereby provide the first evidence that these molecules can control the activities of mature epithelial cells. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Texas, SW Med Ctr, Ctr Dev Biol, Dallas, TX 75390 USA. Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA. Natl Inst Deafness & Commun Disorders, Mol Biol Lab, Rockville, MD 20850 USA. RP Henkemeyer, M (reprint author), Univ Texas, SW Med Ctr, Ctr Dev Biol, Dallas, TX 75390 USA. EM mark.henkemeyer@utsouthwestern.edu FU NIDCD NIH HHS [R01 DC00212, R01 DC006225]; NIGMS NIH HHS [T32 GM08203] NR 67 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JAN PY 2007 VL 223 IS 1-2 BP 93 EP 104 DI 10.1016/j.heares.2006.10.007 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 132LO UT WOS:000243944500009 PM 17158005 ER PT J AU Nguyen, LN Furuya, MH Wolfraim, LA Nguyen, AP Holdren, MS Campbell, JS Knight, B Yeoh, GCT Fausto, N Parks, WT AF Nguyen, Lananh N. Furuya, Momoko H. Wolfraim, Lawrence A. Nguyen, Anthony P. Holdren, Matthew S. Campbell, Jean S. Knight, Belinda Yeoh, George C. T. Fausto, Nelson Parks, W. Tony TI Transforming growth factor-beta differentially regulates oval cell and hepatocyte proliferation SO HEPATOLOGY LA English DT Article ID LIVER-REGENERATION; INTERFERON-GAMMA; RAT HEPATOCYTES; DNA-SYNTHESIS; CULTURE; MECHANISM; APOPTOSIS; CYTOKINES; PATHWAYS AB Oval cells are hepatocytic precursors that proliferate in late-stage cirrhosis and that give rise to a subset of human hepatocellular carcinomas. Although liver regeneration typically occurs through replication of existing hepatocytes, oval cells proliferate only when hepatocyte proliferation is inhibited. Transforming growth factor-beta (TGF-beta) is a key inhibitory cytokine for hepatocytes, both in vitro and in vivo. Because TGF-beta levels are elevated in chronic liver injury when oval cells arise, we hypothesized that oval cells may be less responsive to the growth inhibitory effects of this cytokine. To examine TGF-beta signaling in vivo in oval cells arise, we analyzed livers of rats fed a choline-deficient, ethionine-supplemented (CDE) diet for phospho-Smad2. Phospho-Smad2 was detected in more than 80% of hepatocytes, but staining was substantially reduced in oval cells. Ki67 staining, in contrast, was significantly more common in oval cells than hepatocytes. To understand the inverse relationship between TGF-beta signaling and proliferation in oval cells and hepatocytes, we examined TGF-beta signaling in vitro. TGF-beta caused marked growth inhibition in primary hepatocytes and the AML12 hepatocyte cell line. Two oval cell lines, LE/2 and LE/6, were less responsive. The greater sensitivity of the hepatocytes to TGF-beta-induced growth inhibition may result from the absence of Smad6 in these cells. Conclusion: Our results indicate that oval cells, both in vivo and in vitro, are less sensitive to TGF-beta-induced growth inhibition than hepatocytes. These findings further suggest an underlying mechanism for the proliferation of oval cells in an environment inhibitory to hepatocytic proliferation. C1 Univ Washington, Dept Pathol, Seattle, WA 98195 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Univ Western Australia, Western Australian Inst Med Res, Med Res Ctr, Nedlands, WA 6009, Australia. RP Parks, WT (reprint author), Univ Washington, Dept Pathol, HSB E506,Box 357470, Seattle, WA 98195 USA. EM parkst@u.washington.edu RI Yeoh, George/B-5339-2011; OI Yeoh, George/0000-0002-4740-4702; Parks, W. Tony/0000-0001-7341-3277 NR 29 TC 94 Z9 102 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2007 VL 45 IS 1 BP 31 EP 41 DI 10.1002/hep.21466 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 122DY UT WOS:000243207100007 PM 17187411 ER PT J AU Conjeevaram, HS Kleiner, DE Everhart, JE Hoofnagle, JH Zacks, S Afdhal, NH Wahed, AS AF Conjeevaram, Hari S. Kleiner, David E. Everhart, Jay E. Hoofnagle, Jay H. Zacks, Steven Afdhal, Nezam H. Wahed, Abdus S. CA Virahep-C Study Grp TI Race, insulin resistance and hepatic steatosis in chronic hepatitis C SO HEPATOLOGY LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; VIRUS; DISEASE; PEGINTERFERON; PROGRESSION; PREVALENCE; GENOTYPE-1; MECHANISMS; INFECTION; RIBAVIRIN AB Hepatic steatosis is common in chronic hepatitis C and has been linked to concurrent obesity, insulin resistance, diabetes, disease severity, and poor response to therapy. Racial differences in rates of obesity and diabetes may contribute to racial differences in hepatic steatosis and treatment response. The aim of the present study was to compare hepatic steatosis and its associations between African American (AA) and Caucasian American (CA) patients with chronic hepatitis C, genotype 1, participating in a prospective study of peginterferon and ribavirin therapy. Liver biopsy results were available from 194 AA patients and 205 CA patients. The 2 groups were compared for anthropometric, clinical, and biochemical features and insulin resistance estimated by the homeostasis model assessment index (HOMA-IR). Sixty-one percent of the AA patients and 65% of the CA patients had hepatic steatosis (P = 0.38). In univariable analysis, steatosis was associated with HOMA-IR, body mass index, waist circumference, serum triglycerides, aminotransferase level, and histological scores for inflammation and fibrosis. After adjusting for these features, AA patients had a lower risk of steatosis than did CA patients (OR 0.54, 95% CI 0.32-0.91, P = 0.02). Insulin resistance but not steatosis was associated with a lower rate of sustained virological response when adjusted for known factors that predict response (relative risk 0.87, 95% CI 0.77-0-99, P = 0.028). Conclusion: After adjusting for the higher prevalence of features associated with hepatic steatosis, AA patients had a lower prevalence of hepatic steatosis than did CA patients with chronic hepatitis C, genotype 1. Insulin resistance but not steatosis was independently associated with lower sustained virological response. C1 Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. NCI, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Conjeevaram, HS (reprint author), Univ Michigan, Div Gastroenterol, 3912 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM omsairam@umich.edu RI Wahed, Abdus/A-6441-2008; OI Wahed, Abdus/0000-0001-6911-7221; Kleiner, David/0000-0003-3442-4453 FU NCRR NIH HHS [M01 RR000042, M01 RR00046, M01 RR00645, M01 RR16500, M02 RR000079]; NIDDK NIH HHS [U01 DK60340, U01 DK60309, U01 DK60324, U01 DK60327, U01 DK60329, U01 DK60335, U01 DK60341, U01 DK60342, U01 DK60344, U01 DK60345, U01 DK60346, U01 DK60349, U01 DK60352] NR 25 TC 124 Z9 129 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2007 VL 45 IS 1 BP 80 EP 87 DI 10.1002/hep.21455 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 122DY UT WOS:000243207100012 PM 17187406 ER PT J AU Yin, H Cheng, LL Langenbach, R Ju, C AF Yin, Hao Cheng, Linling Langenbach, Robert Ju, Cynthia TI Prostaglandin I(2)and E-2 mediate the protective effects of cyclooxygenase-2 in a mouse model of immune-mediated liver injury SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; A-INDUCED HEPATITIS; CONCANAVALIN-A; BERAPROST SODIUM; PROSTACYCLIN ANALOG; CONTROLLED-TRIAL; DEFICIENT MICE; DOUBLE-BLIND; I-2 ANALOG; IFN-GAMMA AB Studies of the molecular and cellular mechanisms of concanavalin A (ConA)-induced liver injury have provided important knowledge on the pathogenesis of many liver diseases involving hepatic inflammation. However, studies identifying hepato-protective factors based on the mechanistic understanding of this model are lacking. Evidence suggests that certain prostaglandin (PG) products of cyclooxygenase (COX)-1 and COX-2 provide important anti-inflammatory and cytoprotective functions in some pathophysiological states. In the present study, we demonstrate a protective role of COX-2 derived PGs in ConA-induced liver injury. COX-2(-/-) mice developed much more severe liver damage upon ConA treatment compared with wild-type and COX-1(-/-) mice. Treatment of COX-2(-/-) mice with misoprostol (a PGE(1/2) analog) or beraprost (a PGI(2) analog) significantly decreased ConA-induced liver injury. Data from both in vivo and in vitro experiments demonstrated that misoprostol and beraprost acted directly on hepatic leukocytes, including natural killer (NK)T and T cells, and down-regulated their production of interferon (IFN)-gamma, which are critical in mediating ConA-induced tissue damage. Collectively, the results provide strong evidence that the protective effects of COX-2 within the liver are mediated through the production of PGE2 and PGI(2), which exert anti-inflammatory functions. These findings suggest that COX-2-derived PGs may have great therapeutic potentials in treating patients with inflammatory liver diseases. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Integrated Dept Immunol, Denver, CO 80262 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Bethesda, MD USA. RP Ju, C (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, 4200 E 9th Ave, Denver, CO 80262 USA. EM cynthia.ju@uchsc.edu FU NIDDK NIH HHS [R21 DK068171]; NIEHS NIH HHS [R01 ES012914] NR 48 TC 32 Z9 34 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2007 VL 45 IS 1 BP 159 EP 169 DI 10.1002/hep.21493 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 122DY UT WOS:000243207100021 PM 17187424 ER PT J AU Luo, WM Yu, QS Holloway, HW Tweedie, D Parrish, D Brossi, A Greig, NH AF Luo, Weiming Yu, Qian-Sheng Holloway, Harold W. Tweedie, David Parrish, Damon Brossi, Arnold Greig, Nigel H. TI Syntheses and anticholinesterase activities of novel 3-aminocarbonylmethylene-3-methyl-2,3-dihydrobenzofuran-5-yl carbamates SO HETEROCYCLES LA English DT Article ID HUMAN ACETYLCHOLINESTERASE; ANALOGS; BUTYRYLCHOLINESTERASE; PHYSOSTIGMINE; INHIBITION; PHENSERINE; METHANOBENZODIOXEPINE; PEPTIDE; ROUTE; ETHER AB Novel carbarnates 4 and 5 were synthesized from starting material 5-hydroxy-3-methyl-3H-benzofuran-2-one, 17. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of 4 and 5 were determined against fresh human enzyme, are in the realm of clinically valuable compounds and are discussed. In addition, the reductive properties of the 2-carbonyl group of 3H-benzofuran-2-one, possessing an unsaturated substituted group in its 3 position (9, 11 and 14), were studied. C1 [Luo, Weiming; Yu, Qian-Sheng; Holloway, Harold W.; Tweedie, David; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Parrish, Damon] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. [Brossi, Arnold] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM GreigN@grc.nia.nih.gov NR 28 TC 0 Z9 0 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PY 2007 VL 71 IS 11 BP 2413 EP 2425 PG 13 WC Chemistry, Organic SC Chemistry GA 268FP UT WOS:000253564800009 ER PT J AU Saunders, RC Aggleton, JP AF Saunders, Richard C. Aggleton, John P. TI Origin and topography of fibers contributing to the fornix in macaque monkeys SO HIPPOCAMPUS LA English DT Article DE entorhinal cortex; hippocampus; memory; primate; subiculum ID VISUAL RECOGNITION MEMORY; HIPPOCAMPAL THETA RHYTHM; MEDIAL TEMPORAL-LOBE; RHESUS-MONKEY; ENTORHINAL CORTEX; BASAL FOREBRAIN; SQUIRREL-MONKEY; PARAHIPPOCAMPAL CORTICES; CHOLINERGIC INNERVATION; HORSERADISH-PEROXIDASE AB The distribution of neurons contributing to the fornix was mapped by placing the retrograde tracer horseradish peroxidase (HRP) in polyacrylamide gels in different medial to lateral locations within the fornix of three rhesus monkeys (Macaca mulatta). The HRP was placed from 3 to 5 mm caudal to the descending columns of the fornix. Additional information came from a series of rhesus and cynomolgus monkeys (Macaca fasciculata) with anterograde tracer injections in the medial temporal lobe. The hippocampal formation, including the subiculum and presubiculum, together with the entorhinal cortex (EC) and perirhinal cortex (area 35) contribute numerous axons to the fornix in a topographical manner. In contrast, the lateral perirhinal cortex (area 36) and parahippocampal cortical areas TF and TH only contained a handful of cells labeled via the fornix. The medial fornix originates from cells in the caudal half of the subiculum, the lamina principalis interna of the caudal half of the presubiculum, and from the perirhinal cortex (area 35). The intermediate portion of the fornix (i.e., that part midway between the midline and most lateral parts of the fornix) originates from cells in the rostral half of the subiculum and prosubiculum, the anterior presubiculum (only from the lamina principalis externa), the caudal presubiculum (primarily from lamina principalis interna), the rostral half of CA3, the EC (primarily 28I and 28M), and the perirhinal cortex (area 35). The lateral parts of the fornix arise from the rostral EC (28L only) and the most rostral portion of CA3. Subcortically, the medial septum, nucleus of the diagonal band, supramammillary nucleus, lateral hypothalamus, dorsal raphe nucleus, and the thalamic nucleus reuniens all send projections through the fornix, which presumably terminate in the hippocampus and adjacent parahippocampal region. These results not only help to define those regions that project via the fornix, but also reveal those subcortical projections to the hippocampal formation most likely to rely entirely on nonfornical pathways. C1 NIMH, Lab Neuropsychol, Bethesda, MD 20892 USA. Univ Cardiff Wales, Sch Psychol, Cardiff, Wales. RP Saunders, RC (reprint author), NIMH, Lab Neuropsychol, 49 Convent Rd, Bethesda, MD 20892 USA. EM richardsaunders@mail.nih.gov OI Aggleton, John/0000-0002-5573-1308 NR 76 TC 57 Z9 58 U1 3 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2007 VL 17 IS 5 BP 396 EP 411 DI 10.1002/hipo.20276 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 164EN UT WOS:000246216400007 PM 17372974 ER PT S AU Prabakaran, P Dimitrov, AS Fouts, TR Dimitrov, DS AF Prabakaran, Ponraj Dimitrov, Antony S. Fouts, Timothy R. Dimitrov, Dimiter S. BE Jeang, KT TI Structure and Function of the HIV Envelope Glycoprotein as Entry Mediator, Vaccine Immunogen, and Target for Inhibitors SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: VIRAL MECHANISMS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; DEPENDENT CELLULAR CYTOTOXICITY; LONG-TERM NONPROGRESSORS; CORECEPTOR-BINDING-SITE; PROXIMAL EXTERNAL REGION; REACTIVE NEUTRALIZING ANTIBODIES; HIV-1/SIV CHIMERIC VIRUS; CHAIN POLYPEPTIDE ANALOG; CHEMOKINE RECEPTOR CCR5 C1 [Prabakaran, Ponraj; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. [Dimitrov, Antony S.; Fouts, Timothy R.] Profectus BioSci Inc, Techctr, UMBC, Baltimore, MD 21227 USA. RP Prabakaran, P (reprint author), NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. OI Fouts, Timothy/0000-0002-2429-2859 FU Intramural NIH HHS NR 275 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-08-054832-6; 978-0-12-373610-9 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2007 VL 55 BP 33 EP 97 DI 10.1016/S1054-3589(07)55002-7 PG 65 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT67 UT WOS:000311374900003 PM 17586312 ER PT S AU Felber, BK Zolotukhin, AS Pavlakis, GN AF Felber, Barbara K. Zolotukhin, Andrei S. Pavlakis, George N. BE Jeang, KT TI Posttranscriptional Control of HIV-1 and Other Retroviruses and Its Practical Applications SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: VIRAL MECHANISMS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; MESSENGER-RNA EXPORT; CONSTITUTIVE TRANSPORT ELEMENT; REV-RESPONSIVE ELEMENT; NUCLEAR-PORE COMPLEX; HTLV-I REX; STRUCTURAL GENE-EXPRESSION; NUCLEOPORIN-LIKE PROTEIN; TRACT-BINDING-PROTEIN; CIS-ACTING SEQUENCES C1 [Felber, Barbara K.; Zolotukhin, Andrei S.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. [Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. RP Felber, BK (reprint author), NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. NR 251 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-08-054832-6 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2007 VL 55 BP 161 EP 197 DI 10.1016/S1054-3589(07)55005-2 PG 37 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT67 UT WOS:000311374900006 PM 17586315 ER PT S AU Strebel, K AF Strebel, Klaus BE Jeang, KT TI HIV Accessory Genes Vif and Vpu SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: VIRAL MECHANISMS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; PIG-TAILED MACAQUES; PROTEIN-U VPU; I-KAPPA-B; VIRION INFECTIVITY FACTOR; UBIQUITIN LIGASE COMPLEX; AMINO-ACID SUBSTITUTIONS; TYPE-2 ENVELOPE PROTEIN; EDITING ENZYME APOBEC3G; VIRAL PARTICLE RELEASE C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NR 193 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-08-054832-6 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2007 VL 55 BP 199 EP 232 DI 10.1016/S1054-3589(07)55006-4 PG 34 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT67 UT WOS:000311374900007 PM 17586316 ER PT S AU Louis, JM Ishima, R Torchia, DA Weber, IT AF Louis, John M. Ishima, Rieko Torchia, Dennis A. Weber, Irene T. BE Jeang, KT TI HIV-1 Protease: Structure, Dynamics, and Inhibition SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: VIRAL MECHANISMS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID VIRUS TYPE-1 PROTEASE; RESOLUTION CRYSTAL-STRUCTURES; DRUG-RESISTANT MUTATIONS; RELAXATION DISPERSION EXPERIMENTS; HUMAN-IMMUNODEFICIENCY; MOLECULAR-DYNAMICS; RETROVIRAL PROTEASES; ACTIVE-SITE; SUBSTRATE RECOGNITION; ENERGY CALCULATIONS C1 [Louis, John M.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Ishima, Rieko] Univ Pittsburgh, Sch Med, Dept Struct Biol, Pittsburgh, PA 15260 USA. [Torchia, Dennis A.] Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD USA. [Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. RP Louis, JM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. FU FIC NIH HHS [TW01001]; Intramural NIH HHS; NIGMS NIH HHS [GM62920, R01 GM062920] NR 110 TC 69 Z9 69 U1 2 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-08-054832-6; 978-0-12-373610-9 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2007 VL 55 BP 261 EP 298 DI 10.1016/S1054-3589(07)55008-8 PG 38 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT67 UT WOS:000311374900009 PM 17586318 ER PT S AU Adamson, CS Freed, EO AF Adamson, Catherine S. Freed, Eric O. BE Jeang, KT TI Human Immunodeficiency Virus Type 1 Assembly, Release, and Maturation SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: VIRAL MECHANISMS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 CAPSID PROTEIN; TYPE-1 MATRIX PROTEIN; RNA PACKAGING SIGNAL; GP41 CYTOPLASMIC TAIL; AMINO-ACID SUBSTITUTIONS; LATE-BUDDING DOMAINS; ROUS-SARCOMA-VIRUS; OPEN READING FRAME; N-TERMINAL DOMAIN C1 [Adamson, Catherine S.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Adamson, CS (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. NR 255 TC 117 Z9 118 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-08-054832-6 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2007 VL 55 BP 347 EP 387 DI 10.1016/S1054-3589(07)55010-6 PG 41 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT67 UT WOS:000311374900011 PM 17586320 ER PT S AU Yeung, ML Bennasser, Y Le, SY Jeang, KT AF Yeung, Man Lung Bennasser, Yamina Le, Shu-Yun Jeang, Kuan-Teh BE Jeang, KT TI RNA Interference and HIV-1 SO HIV-1: MOLECULAR BIOLOGY AND PATHOGENESIS: VIRAL MECHANISMS, 2ND EDITION SE Advances in Pharmacology LA English DT Article; Book Chapter ID IMMUNODEFICIENCY-VIRUS TYPE-1; BINDING PROTEIN; HUMAN-CELLS; ENCODED MICRORNAS; KAPOSIS-SARCOMA; NUCLEAR EXPORT; P-BODIES; INFECTION; INHIBITION; EXPRESSION C1 [Yeung, Man Lung; Bennasser, Yamina; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Le, Shu-Yun] NCI, Ctr Canc Res, Nanobiol Program, NCI Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Yeung, ML (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 58 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-08-054832-6 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2007 VL 55 BP 427 EP 438 DI 10.1016/S1054-3589(07)55013-1 PG 12 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA BCT67 UT WOS:000311374900014 PM 17586323 ER PT J AU Krause, G Jaeschke, H Neumann, S Paschke, R Kleinau, G AF Krause, G. Jaeschke, H. Neumann, S. Paschke, R. Kleinau, G. TI The synergistic conformational effects of all 3 extracellular loops are required for full TSH-Receptor activation SO HORMONE RESEARCH LA English DT Meeting Abstract C1 [Krause, G.; Kleinau, G.] Liebniz Inst Mol Pharmakol Bioinformat & Prot Des, Berlin, Germany. [Jaeschke, H.; Paschke, R.] Univ Leipzig, Dept Med 3, D-7010 Leipzig, Germany. [Neumann, S.] NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2007 VL 68 SU 3 BP 11 EP 11 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240WB UT WOS:000251617800028 ER PT J AU Teolis, I Peffley, EB Wester, DB AF Teolis, Igino Peffley, Ellen B. Wester, David B. TI Comparing student performance in live versus web-based instruction in herbaceous plant identification SO HORTTECHNOLOGY LA English DT Article DE computer; computer-assisted instruction; distance education; learning styles; horticulture education AB A study was conducted to evaluate student performance after receiving the same horticultural lesson through one of two modes of instruction. Students enrolled in an introductory horticulture course received either a traditional herbaceous plant identification (ID) lesson with live plant specimens or the same lesson using only text and photographs on the Internet in one of their laboratory sessions. A follow-up experiment was conducted in which web-based students studied photographs of the exact same plants studied by students receiving traditional instruction. Learning style preferences and demographic information were obtained from surveys. For both experiments, students receiving traditional instruction had higher scores on the plant ID quiz than web-based students. All students were able to identify plants from photographs just as well as from live plant specimens. Visual learners scored higher when receiving traditional instruction when compared with web-based instruction. Student grade point average was positively correlated with quiz score for both experiments. C1 Texas Tech Univ, Dept Plant & Soil Sci, Lubbock, TX 79409 USA. Texas Tech Univ, Dept Range Wildlife & Fisheries Management, Lubbock, TX 79409 USA. RP Teolis, I (reprint author), Natl Ctr Inst & Alternat, 7130 Rutherford Rd, Baltimore, MD 21244 USA. EM iginoteolis@hotmail.com NR 21 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC HORTICULTURAL SCIENCE PI ALEXANDRIA PA 113 S WEST ST, STE 200, ALEXANDRIA, VA 22314-2851 USA SN 1063-0198 J9 HORTTECHNOLOGY JI HortTechnology PD JAN-MAR PY 2007 VL 17 IS 1 BP 120 EP 124 PG 5 WC Horticulture SC Agriculture GA 129WE UT WOS:000243760000021 ER PT S AU Pechhold, K Chakrabarty, S Harlan, DM AF Pechhold, Klaus Chakrabarty, Sagarika Harlan, David M. BE VonHerrath, M Atkinson, M TI Cytotoxic T cell-mediated diabetes in RIP-CD80 transgenic mice - Autoantigen peptide sensitivity and fine specificity SO HOW DO WE BEST EMPLOY ANIMAL MODELS FOR TYPE 1 DIABETES AND MULTIPLE SCLEROSIS? SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on How Do We Best Employ Animal Models for Type 1 Diabetes and Multiple Sclerosis CY NOV 08-09, 2006 CL San Francisco, CA SP Amer Autoimmune Dis Assoc, Autoimmune Dis Res Fdn, Becton Dickinson, Diamyd, Genetech, Juvenile Diabet Res Fdn, Natl Multiple Sclerosis Soc, Thomas Lincoln Casey Fund, Natl Inst Diabet & Digest & Kidney Dis, NIAID, NINDS DE autoantigen-induced diabetes; altered peptide ligands; transgenic mouse; cytotoxic T lymphocytes; immunization; autoimmunity ID PANCREATIC BETA-CELLS; TOLERANCE INDUCTION; INSULIN; ANTIGEN; B7-1; TISSUE; IDENTIFICATION; AUTOIMMUNITY; LYMPHOCYTES; DISEASE AB Rodent immune-mediated diabetes model studies have advanced understanding of beta cell-specific T cell responses, and the testing of therapeutic approaches. We have used an inducible diabetes model based on rat insulin promotor (RIP)-driven expression of CD80 (B7-1) on pancreatic beta cells. Using these mice, we have established that immunizing with a single autoantigen can promote progressive islet inflammation and eventually T cell-mediated diabetes. We now describe a potent immunization protocol using peptide-pulsed mature dendritic cells (DCs) to examine peptide epitopes derived from endogenous (preproinsulin) and transgenically expressed beta cell antigens, namely lymphocytic choriomeningitis virus glycoprotein (LCMV-GP). LCMV-GP epitopes efficiently promote beta cell destruction, and the autoantigenic peptide concentration used to load the DCs correlates directly with diabetes onset. The system allowed us to assess cytotoxic T cell (CTL) fine specificity by immunizing with DCs presenting altered peptide ligands (APLs) of the dominant LCMV-GP epitope, gp33. Finally, using an adoptive transfer system, we tested alternative in vitro T cell activation conditions, including APLs and mitogens, for their impact on T cell effector function and diabetes onset. Our studies revealed a marked discrepancy between (inflammatory) effector functions and diabetes progression, thus emphasizing the importance of structural identity between sensitizing and target epitope and the context of initial T cell activation. C1 NIH, NIDDK, DHHS, Diabet Branch, Bethesda, MD 20892 USA. RP Pechhold, K (reprint author), NIH, NIDDK, Diabet Branch, 10 Ctr Dr,Bldg 10-CRC,Room 5W-5888, Bethesda, MD 20892 USA. EM KlausP@intra.niddk.nih.gov FU Intramural NIH HHS NR 23 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-678-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2007 VL 1103 BP 132 EP 142 DI 10.1196/annals.1394.008 PG 11 WC Medicine, Research & Experimental; Multidisciplinary Sciences SC Research & Experimental Medicine; Science & Technology - Other Topics GA BGG28 UT WOS:000246646400015 PM 17376836 ER PT J AU Peltonen, J Welsh, JA Vahakangas, K AF Peltonen, J. Welsh, J. A. Vahakangas, K. H. TI Is there a role for PCR-SSCP among the methods for missense mutation detection of TP53 gene? SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Review DE comparison of methods; mutation analysis; optimisation; significance of TP53 mutations ID STRAND CONFORMATION POLYMORPHISM; SQUAMOUS-CELL CARCINOMA; POLYMERASE-CHAIN-REACTION; TUMOR-SUPPRESSOR GENE; GRADIENT GEL-ELECTROPHORESIS; P53 FUNCTIONAL ASSAY; LI-FRAUMENI-SYNDROME; LUNG-CANCER; POINT MUTATIONS; BREAST-CANCER AB Mutation analysis methods have increased in variety during the past years. High-throughput microarray methods have especially increased in popularity. However, new methods require reference points, and not all of the methods are equal in sensitivity and specificity. Furthermore, the detection of unknown missense mutations, such as unknown TP53 mutations in human tumors, for clinical purposes requires great accuracy, which may be difficult to acquire with the current high-throughput methods. For these reasons, the classical methods, such as PCR-manual sequencing and PCR-SSCP, are still valuable and necessary. C1 Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland. Univ Oulu, Dept Pharmacol & Toxicol, Oulu, Finland. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Vahakangas, K (reprint author), Univ Kuopio, Dept Pharmacol & Toxicol, POB 1627, FIN-70211 Kuopio, Finland. EM kirsi.vahakangas@uku.fi NR 129 TC 1 Z9 1 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0960-3271 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JAN PY 2007 VL 26 IS 1 BP 9 EP 18 DI 10.1177/0960327107071918 PG 10 WC Toxicology SC Toxicology GA 138BV UT WOS:000244338500002 PM 17334176 ER PT J AU Sadelain, M Boulad, F Galanello, R Giardina, P Locatelli, F Maggio, A Rivella, S Riviere, I Tisdale, J AF Sadelain, Michel Boulad, Farid Galanello, Renzo Giardina, Patricia Locatelli, Franco Maggio, Aurelio Rivella, Stefano Riviere, Isabelle Tisdale, John TI Therapeutic options for patients with severe beta-thalassemia: The need for globin gene therapy SO HUMAN GENE THERAPY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; CORD BLOOD TRANSPLANTATION; ORAL IRON CHELATOR; LENTIVIRAL VECTOR; HEMOGLOBIN DISORDERS; DISEASE; DEFERIPRONE; CHILDREN; SAFETY C1 Mem Sloan Kettering Canc Ctr, Dept Med, Gene Transfer & Gene Express Lab, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Immunol Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Osped Reg Microcitemie, Pediat Clin, I-09121 Cagliari, Italy. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Pediat, New York, NY 10021 USA. Univ Pavia, IRCCS, Policlin San Matteo, I-27100 Pavia, Italy. Azienda Osped Vincenzo Cervello, Div Hematol 2, I-90146 Palermo, Italy. Azienda Osped Vincenzo Cervello, Piera Cutino Res Unit, I-90146 Palermo, Italy. Mem Sloan Kettering Canc Ctr, Gene Transfer & Somat Cell Engn Facil, Dept Med, New York, NY 10021 USA. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Sadelain, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Gene Transfer & Gene Express Lab, New York, NY 10021 USA. EM m-sadelain@ski.mskcc.org RI Rivella, Stefano/A-1597-2010; Maggio, Aurelio/K-7812-2016 OI Rivella, Stefano/0000-0002-0938-6558; Maggio, Aurelio/0000-0002-9601-900X NR 69 TC 27 Z9 27 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2007 VL 18 IS 1 BP 1 EP 9 DI 10.1089/hum.2006.151 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 126QL UT WOS:000243529600001 PM 17173507 ER PT J AU Lind, JM Hutcheson-Dilks, HB Williams, SM Moore, JH Essex, M Ruiz-Pesini, E Wallace, DC Tishkoff, SA O'Brien, SJ Smith, MW AF Lind, Joanne M. Hutcheson-Dilks, Holli B. Williams, Scott M. Moore, Jason H. Essex, Myron Ruiz-Pesini, Eduardo Wallace, Douglas C. Tishkoff, Sarah A. O'Brien, Stephen J. Smith, Michael W. TI Elevated male European and female African contributions to the genomes of African American individuals SO HUMAN GENETICS LA English DT Article DE sex-biased gene flow; admixture ID ADMIXTURE LINKAGE DISEQUILIBRIUM; MULTILOCUS GENOTYPE DATA; HUMAN Y-CHROMOSOME; POPULATION-STRUCTURE; ADMIXED POPULATIONS; GENETIC-STRUCTURE; HUMAN-EVOLUTION; PROPORTIONS; DISEASE; LOCI AB The differential relative contribution of males and females from Africa and Europe to individual African American genomes is relevant to mapping genes utilizing admixture analysis. The assessment of ancestral population contributions to the four types of genomic DNA (autosomes, X and Y chromosomes, and mitochondrial) with their differing modes of inheritance is most easily addressed in males. A thorough evaluation of 93 African American males for 2,018 autosomal single nucleotide polymorphic (SNP) markers, 121 X chromosome SNPs, 10 Y chromosome haplogroups specified by SNPs, and six haplogroup defining mtDNA SNPs is presented. A distinct lack of correlation observed between the X chromosome and the autosomal admixture fractions supports separate treatment of these chromosomes in admixture-based gene mapping applications. The European genetic contributions were highest (and African lowest) for the Y chromosome (28.46%), followed by the autosomes (19.99%), then the X chromosome (12.11%), and the mtDNA (8.51%). The relative order of admixture fractions in the genomic compartments validates previous studies that suggested sex-biased gene flow with elevated European male and African female contributions. There is a threefold higher European male contribution compared with European females (Y chromosome vs. mtDNA) to the genomes of African American individuals meaning that admixture-based gene discovery will have the most power for the autosomes and will be more limited for X chromosome analysis. C1 NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21701 USA. Vanderbilt Univ, Ctr Human Genet Res, Dept Physiol & Mol Biophys, Nashville, TN USA. Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA. Dartmouth Coll Sch Med, Dept Genet, Dept Community & Family Med, Computat Genet Lab,Norris Cotton Canc Ctr, Lebanon, NH USA. Harvard Univ, Sch Publ Hlth, Harvard AIDS Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Cambridge, MA 02138 USA. Univ Calif Irvine, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92717 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. SAIC Frederick Inc, NCI Frederick, Basic Res Program, Frederick, MD USA. Centenary Inst, Agnes Ginges Ctr Mol Cardiol, Sydney, NSW, Australia. RP Smith, MW (reprint author), NCI, SAIC Frederick, Lab Genom Divers, Bldg 560,Rm 21-74, Frederick, MD 21701 USA. EM smithm@ncifcrf.gov RI Smith, Michael/B-5341-2012; Williams, Scott/B-9491-2012 FU NCI NIH HHS [N01-CO-12400] NR 49 TC 44 Z9 45 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2007 VL 120 IS 5 BP 713 EP 722 DI 10.1007/s00439-006-0261-7 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 119GM UT WOS:000243000800012 PM 17006671 ER PT J AU Khan, SY Riazuddin, S Tariq, M Anwar, S Shabbir, MI Riazuddin, SA Khan, SN Husnain, T Ahmed, ZM Friedman, TB Riazuddin, S AF Khan, Shahid Y. Riazuddin, Saima Tariq, Muhammad Anwar, Saima Shabbir, Muhammad I. Riazuddin, S. Amer Khan, Shaheen N. Husnain, Tayyab Ahmed, Zubair M. Friedman, Thomas B. Riazuddin, Sheikh TI Autosomal recessive nonsyndromic deafness locus DFNB63 at chromosome 11q13.2-q13.3 SO HUMAN GENETICS LA English DT Article DE deafness; DFNB63; Pakistan; 11q13.2-q13.3 ID DOMINANT DEAFNESS; HEARING-LOSS; INNER-EAR; GENE; MUTATIONS; DEFECTS; KCNQ4; INT-2; CELLS; MAPS AB A genome wide linkage analysis of nonsyndromic deafness segregating in a consanguineous Pakistani family (PKDF537) was used to identify DFNB63, a new locus for congenital profound sensorineural hearing loss. A maximum two-point lod score of 6.98 at theta = 0 was obtained for marker D11S1337 (68.55 cM). Genotyping of 550 families revealed three additional families (PKDF295, PKDF702 and PKDF817) segregating hearing loss linked to chromosome 11q13.2-q13.3. Meiotic recombination events in these four families define a critical interval of 4.81 cM bounded by markers D11S4113 (68.01 cM) and D11S4162 (72.82 cM), and SHANK2, FGF-3, TPCN2 and CTTN are among the candidate genes in this interval. Positional identification of this deafness gene should reveal a protein necessary for normal development and/or function of the auditory system. C1 Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd,Thokar Niaz Baig, Lahore 53700, Pakistan. EM riaz@lhr.comsats.net.pk RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015; Anwar, Saima/C-7477-2016; SHEIKH, RIAZUDDIN/L-2406-2015 FU Intramural NIH HHS NR 21 TC 18 Z9 18 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2007 VL 120 IS 6 BP 789 EP 793 DI 10.1007/s00439-006-0275-1 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 127SH UT WOS:000243606100006 PM 17066295 ER PT J AU Nicodemus, KK Kolachana, BS Vakkalanka, R Straub, RE Giegling, I Egan, MF Rujescu, D Weinberger, DR AF Nicodemus, Kristin K. Kolachana, Bhaskar S. Vakkalanka, Radhakrishna Straub, Richard E. Giegling, Ina Egan, Michael F. Rujescu, Dan Weinberger, Daniel R. TI Evidence for statistical epistasis between catechol-O-methyltransferase (COMT) and polymorphisms in RGS4, G72 (DAOA), GRM3, and DISC1: influence on risk of schizophrenia SO HUMAN GENETICS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; BIPOLAR-AFFECTIVE-DISORDER; AMINO-ACID OXIDASE; CHINESE POPULATION; PREFRONTAL CORTEX; HAPLOTYPE RECONSTRUCTION; GENETIC ASSOCIATION; SUSCEPTIBILITY GENE; POWER CALCULATIONS; WORKING-MEMORY AB Catechol-O-methyltransferase (COMT) regulates dopamine degradation and is located in a genomic region that is deleted in a syndrome associated with psychosis, making it a promising candidate gene for schizophrenia. COMT also has been shown to influence prefrontal cortex processing efficiency. Prefrontal processing dysfunction is a common finding in schizophrenia, and a background of inefficient processing may modulate the effect of other candidate genes. Using the NIMH sibling study (SS), a non-independent case-control set, and an independent German (G) case-control set, we performed conditional/unconditional logistic regression to test for epistasis between SNPs in COMT (rs2097603, Val158Met (rs4680), rs165599) and polymorphisms in other schizophrenia susceptibility genes. Evidence for interaction was evaluated using a likelihood ratio test (LRT) between nested models. SNPs in RGS4, G72, GRM3, and DISC1 showed evidence for significant statistical epistasis with COMT. A striking result was found in RGS4: three of five SNPs showed a significant increase in risk [LRT P-values: 90387 = 0.05 (SS); SNP4 = 0.02 (SS), 0.02 (G); SNP18 = 0.04 (SS), 0.008 (G)] in interaction with COMT; main effects for RGS4 SNPs were null. Significant results for SNP4 and SNP18 were also found in the German study. We were able to detect statistical interaction between COMT and polymorphisms in candidate genes for schizophrenia, many of which had no significant main effect. In addition, we were able to replicate other studies, including allelic directionality. The use of epistatic models may improve replication of psychiatric candidate gene studies. C1 NIMH, Genes Cognit & Psychosis Program, IRP, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, IRP, NIH, Rm 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov NR 81 TC 92 Z9 96 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2007 VL 120 IS 6 BP 889 EP 906 DI 10.1007/s00439-006-0257-3 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 127SH UT WOS:000243606100016 PM 17006672 ER PT J AU Goddard, KAB Tromp, G Romero, R Olson, JM Lu, Q Xu, ZY Parimi, N Nien, JK Gomez, R Behnke, E Solari, M Espinoza, J Santolaya, J Chaiworapongsa, T Lenk, GM Volkenant, K Anant, MK Salisbury, BA Carr, J Lee, MS Vovis, GF Kuivaniemi, H AF Goddard, Katrina A. B. Tromp, Gerard Romero, Roberto Olson, Jane M. Lu, Qing Xu, Zhiying Parimi, Neeta Nien, Jyh Kae Gomez, Ricardo Behnke, Ernesto Solari, Margarita Espinoza, Jimmy Santolaya, Joaquin Chaiworapongsa, Tinnakorn Lenk, Guy M. Volkenant, Kimberly Anant, Madan Kumar Salisbury, Benjamin A. Carr, Janet Lee, Min Soeb Vovis, Gerald F. Kuivaniemi, Helena TI Candidate-gene association study of mothers with pre-eclampsia, and their infants, analyzing 775 SNPs in 190 genes SO HUMAN HEREDITY LA English DT Review DE genetic association study; maternal-fetal interaction; interleukin 1; type I collagen; haplotype analysis; hispanic population ID FACTOR-V-LEIDEN; TUMOR-NECROSIS-FACTOR; PLASMINOGEN-ACTIVATOR INHIBITOR-1; GENOME-WIDE SCAN; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; SINGLE NUCLEOTIDE POLYMORPHISMS; MATERNAL SUSCEPTIBILITY LOCUS; ANGIOTENSIN-CONVERTING ENZYME; MICROSOMAL EPOXIDE HYDROLASE; HARDY-WEINBERG EQUILIBRIUM AB Pre-eclampsia (PE) affects 5-7% of pregnancies in the US, and is a leading cause of maternal death and perinatal morbidity and mortality worldwide. To identify genes with a role in PE, we conducted a large-scale association study evaluating 775 SNPs in 190 candidate genes selected for a potential role in obstetrical complications. SNP discovery was performed by DNA sequencing, and genotyping was carried out in a high-throughput facility using the MassARRAY (TM) System. Women with PE (n = 394) and their offspring (n = 324) were compared with control women (n = 602) and their offspring (n = 631) from the same hospital-based population. Haplotypes were estimated for each gene using the EM algorithm, and empirical p values were obtained for a logistic regression-based score test, adjusted for significant covariates. An interaction model between maternal and offspring geno-types was also evaluated. The most significant findings for association with PE were COL1A1 (p = 0.0011) and IL1A (p = 0.0014) for the maternal genotype, and PLAUR (p = 0.0008) for the offspring genotype. Common candidate genes for PE, including MTHFR and NOS3, were not significantly associated with PE. For the interaction model, SNPs within IGF1 (p = 0.0035) and IL4R (p = 0.0036) gave the most significant results. This study is one of the most comprehensive genetic association studies of PE to date, including an evaluation of offspring genotypes that have rarely been considered in previous studies. Although we did not identify statistically significant evidence of association for any of the candidate loci evaluated here after adjusting for multiple testing using the false discovery rate, additional compelling evidence exists, including multiple SNPs with nominally significant p values in COL1A1 and the IL1A region, and previous reports of association for IL1A, to support continued interest in these genes as candidates for PE. Identification of the genetic regulators of PE may have broader implications, since women with PE are at increased risk of death from cardiovascular diseases later in life. Copyright (c) 2007 S. Karger AG, Basel. C1 Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Wayne State Univ, Dept Surg, Detroit, MI 48201 USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. NICHD, Perinatol Res Branch, NIH, Bethesda, MD USA. Pontificia Univ Catolica Chile, Sotero Rio Hosp, Ctr Perinatal Diag & Res, Santiago, Chile. Genaissance Pharmaceut, New Haven, CT USA. RP Kuivaniemi, H (reprint author), Wayne State Univ, Sch Med, Ctr Mol Med & Genet, 3317 Gordon H Scott Hall Basic Med Sci,540 E Cran, Detroit, MI 48201 USA. EM kuivan@sanger.med.wayne.edu RI Lenk, Guy/Q-1226-2016; Tromp, Gerard/B-2677-2017; OI Lenk, Guy/0000-0001-8092-1405; Tromp, Gerard/0000-0002-7761-0806; Salisbury, Benjamin/0000-0003-0796-6492; Kuivaniemi, Helena/0000-0001-5753-8766 FU Intramural NIH HHS; NCRR NIH HHS [RR03655] NR 130 TC 54 Z9 58 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2007 VL 63 IS 1 BP 1 EP 16 DI 10.1159/000097926 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 127DF UT WOS:000243564800001 PM 17179726 ER PT J AU Shtir, C Nagakawa, IS Duren, WL Conneely, KN Scott, LJ Silander, K Valle, TT Tuomilehto, J Buchanan, TA Bergman, RN Collins, FS Boehnke, M Watanabe, RM AF Shtir, Corina Nagakawa, I. Sharon Duren, William L. Conneely, Karen N. Scott, Laura J. Silander, Kaisa Valle, Timo T. Tuomilehto, Jaakko Buchanan, Thomas A. Bergman, Richard N. Collins, Francis S. Boehnke, Michael Watanabe, Richard M. TI Subsets of finns with high HDL to total cholesterol ratio show evidence for linkage to type 2 diabetes on chromosome 6q SO HUMAN HEREDITY LA English DT Article DE linkage analysis; heterogeneity; type 2 diabetes; HDL cholesterol; ordered subsets analysis; chromosome 6q ID GENOME-WIDE SEARCH; MELLITUS GENETICS FUSION; GLYCOPROTEIN PC-1 GENE; SUSCEPTIBILITY GENES; INSULIN-RESISTANCE; MEXICAN-AMERICANS; K121Q POLYMORPHISM; CANDIDATE LOCI; MAPPING GENES; SCAN AB Objectives: The purpose of this study was to examine carefully heterogeneity underlying evidence for linkage to type 2 diabetes (T2DM) on chromosome 6q from two sets of FUSION families. Methods: Ordered subsets analysis (OSA) was performed on two sets of FUSION families. For OSA results showing significant improvement in evidence for linkage, T2DM-related phenotypes were compared between individuals with T2DM within the subset versus the complement. Results: OSA analysis revealed 105 families with the highest average HDL to total cholesterol ratio (HDL ratio) that had strongly increased evidence for linkage (MLS = 7.91 at 78.0 cM; uncorrected p = 0.00002). Subjects with T2DM within this subset were significantly leaner, had lower fasting glucose, insulin, and C-peptide, and more favorable cardiovascular risk profile compared to the complement set of subjects with T2DM. OSA also revealed 33 families with the lowest average fasting insulin that had increased evidence for linkage at a second locus (MLS = 3.45 at 128 cM; uncorrected p = 0.017) coincident with quantitative trait locus linkage analysis results for fasting and 2-hour insulin in subjects without T2DM. Conclusions: These results suggest two diabetes susceptibility loci on chromosome 6q that may affect subsets of individuals with a milder form of T2DM. Copyright (c) 2007 S. Karger AG, Basel. C1 Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA 90089 USA. Univ So Calif, Div Endocrinol & Diabet, Dept Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90089 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. NIH, Genome Technol Branch, Natl Human Genome Res Ctr, Bethesda, MD 20892 USA. Univ Helsinki, Diabet & Genet Epidemiol Unit, Dept Epidemiol & Hlth Promot, Natl Publ Hlth Inst, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. S Ostrobothnia Cent Hosp, Seinajoki, Finland. RP Watanabe, RM (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, 1540 Alcazar St,CHP-220, Los Angeles, CA 90089 USA. EM rwatanab@usc.edu FU Intramural NIH HHS; NHGRI NIH HHS [HG00376, R01 HG000376-22, N01 HG065403, N01HG65403, R01 HG000376]; NIDDK NIH HHS [R56 DK062370, R01 DK029867, R37 DK027619, DK27619, U01 DK062370, R01 DK027619-22, DK29867, R01 DK062370-05, R01 DK062370, R01 DK029867-24, R01 DK027619, DK62370] NR 41 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2007 VL 63 IS 1 BP 17 EP 25 DI 10.1159/000097927 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 127DF UT WOS:000243564800002 PM 17179727 ER PT J AU Manolio, TA Collins, FS AF Manolio, Teri A. Collins, Francis S. TI Genes, environment, health, and disease: Facing up to complexity SO HUMAN HEREDITY LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; CORONARY HEART-DISEASE; FOLLOW-UP; RISK-FACTOR; FRAMINGHAM; POLYMORPHISM; POPULATION; EXPERIENCE; EXPOSURE; COHORT C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, 31 Ctr Dr,Bldg 31,Room 4B09, Bethesda, MD 20892 USA. EM FSCollins@mail.nih.gov NR 42 TC 28 Z9 28 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PY 2007 VL 63 IS 2 BP 63 EP 66 DI 10.1159/000099178 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 136XD UT WOS:000244256500001 PM 17283435 ER PT J AU Zheng, G Song, K Elston, RC AF Zheng, Gang Song, Kijoung Elston, Robert C. TI Adaptive two-stage analysis of genetic association in case-control designs SO HUMAN HEREDITY LA English DT Article DE conditional power; genomewide association; Hardy-Weinberg disequilibrium; self-replication; trend test ID HARDY-WEINBERG EQUILIBRIUM; MACULAR DEGENERATION; SAMPLE-SIZE; DISEASE ASSOCIATION; TREND TESTS; POWER; DISEQUILIBRIUM; SUSCEPTIBILITY; MARKERS; LOCUS AB We study a two-stage analysis of genetic association for case-control studies. In the first stage, we compare Hardy-Weinberg disequilibrium coefficients between cases and controls and, in the second stage, we apply the Cochran-Armitage trend test. The two analyses are statistically independent when Hardy-Weinberg equilibrium holds in the population, so all the samples are used in both stages. The significance level in the first stage is adaptively determined based on its conditional power. Given the level in the first stage, the level for the second stage analysis is determined with the overall Type I error being asymptotically controlled. For finite sample sizes, a parametric bootstrap method is used to control the overall Type I error rate. This two-stage analysis is often more powerful than the Cochran-Armitage trend test alone for a large association study. The new approach is applied to SNPs from a real study. Copyright (c) 2007 S. Karger AG, Basel. C1 NHLBI, Off Biostat Res, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov FU NCRR NIH HHS [RR03655]; NIGMS NIH HHS [GM28356]; PHS HHS [P30CAD43703] NR 31 TC 17 Z9 18 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2007 VL 63 IS 3-4 BP 175 EP 186 DI 10.1159/000099830 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 146RP UT WOS:000244952500004 PM 17310127 ER PT J AU Zang, Y Zhang, H Yang, YN Zheng, G AF Zang, Yong Zhang, Hong Yang, Yaning Zheng, Gang TI Robust genomic control and robust delta centralization tests for case-control association studies SO HUMAN HEREDITY LA English DT Article DE Cochran-Armitage trend tests; cryptic relatedness; genetic models; population stratification; robust tests ID POPULATION STRATIFICATION; GENETIC ASSOCIATION; TREND TESTS; SAMPLE-SIZE; MARKERS; POWER; SURVIVAL AB The population-based case-control design is a powerful approach for detecting susceptibility markers of a complex disease. However, this approach may lead to spurious association when there is population substructure: population stratification (PS) or cryptic relatedness (CR). Two simple approaches to correct for the population substructure are genomic control (GC) and delta centralization (DC). GC uses the variance inflation factor to correct for the variance distortion of a test statistic, and the DC centralizes the non-central chi-square distribution of the test statistic. Both GC and DC have been studied for case-control association studies mainly under a specific genetic model (e.g. recessive, additive or dominant), under which an optimal trend test is available. The genetic model is usually unknown for many complex diseases. In this situation, we study the performance of three robust tests based on the GC and DC corrections in the presence of the population substructure. Our results show that, when the genetic model is unknown, the DC- (or GC-) corrected maximum and Pearson's association test are robust and have good control of Type I error and high power relative to the optimal trend tests in the presence of PS (or CR). Copyright (c) 2007 S. Karger AG, Basel. C1 NHLBI, Off Biostat Res, Bethesda, MD 20891 USA. Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20891 USA. EM zhengg@nhlbi.nih.gov NR 28 TC 7 Z9 7 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2007 VL 63 IS 3-4 BP 187 EP 195 DI 10.1159/000099831 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 146RP UT WOS:000244952500005 PM 17310128 ER PT J AU Chen, JB Chatterjee, N AF Chen, Jinbo Chatterjee, Nilanjan TI Exploiting Hardy-Weinberg equilibrium for efficient screening of single SNP associations from case-control studies SO HUMAN HEREDITY LA English DT Article DE association test; case-control study; genome scan; Hardy-Weinberg equilibrium; retrospective likelihood ID SAMPLE-SIZE; INFERENCE; GENES; TESTS; POWER AB In case-control studies, the assessment of the association between a binary disease outcome and a single nucleotide polymorphism (SNP) is often based on comparing the observed genotype distribution for the cases against that for the controls. In this article, we investigate an alternative analytic strategy in which the observed genotype frequencies of cases are compared against the expected genotype frequencies of controls assuming Hardy-Weinberg Equilibrium (HWE). Assuming HWE for controls, we derive closed-form expressions for maximum likelihood estimates of the genotype-specific disease odds ratio (OR) parameters and related variance-covariances. Based on these estimates and their variance-covariance structure, we then propose a two-degree-of- freedom test for disease-SNP association. We show that the proposed test can have substantially higher power than a variety of existing methods, especially when the true effect of the SNP is recessive. We also obtain analytic expressions for the bias of the OR estimates when the underlying HWE assumption is violated. We conclude that the novel test would be particularly useful for analyzing data from the initial 'screening' stages of contemporary multi-stage association studies. Copyright (c) 2007 S. Karger AG, Basel. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Chen, JB (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 423 Guardian Dr, Philadelphia, PA 19104 USA. EM jchen@cceb.med.upenn.edu NR 16 TC 28 Z9 28 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2007 VL 63 IS 3-4 BP 196 EP 204 DI 10.1159/000099996 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 146RP UT WOS:000244952500006 PM 17317968 ER PT J AU Kristie, TM AF Kristie, Thomas M. BE Arvin, A CampadelliFiume, G Mocarski, E Moore, PS Roizman, B Whitley, R Yamanishi, K TI Early events pre-initiation of alphaherpes viral gene expression SO HUMAN HERPESVIRUSES: BIOLOGY, THERAPY, AND IMMUNOPROPHYLAXIS LA English DT Article; Book Chapter ID HERPES-SIMPLEX-VIRUS; HOST-CELL FACTOR; GA-BINDING-PROTEIN; OCT-1 POU DOMAIN; TRANSCRIPTIONAL COACTIVATOR HCF-1; IMMEDIATE-EARLY PROTEIN; ACTIVATION DOMAIN; TRANSACTIVATOR VP16; CRYSTAL-STRUCTURE; C1 HCF C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Kristie, TM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 116 TC 9 Z9 9 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-82714-0 PY 2007 BP 112 EP 127 D2 10.2277/ 0521827140 PG 16 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BXR52 UT WOS:000296850300009 ER PT J AU Cohen, JI AF Cohen, Jeffrey I. BE Arvin, A CampadelliFiume, G Mocarski, E Moore, PS Roizman, B Whitley, R Yamanishi, K TI VZV: molecular basis of persistence (latency and reactivation) SO HUMAN HERPESVIRUSES: BIOLOGY, THERAPY, AND IMMUNOPROPHYLAXIS LA English DT Article; Book Chapter ID VARICELLA-ZOSTER-VIRUS; HUMAN TRIGEMINAL GANGLIA; DORSAL-ROOT GANGLIA; HERPES-SIMPLEX-VIRUS; POLYMERASE-CHAIN-REACTION; AFRICAN-GREEN MONKEYS; IMMEDIATE-EARLY PROTEIN; HUMAN SENSORY NEURONS; REPLICATION IN-VITRO; SIMIAN VARICELLA C1 [Cohen, Jeffrey I.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Cohen, Jeffrey I.] NIH, Clin Invest Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Lab Clin Infect Dis, Bldg 10, Bethesda, MD 20892 USA. NR 77 TC 4 Z9 4 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-82714-0 PY 2007 BP 689 EP 699 D2 10.2277/ 0521827140 PG 11 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BXR52 UT WOS:000296850300039 ER PT J AU Eniafe, RB Rezvani, K Barrett, AJ AF Eniafe, Rhoda B. Rezvani, Katayoun Barrett, A. John TI CD8+T-cell responses to peptides derived from PRAME occur in patients with acute myelogenous leukemia and in healthy donors SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 08-12, 2007 CL Minneapolis, MN SP Amer Soc Histocompatibil & Immunogenet C1 [Eniafe, Rhoda B.; Rezvani, Katayoun; Barrett, A. John] NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2007 VL 68 SU 1 BP S68 EP S68 DI 10.1016/j.humimm.2007.08.130 PG 1 WC Immunology SC Immunology GA 217EF UT WOS:000249930500120 ER PT J AU Fadeyi, E Stroncek, D Peterson, B Hackett, J Adams, S AF Fadeyi, Emmanuel Stroncek, David Peterson, Brett Hackett, Julia Adams, Sharon TI Analysis of a high throughput method for screening HLA antibodies in platelet donors SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 08-12, 2007 CL Minneapolis, MN SP Amer Soc Histocompatibil & Immunogenet C1 [Fadeyi, Emmanuel; Stroncek, David; Peterson, Brett; Hackett, Julia; Adams, Sharon] NIH, DTM, HLA, 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2007 VL 68 SU 1 BP S105 EP S105 DI 10.1016/j.humimm.2007.08.202 PG 1 WC Immunology SC Immunology GA 217EF UT WOS:000249930500191 ER PT J AU Pellett, FJ Chandran, V Martin, MP Carrington, M Gladman, DD AF Pellett, Fawnda J. Chandran, Vinod Martin, Maureen P. Carrington, Mary Gladman, Dafna D. TI Unusual KIR haplotypes in patients with psoriatic arthritis and their family members SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 08-12, 2007 CL Minneapolis, MN SP Amer Soc Histocompatibil & Immunogenet C1 [Pellett, Fawnda J.; Chandran, Vinod; Gladman, Dafna D.] Univ Toronto, Toronto Western Res Inst, Toronto, ON, Canada. [Martin, Maureen P.; Carrington, Mary] Sci Applicat Int Corp Frederick, Natl Canc Inst, Lab Genom Diversity, Frederick, 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2007 VL 68 SU 1 BP S57 EP S57 DI 10.1016/j.humimm.2007.08.107 PG 1 WC Immunology SC Immunology GA 217EF UT WOS:000249930500097 ER PT J AU Savani, BN Mielke, S Adams, S Uribe, M Rezvani, K Young, A Kurlander, R Srinivasan, R Childs, R Hensel, N Barrett, J AF Savani, Bipin N. Mielke, Stephen Adams, Sharon Uribe, Marcela Rezvani, Katayoun Young, Agnes Kurlander, Roger Srinivasan, Ramaprasad Childs, Richard Hensel, Nancy Barrett, John TI Interaction of HLA KIR matching/mismatching with natural killer cell recovery in T cell depleted HLA identical stem cell transplantation SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 08-12, 2007 CL Minneapolis, MN SP Amer Soc Histocompatibil & Immunogenet C1 [Savani, Bipin N.; Mielke, Stephen; Young, Agnes; Childs, Richard; Hensel, Nancy; Barrett, John] NIH, Stem Cell Transplantat Sect, Hematol Branch, Bethesda, MD 20892 USA. [Adams, Sharon; Uribe, Marcela; Kurlander, Roger] NIH, DTM, CC, Bethesda, MD USA. [Srinivasan, Ramaprasad] NIH, NCI, Urol Oncol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2007 VL 68 SU 1 BP S68 EP S68 DI 10.1016/j.humimm.2007.08.129 PG 1 WC Immunology SC Immunology GA 217EF UT WOS:000249930500119 ER PT J AU Single, RM Martin, MP Gao, XJ Meyer, D Yeager, M Kidd, JR Kidd, KK Carrington, M AF Single, Richard M. Martin, Maureen P. Gao, Xiaojiang Meyer, Diogo Yeager, Meredith Kidd, Judith R. Kidd, Kenneth K. Carrington, Mary TI Global diversity of KIR and HLA: Population-level evidence for coevolution, natural selection, and signatures of demographic history SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 08-12, 2007 CL Minneapolis, MN SP Amer Soc Histocompatibil & Immunogenet C1 [Single, Richard M.] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA. [Martin, Maureen P.; Gao, Xiaojiang; Carrington, Mary] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Meyer, Diogo] Univ Sao Paulo, Dept Genet & Evolut Biol, BR-05508 Sao Paulo, Brazil. [Yeager, Meredith] NIH, NCI, Core Genotype Facil, Bethesda, MD 20892 USA. [Kidd, Judith R.; Kidd, Kenneth K.] Yale Univ, Dept Genet, New Haven, CT 06520 USA. RI Meyer, Diogo/A-1868-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2007 VL 68 SU 1 BP S10 EP S10 DI 10.1016/j.humimm.2007.08.009 PG 1 WC Immunology SC Immunology GA 217EF UT WOS:000249930500005 ER PT J AU Uribe, M Adams, S Chouchane, L Stronscek, D Marincola, F AF Uribe, Marcela Adams, Sharon Chouchane, Lotfi Stronscek, David Marincola, Francesco TI KIR genotypes in Tunisian population SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 08-12, 2007 CL Minneapolis, MN SP Amer Soc Histocompatibil & Immunogenet C1 [Uribe, Marcela; Adams, Sharon; Stronscek, David; Marincola, Francesco] NIH, HLA, DTM, 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2007 VL 68 SU 1 BP S64 EP S64 DI 10.1016/j.humimm.2007.08.122 PG 1 WC Immunology SC Immunology GA 217EF UT WOS:000249930500112 ER PT J AU Simon-Sanchez, J Scholz, S Fung, HC Matarin, M Hernandez, D Gibbs, JR Britton, A de Vrieze, FW Peckham, E Gwinn-Hardy, K Crawley, A Keen, JC Nash, J Borgaonkar, D Hardy, J Singleton, A AF Simon-Sanchez, Javier Scholz, Sonja Fung, Hon-Chung Matarin, Mar Hernandez, Dena Gibbs, J. Raphael Britton, Angela de Vrieze, Fabienne Wavrant Peckham, Elizabeth Gwinn-Hardy, Katrina Crawley, Anthony Keen, Judith C. Nash, Josefina Borgaonkar, Digamber Hardy, John Singleton, Andrew TI Genome-wide SNP assay reveals structural genomic variation, extended homozygosity and cell-line induced alterations in normal individuals SO HUMAN MOLECULAR GENETICS LA English DT Article ID EPSTEIN-BARR VIRUS; CHROMOSOMAL-ABERRATIONS; POLYMORPHISM; REGION; 13Q14 AB The recent hapmap effort has placed focus on the application of genome- wide SNP analysis to assess the contribution of genetic variability, particularly SNPs, to traits such as disease. Here, we describe the utility of genome-wide SNP analysis in the direct detection of extended homozygosity and structural genomic variation. We use this approach to assess the frequency of genomic alterations resulting from the lymphoblast immortalization and culture processes commonly used in cell repositories. We have assayed 408 804 SNPs in 276 DNA samples extracted from Epstein-Barr virus immortalized cell lines, which were derived from lymphocytes of elderly neurologically normal subjects. These data reveal extended homozygosity (contiguous tracts > 5 Mb) in 9.5% (26/272) and 340 structural genomic alterations in 182 (66.9%) DNA samples assessed, 66% of which did not overlap with previously described structural variations. Examination of DNA extracted directly from the blood of 30 of these subjects confirmed all examined instances of extended homozygosity (6/6), 75% of structural genomic alteration < 5 Mb in size (12/16) and 13% (1/8) of structural genomic alteration > 5 Mb in size. These data suggest that structural genomic variation is a common phenomenon in the general population. While a proportion of this variability may be caused or its relative abundance altered by the immortalization and clonal process this will have only a minor effect on genotype and allele frequencies in a large cohort. It is likely that this powerful methodology will augment existing techniques in the identification of chromosomal abnormalities. C1 CSIC, Inst Biomed Valencia, Mol Genet Unit, Valencia 46010, Spain. CSIC, Inst Biomed Valencia, Unidad Genet Mol, Dept Genom & Proteom, Valencia 46010, Spain. UCL, Neurogenet Lab, London, England. UCL, Retalila Western Inst Neurol Studies, London, England. Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan. Chang Gung Univ, Coll Med, Taipei, Taiwan. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NIA, Computat Biol Core, NIH, Bethesda, MD 20892 USA. Coriell Inst Med Res, Camden, NJ USA. RP Singleton, A (reprint author), CSIC, Inst Biomed Valencia, Mol Genet Unit, Valencia 46010, Spain. EM singleta@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009; Gibbs, J. Raphael/A-3984-2010; Hardy, John/C-2451-2009; Matarin, Mar/F-1771-2016; OI Matarin, Mar/0000-0002-4717-5735; Gwinn, Katrina/0000-0002-8277-651X; Scholz, Sonja/0000-0002-6623-0429 FU Intramural NIH HHS; Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 19 TC 156 Z9 158 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2007 VL 16 IS 1 BP 1 EP 14 DI 10.1093/hmg/ddl436 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 127MY UT WOS:000243591600001 PM 17116639 ER PT J AU Bierut, LJ Madden, PAF Breslau, N Johnson, EO Hatsukami, D Pomerleau, OF Swan, GE Rutter, J Bertelsen, S Fox, L Fugman, D Goate, AM Hinrichs, AL Konvicka, K Martin, NG Montgomery, GW Saccone, NL Saccone, SF Wang, JC Chase, GA Rice, JP Ballinger, DG AF Bierut, Laura Jean Madden, Pamela A. F. Breslau, Naomi Johnson, Eric O. Hatsukami, Dorothy Pomerleau, Ovide F. Swan, Gary E. Rutter, Joni Bertelsen, Sarah Fox, Louis Fugman, Douglas Goate, Alison M. Hinrichs, Anthony L. Konvicka, Karel Martin, Nicholas G. Montgomery, Grant W. Saccone, Nancy L. Saccone, Scott F. Wang, Jen C. Chase, Gary A. Rice, John P. Ballinger, Dennis G. TI Novel genes identified in a high-density genome wide association study for nicotine dependence SO HUMAN MOLECULAR GENETICS LA English DT Article ID ALPHA-T-CATENIN; PSYCHIATRIC-DISORDERS; SUBSTANCE DEPENDENCE; SMOKING PERSISTENCE; ALZHEIMERS-DISEASE; HABITUAL SMOKING; SUBUNIT GENE; COMMON; LOCI; VULNERABILITY AB Tobacco use is a leading contributor to disability and death worldwide, and genetic factors contribute in part to the development of nicotine dependence. To identify novel genes for which natural variation contributes to the development of nicotine dependence, we performed a comprehensive genome wide association study using nicotine dependent smokers as cases and non-dependent smokers as controls. To allow the efficient, rapid, and cost effective screen of the genome, the study was carried out using a two-stage design. In the first stage, genotyping of over 2.4 million single nucleotide polymorphisms (SNPs) was completed in case and control pools. In the second stage, we selected SNPs for individual genotyping based on the most significant allele frequency differences between cases and controls from the pooled results. Individual genotyping was performed in 1050 cases and 879 controls using 31 960 selected SNPs. The primary analysis, a logistic regression model with covariates of age, gender, genotype and gender by genotype interaction, identified 35 SNPs with P-values less than 10(-4) (minimum P-value 1.53 x 10(-6)). Although none of the individual findings is statistically significant after correcting for multiple tests, additional statistical analyses support the existence of true findings in this group. Our study nominates several novel genes, such as Neurexin 1 (NRXN1), in the development of nicotine dependence while also identifying a known candidate gene, the beta 3 nicotinic cholinergic receptor. This work anticipates the future directions of large-scale genome wide association studies with state-of-the-art methodological approaches and sharing of data with the scientific community. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Michigan State Univ, E Lansing, MI 48824 USA. Res Triangle Inst Int, Res Triangle Pk, NC USA. Univ Minnesota, Minneapolis, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. SRI Int, Menlo Pk, CA 94025 USA. NIDA, Rockville, MD USA. Rutgers State Univ, Piscataway, NJ USA. Perlegen Sci, Mountain View, CA USA. Queensland Inst Med Res, Herston, Qld 4006, Australia. Penn State Coll Med, Hershey, PA USA. RP Bierut, LJ (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid,Box 8134, St Louis, MO 63110 USA. EM bierutl@msnotes.wustl.edu RI Breslau , Naomi/I-3196-2012; Montgomery, Grant/B-7148-2008; OI Montgomery, Grant/0000-0002-4140-8139; Rutter, Joni/0000-0002-6502-2361; Martin, Nicholas/0000-0003-4069-8020 FU NCI NIH HHS [CA89392, P01 CA089392, P01 CA089392-05]; NIDA NIH HHS [DA12854, DA015129, K01 DA015129, N01DA-0-7079, R01 DA012854, R56 DA012854] NR 40 TC 373 Z9 378 U1 4 U2 25 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 JAN 1 PY 2007 VL 16 IS 1 BP 24 EP 35 DI 10.1093/hmg/ddl441 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 127MY UT WOS:000243591600003 PM 17158188 ER PT J AU Saccone, SF Hinrichs, AL Saccone, NL Chase, GA Konvicka, K Madden, PAF Breslau, N Johnson, EO Hatsukami, D Pomerleau, O Swan, GE Goate, AM Rutter, J Bertelsen, S Fox, L Fugman, D Martin, NG Montgomery, GW Wang, JC Ballinger, DG Rice, JP Bierut, LJ AF Saccone, Scott F. Hinrichs, Anthony L. Saccone, Nancy L. Chase, Gary A. Konvicka, Karel Madden, Pamela A. F. Breslau, Naomi Johnson, Eric O. Hatsukami, Dorothy Pomerleau, Ovide Swan, Gary E. Goate, Alison M. Rutter, Joni Bertelsen, Sarah Fox, Louis Fugman, Douglas Martin, Nicholas G. Montgomery, Grant W. Wang, Jen C. Ballinger, Dennis G. Rice, John P. Bierut, Laura Jean TI Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs SO HUMAN MOLECULAR GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; SEROTONIN TRANSPORTER GENE; CIGARETTE-SMOKING; ACETYLCHOLINE-RECEPTORS; SUBUNIT GENE; BEHAVIOR; SMOKERS; VULNERABILITY; NEUROTICISM; ADDICTION AB Nicotine dependence is one of the world's leading causes of preventable death. To discover genetic variants that influence risk for nicotine dependence, we targeted over 300 candidate genes and analyzed 3713 single nucleotide polymorphisms (SNPs) in 1050 cases and 879 controls. The Fagerstrom test for nicotine dependence (FTND) was used to assess dependence, in which cases were required to have an FTND of 4 or more. The control criterion was strict: control subjects must have smoked at least 100 cigarettes in their lifetimes and had an FTND of 0 during the heaviest period of smoking. After correcting for multiple testing by controlling the false discovery rate, several cholinergic nicotinic receptor genes dominated the top signals. The strongest association was from an SNP representing CHRNB3, the beta 3 nicotinic receptor subunit gene (P = 9.4 x 10(-5)). Biologically, the most compelling evidence for a risk variant came from a non- synonymous SNP in the alpha 5 nicotinic receptor subunit gene CHRNA5 (P = 6.4 x 10(-4)). This SNP exhibited evidence of a recessive mode of inheritance, resulting in individuals having a 2-fold increase in risk of developing nicotine dependence once exposed to cigarette smoking. Other genes among the top signals were KCNJ6 and GABRA4. This study represents one of the most powerful and extensive studies of nicotine dependence to date and has found novel risk loci that require confirmation by replication studies. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Penn State Coll Med, Dept Hlth Evaluat Sci, Hershey, PA 17033 USA. Perlegen Sci, Mountain View, CA 94043 USA. Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. Res Triangle Inst Int, Res Triangle Pk, NC 27709 USA. Univ Minnesota, Dept Psychiat, Minneapolis, MN 55454 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. SRI Int, Hlth Sci Ctr, Menlo Pk, CA 94025 USA. NIDA, Bethesda, MD 20892 USA. Rutgers State Univ, Piscataway, NJ 08854 USA. Queensland Inst Med Res, Brisbane, Qld 4029, Australia. RP Saccone, SF (reprint author), Washington Univ, Sch Med, Dept Psychiat, Box 8134,660 S Euclid Ave, St Louis, MO 63110 USA. EM saccones@msnotes.wustl.edu RI Breslau , Naomi/I-3196-2012; Montgomery, Grant/B-7148-2008; OI Montgomery, Grant/0000-0002-4140-8139; Rutter, Joni/0000-0002-6502-2361; Martin, Nicholas/0000-0003-4069-8020 FU NCI NIH HHS [P01 CA089392-05, P01 CA089392, CA89392]; NIDA NIH HHS [DA015129, DA12854, K01 DA015129, N01DA-0-7079, R01 DA012854, R56 DA012854] NR 46 TC 490 Z9 498 U1 2 U2 19 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 JAN 1 PY 2007 VL 16 IS 1 BP 36 EP 49 DI 10.1093/hmg/ddl438 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 127MY UT WOS:000243591600004 PM 17135278 ER PT J AU Battey, JF AF Battey, James F., Jr. BE Loring, JF Wesselschmidt, RL Schwartz, PH TI Human Stem Cell Manual A Laboratory Guide Foreword SO HUMAN STEM CELL MANUAL: A LABORATORY GUIDE LA English DT Editorial Material; Book Chapter C1 [Battey, James F., Jr.] NIDCD, Bethesda, MD USA. [Battey, James F., Jr.] NIH, Stem Cell Task Force, Bethesda, MD 20892 USA. RP Battey, JF (reprint author), NIDCD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-054988-0 PY 2007 BP IX EP IX DI 10.1016/B978-012370465-8/50000-4 PG 1 WC Cell & Tissue Engineering SC Cell Biology GA BCU13 UT WOS:000311392500001 ER PT J AU Elkareh, J Kennedy, DJ Yashaswi, B Vetteth, S Shidyak, A Kim, EGR Smaili, S Periyasamy, SM Hariri, IM Fedorova, L Liu, J Wu, L Kahaleh, MB Xie, ZJ Malhotra, D Fedorova, OV Kashkin, VA Bagrov, AY Shapiro, JI AF Elkareh, Jihad Kennedy, David J. Yashaswi, Belvadi Vetteth, Sandeep Shidyak, Amjad Kim, Eric G. R. Smaili, Sleiman Periyasamy, Sankaridrug M. Hariri, Imad M. Fedorova, Larisa Liu, Jiang Wu, Liang Kahaleh, M. Bashar Xie, Zijian Malhotra, Deepak Fedorova, Olga V. Kashkin, Vladimir A. Bagrov, Alexei Y. Shapiro, Joseph I. TI Marinobufagenin stimulates fibroblast collagen production and causes fibrosis in experimental uremic cardiomyopathy SO HYPERTENSION LA English DT Article DE cardiomyopathy; renal failure; transforming growth factor (TGF) beta; cardiotonic steroids; reactive oxygen species; fibrosis ID CARDIAC NA+/K+-ATPASE; NA-K PUMP; HEART-FAILURE; ANGIOTENSIN-II; SODIUM-PUMP; OUABAIN; EXPRESSION; RAT; HYPERTROPHY; MYOCYTES AB We have observed recently that experimental renal failure in the rat is accompanied by increases in circulating concentrations of the cardiotonic steroid, marinobufagenin (MBG), and substantial cardiac fibrosis. We performed the following studies to examine whether MBG might directly stimulate cardiac fibroblast collagen production. In vivo studies were performed using the 5/6th nephrectomy model of experimental renal failure (PNx), MBG infusion ( MBG), PNx after immunization against MBG, and concomitant PNx and adrenalectomy. Physiological measurements with a Millar catheter and immunohistochemistry were performed. In vitro studies were then pursued with cultured isolated cardiac fibroblasts. We observed that PNx and MBG increased MBG levels, blood pressure, heart size, impaired diastolic function, and caused cardiac fibrosis. PNx after immunization against MBG and concomitant PNx and adrenalectomy had similar blood pressure as PNx but less cardiac hypertrophy, diastolic dysfunction, and cardiac fibrosis. MBG induced increases in procollagen-1 expression by cultured cardiac fibroblasts at 1 nM concentration. These increases in procollagen expression were accompanied by increases in collagen translation and increases in procollagen-1 mRNA without any demonstrable increase in procollagen-1 protein stability. The stimulation of fibroblasts with MBG could be prevented by administration of inhibitors of tyrosine phosphorylation, Src activation, epidermal growth factor receptor transactivation, and N-acetyl cysteine. Based on these findings, we propose that MBG directly induces increases in collagen expression by fibroblasts, and we suggest that this may be important in the cardiac fibrosis seen with experimental renal failure. C1 Univ Toledo, Coll Med, Dept Med, Toledo, OH 43614 USA. Univ Toledo, Coll Med, Dept Pharmacol, Toledo, OH 43614 USA. NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Shapiro, JI (reprint author), Univ Toledo, Coll Med, Dept Med, 3120 Glendale Ave, Toledo, OH 43614 USA. EM joseph.shapiro@utoledo.edu OI Kashkin, Vladimir/0000-0002-7202-0233 FU Intramural NIH HHS; NHLBI NIH HHS [HL67963] NR 30 TC 71 Z9 74 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2007 VL 49 IS 1 BP 215 EP 224 DI 10.1161/01.HYP.0000252409.36927.05 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127PJ UT WOS:000243598500038 PM 17145984 ER PT B AU Balasubramanian, D Krishna, MC Murugesan, R AF Balasubramanian, D. Krishna, Murali C. Murugesan, R. BE Arivazhagan, S Selvaraj, H Verma, B DeCarvalho, A TI Convolution-based interpolation kernels for reconstruction of high resolution EMR images from low sampled k-space data SO ICCIMA 2007: INTERNATIONAL CONFERENCE ON COMPUTATIONAL INTELLIGENCE AND MULTIMEDIA APPLICATIONS, VOL III, PROCEEDINGS LA English DT Proceedings Paper CT 7th International Conference on Computational Intelligence and Multimedia Applications CY DEC 13-15, 2007 CL Sivakasi, INDIA AB Electron magnetic resonance imaging (EMRI) is an emerging non-invasive imaging technology for mapping free radicals in biological systems. Unlike MRI, it is implemented as a pure phase-phase encoding technique. The fast bio-clearance of the imaging agent and the requirement to reduce radio frequency power deposition dictate collection of reduced k-space samples, compromising the quality and resolution of the EMR images. The present work evaluates various interpolation kernels to generate larger k-space samples for image reconstruction, from the acquired reduced k-space samples. Using k-space EMR data sets, acquired for phantom as well as live mice the proposed technique is critically evaluated by computing quality metrics viz. signal-to-noise ratio (SNR), standard deviation (STD), root mean square error (RMSE), peak signal to noise ratio (PSNR), contrast to noise ratio (CNR) and Lui's error fucntion (F(I)). The quantitative evaluation of 24 different interpolation functions (including piecewise polynomial functions and many windowed sine functions) to upsample the k-space data for Fourier EMR image reconstruction shows that at the expense of a slight increase in computing time, the reconstructed images from upsampled data, produced using Spline-sinc, Welch-sinc and Gaussian-sinc kernels are closer to reference image with lesser distortion. C1 [Balasubramanian, D.] AGP Coll, Sivakasi, India. [Krishna, Murali C.] Natl Canc Inst, Bethesda, MD USA. [Murugesan, R.] MK Univ, Madurai, Tamil Nadu, India. RP Balasubramanian, D (reprint author), AGP Coll, Sivakasi, India. EM dbsmn@yahoo.com; murali@helix.nih.gov; rammku@eth.net FU UGC sponsored center for potential in genomic science program FX Support from the Department of Science and Technology, New Delhi as a major research grant is gratefully acknowledged. A part of this work was carried out under the UGC sponsored center for potential in genomic science program. DB sincerely thanks the Principal and Correspondent of AGP College for encouragement and support throughout this research work. NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA PY 2007 BP 308 EP + DI 10.1109/ICCIMA.2007.80 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BHI34 UT WOS:000253414300056 ER PT B AU Murugesan, R Krishna, MC Alli, P AF Murugesan, R. Krishna, Murali C. Alli, P. BE Arivazhagan, S Selvaraj, H Verma, B DeCarvalho, A TI Adaptive fuzzy control approach for enhancement of electron magnetic resonance tomograms SO ICCIMA 2007: INTERNATIONAL CONFERENCE ON COMPUTATIONAL INTELLIGENCE AND MULTIMEDIA APPLICATIONS, VOL III, PROCEEDINGS LA English DT Proceedings Paper CT 7th International Conference on Computational Intelligence and Multimedia Applications CY DEC 13-15, 2007 CL Sivakasi, INDIA AB Electron magnetic resonance imaging (EMRI), a technique akin to MRI, is fast emerging as a functional imaging modality. But, the poor SNR, originating from the low frequency operation of the EMRI scanner as well as the toxicity-limited dose of the exogenously administrated imaging agents, has hindered the development of EMRI to a viable biomedical technology. Hence novel image enhancement techniques are in need to enhance the potential of EMRI In this paper, we propose one such system based on a fuzzy control filtering approach, using adoptively varying membership Junctions and incorporating fuzzy associative memory (FAM) with conventional multilevel median filter (MLMF). The performance of the system is tested using in vivo EMR images, acquired from a continuous wave (CW) radio frequency (RF) EMR imager and is evaluated visually as well as by computing quantitative metrics such as root mean square error (RMSE) and peak signal to noise ratio (PSNR). Visual and quantitative evaluation show fuzzy filters, especially the one with a new parabolic membership function, to outperform the conventional MLMF method. C1 [Murugesan, R.] Madurai Kamaraj Univ, Madurai 625021, Tamil Nadu, India. [Krishna, Murali C.] Natl Canc Inst, Bethesda, MD USA. [Alli, P.] Avinashilingam Univ, Coimbatore, Tamil Nadu, India. RP Murugesan, R (reprint author), Madurai Kamaraj Univ, Madurai 625021, Tamil Nadu, India. EM rammku@eth.net; murali@helix.nih.gov; alli_rajus@yahoo.com FU UGC sponsored center for potential in genomic science program FX Support from the Department of Science and Technology, New Delhi as a major research grant is gratefully acknowledged. A part of this work was carried out under the UGC sponsored center for potential in genomic science program. Alli sincerely thanks the management of Avinashilingam University for Women, Coimbatore for encouragement and support throughout this research work. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA PY 2007 BP 349 EP + DI 10.1109/ICCIMA.2007.210 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BHI34 UT WOS:000253414300063 ER PT B AU Sumathi, M Krishna, MC Murugesan, R AF Sumathi, M. Krishna, Murali C. Murugesan, R. BE Arivazhagan, S Selvaraj, H Verma, B DeCarvalho, A TI Evolutionary Computational approach for artifact-free image reconstruction from reduced samples: Application to Fourier EMRI SO ICCIMA 2007: INTERNATIONAL CONFERENCE ON COMPUTATIONAL INTELLIGENCE AND MULTIMEDIA APPLICATIONS, VOL III, PROCEEDINGS LA English DT Proceedings Paper CT 7th International Conference on Computational Intelligence and Multimedia Applications CY DEC 13-15, 2007 CL Sivakasi, INDIA ID GENETIC ALGORITHMS; TRANSFORM AB Electron magnetic resonance imaging (EMRI) is emerging as a potential biomedical-imaging technology for noninvasive imaging of free radicals in biological systems. EAMI by single point imaging (SPI) modality is a Fourier imaging technique. The bioclearance of the imaging agent as well as the need to minimize the radio frequency (RF) power deposition on the live animals, dictate reduced k-space sampling. This leads to ringing (Gibbs) artifacts which are severe and seen in both directions of the 2D image, because, unlike the conventional MRI SPI is phase encoding in both directions. To dampen the high frequency components, data tapering windows are multiplicatively applied to provide tolerable blurred resultant image with reduced Gibbs ringing. To find a compromise between blur and ringing artifact, in this paper a method of optimizing the window functions by using genetic algorithm (GA) is proposed. The proposed algorithm is validated, using Matlab codes, first reconstructing AM image of Shepp Logan head phantom from simulated k-space data, and next tested by reconstructing real EMR images of phantoms and live mice from experimentally acquired k-space data. Image quality metrics viz. signal to noise ratio (SNR), contrast to noise ratio (CNR), peak signal to noise ratio (PSNR), root mean square error (RMSE), standard deviation (STD) and the Liu's error function F(I) are computed Our experiments suggest GA-based Kaiser window provides good optimal blur/ringing compromise in EMR tomograms. C1 [Sumathi, M.] Sri Meenakshi Govt, Coll W, Madurai, Tamil Nadu, India. [Krishna, Murali C.] NCI, Bethesda, MD 20892 USA. [Murugesan, R.] MK Univ, Madurai, Tamil Nadu, India. RP Sumathi, M (reprint author), Sri Meenakshi Govt, Coll W, Madurai, Tamil Nadu, India. EM sumothivasagam@gmail.com; murali@helix.nih.gov; rammkti@eth.net FU Department of Science and Technology, New Delhi; UGC; Sri Meenakshi Government College for Women, Madurai FX Support from the Department of Science and Technology, New Delhi as a major research grant is gratefully acknowledged. A part of this work was carried out under the UGC sponsored center for potential in genomic science program. Sumathi sincerely thanks UGC and Sri Meenakshi Government College for Women, Madurai, for the award of a teacher fellowship. NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA PY 2007 BP 464 EP + DI 10.1109/ICCIMA.2007.167 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BHI34 UT WOS:000253414300082 ER PT B AU Chen, SY Mao, S Thorna, GR AF Chen, Siyuan Mao, Song Thorna, George R. BE Werner, B TI Simultaneous layout style and logical entity recognition in a heterogeneous collection of documents SO ICDAR 2007: NINTH INTERNATIONAL CONFERENCE ON DOCUMENT ANALYSIS AND RECOGNITION, VOLS I AND II, PROCEEDINGS LA English DT Proceedings Paper CT 9th International Conference on Document Analysis and Recognition CY SEP 23, 2007-SEP 26, 2009 CL Curitiba, BRAZIL SP Int Assoc Pattern Recognit TC 10, Int Assoc Pattern Recognit TC 11 AB Logical entity recognition in heterogeneous collections of document page images remains a challenging problem since the performance of traditional supervised methods degrades dramatically in case of many distinct layout styles. In this paper we present an unsupervised method where layout style information is explicitly used in both training and recognition phases. We represent the layout style, local features, and logical labels of physical regions of a document compactly by an ordered labeled X-Y tree. Style dissimilarity of two document pages is represented by the distance between their respective trees. During the training phase, document pages with true logical labels in training set are classified into distinct layout styles by unsupervised clustering. During the recognition phase, the layout style and logical entities of an input document are recognized simultaneously by matching the input tree to the trees in closest-matched layout style cluster of training set. Experimental results show that our algorithm is robust with both balanced and unbalanced style cluster sizes, zone over-segmentation, zone length variation, and variation in tree representations of the same layout style. C1 [Chen, Siyuan; Mao, Song; Thorna, George R.] US Natl Lib Med, Bethesda, MD 20894 USA. RP Chen, SY (reprint author), US Natl Lib Med, Bethesda, MD 20894 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-2822-9 PY 2007 BP 118 EP 122 PG 5 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BHC21 UT WOS:000252162600024 ER PT B AU Senf, AJ Leonard, C DeLeo, J AF Senf, Alexander J. Leonard, Carl DeLeo, James BE Wani, MA Kantardzic, MM Li, T Liu, Y Kurgan, L Ye, J Ogihara, M Sagiroglu, S Chen, XW Peterson, L Hafeez, K TI A statistical algorithm to discover knowledge in medical data sources SO ICMLA 2007: SIXTH INTERNATIONAL CONFERENCE ON MACHINE LEARNING AND APPLICATIONS, PROCEEDINGS LA English DT Proceedings Paper CT 6th International Conference on Machine Learning and Applications CY DEC 13-15, 2007 CL Cincinnati, OH SP Assoc Machine Learning & Applicat, IEEE DE clustering methods; pattern recognition; unsupervised learning; feature extraction AB Developing intelligent tools to extract information from data collections has long been of critical importance in fields such as knowledge discovery, information retrieval, pattern recognition, and databases. With the advent of electronic medical records and medical data repositories there is new potential to apply these techniques to the analysis of biomedical data sets. Looking for complex patterns within large biomedical data repositories and discovering previously unexpected associations can be of particular interest for understanding the physiology and functionality of the human body as well as tracing the roots of diseases. In the context of a research hospital these analyses may lead to further directed research, better diagnostic capabilities, and improved patient outcomes. This paper describes an implementation of a knowledge discovery algorithm aimed at such data sets. C1 [Senf, Alexander J.] Univ Kansas, Lawrence, KS 66045 USA. [Leonard, Carl; DeLeo, James] Natl Inst Hlth, Bethesda, MD 20892 USA. RP Senf, AJ (reprint author), Univ Kansas, Lawrence, KS 66045 USA. EM ajsenf@ku.edu; Carl.Leonard@nih.hhs.gov; JamesDeLeo@nih.hhs.gov OI Senf, Alexander/0000-0001-6910-7306 NR 10 TC 0 Z9 0 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3069-7 PY 2007 BP 537 EP + DI 10.1109/ICMLA.2007.91 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BHF84 UT WOS:000252793400087 ER PT J AU Lasker, K Dror, O Shatsky, M Nussinov, R Wolfson, HJ AF Lasker, Keren Dror, Oranit Shatsky, Maxim Nussinov, Ruth Wolfson, Haim J. TI EMatch: Discovery of high resolution structural homologues of protein domains in intermediate resolution cryo-EM maps SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS LA English DT Article; Proceedings Paper CT 5th International Workshop on Algorithms in Bioinformatics (WABI 2005) CY OCT 03-06, 2005 CL Mallorca, SPAIN DE structural bioinformatics; intermediate resolution cryo-EM maps; 3D alignment of secondary structures; macromolecular assemblies; cyclic symmetry ID ELECTRON-DENSITY MAPS; CRYOELECTRON MICROSCOPY; INFORMATICS APPROACH; ANGSTROM RESOLUTION; BETA-SHEETS; RECONSTRUCTIONS; CRYOMICROSCOPY; MACHINES; DATABASE; DOCKING AB Cryo-EM has become an increasingly powerful technique for elucidating the structure, dynamics, and function of large flexible macromolecule assemblies that cannot be determined at atomic resolution. However, due to the relatively low resolution of cryo-EIM data, a major challenge is to identify components of complexes appearing in cryo-EM maps. Here, we describe EMatch, a novel integrated approach for recognizing structural homologues; of protein domains present in a 6-10 angstrom resolution cryo-EM map and constructing a quasi-atomic structural model of their assembly. The method is highly efficient and has been successfully validated on various simulated data. The strength of the method is demonstrated by a domain assembly of an experimental cryo-EM map of native GroEL at 6 angstrom resolution. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res Nanobiol Program, SAIC Frederick,Basic Res Program, Frederick, MD 21702 USA. RP Lasker, K (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM kerenl@post.tau.ac.il; oranit@post.tau.ac.il; maxshats@post.tau.ac.il; ruthnu@post.tau.ac.il; wolfson@post.tau.ac.il RI Wolfson, Haim/A-1837-2011 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 44 TC 18 Z9 18 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1545-5963 J9 IEEE ACM T COMPUT BI JI IEEE-ACM Trans. Comput. Biol. Bioinform. PD JAN-MAR PY 2007 VL 4 IS 1 BP 28 EP 39 DI 10.1109/TCBB.2007.1003 PG 12 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Biochemistry & Molecular Biology; Computer Science; Mathematics GA 142JJ UT WOS:000244645300005 PM 17277411 ER PT J AU Stafford, P Chen, YD AF Stafford, Phillip Chen, Yidong TI Expression technology SO IEEE SIGNAL PROCESSING MAGAZINE LA English DT Review ID GENE-EXPRESSION; OLIGONUCLEOTIDE ARRAYS; BREAST-CANCER; DNA; MICROARRAYS C1 Arizona State Univ, Tempe, AZ 85287 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Stafford, P (reprint author), Arizona State Univ, Tempe, AZ 85287 USA. EM yidong@mail.nih.gov RI Magazine, Signal Processing/E-9947-2015 NR 30 TC 3 Z9 3 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1053-5888 J9 IEEE SIGNAL PROC MAG JI IEEE Signal Process. Mag. PD JAN PY 2007 VL 24 IS 1 BP 18 EP 26 DI 10.1109/MSP.2007.273050 PG 9 WC Engineering, Electrical & Electronic SC Engineering GA 117IM UT WOS:000242866600004 ER PT S AU Subramanian, S Devasahayam, N Krishna, MC AF Subramanian, Sankaran Devasahayam, Nallathamby Krishna, M. C. BE Farkas, DL Leif, RC Nicolau, DV TI Radiofrequency time-domain EPR imaging: Instrumentation development and recent results in functional physiological in vivo imaging - art. no. 644106 SO Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V CY JAN 22-24, 2007 CL San Jose, CA SP SPIE DE time-domain EPR; FT_EPR; imaging; oxymetry; free radicals; functional imaging; tumor hypoxia ID ELECTRON-PARAMAGNETIC-RESONANCE; HIGH-RESOLUTION NMR; MAGNETIC-RESONANCE; LITHIUM PHTHALOCYANINE; FREE-RADICALS; CONTINUOUS-WAVE; ELECTROCHEMICAL PREPARATION; LOW-FREQUENCY; NITRIC-OXIDE; FT EPR AB Electron Paramagnetic Resonance is an emerging technique finding applications in functional physiological imaging. Traditionally EPR imaging developed as a CW (continuous wave) technique involving the measurement of free radical distribution in vivo using constant frequency and field-sweep modality almost identical to the early developments of MRI. As in CT and PET this involved the generation of projections in presence of gradients and the reconstruction of images via filtered back-projection. The large line-width and the concomitant short relaxation times posed a serious challenge for the development of time-domain methods akin to modem pulsed NMR & MRI. With the recent availability of narrow line stable non-toxic radicals based on triarylmethyl (TAM), ultra fast data acquisition systems (signal digitizer and summer), very fast electronic switches and low-noise amplifiers, we have developed time-domain imaging schemes in EPR operating in the radiofrequency region Using a novel pure-phase encoding scheme, we are able to generate 2 and 3 dimensional spatial images and spectral-spatial images that adds an additional functional dimension to these images. The special space-encoding scheme with fast gradient ramping allow rapid in vivo imaging of small animals with superior spatial and functional information with good temporal resolution that can provide valuable physiological and pharmacokinetic insight. Our main thrust has been in the investigation of tumor hypoxia and tumor reoxygenation for the purpose of minimizing the radiation dose for maximum tumor cell killing. These and some of the allied imaging methods, and results from tumor investigation will be presented. C1 NCI, NIH, Radiat Biol Branch, CCR, Bethesda, MD 20892 USA. RP Subramanian, S (reprint author), NCI, NIH, Radiat Biol Branch, CCR, Bethesda, MD 20892 USA. NR 83 TC 0 Z9 0 U1 1 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6554-2 J9 P SOC PHOTO-OPT INS PY 2007 VL 6441 BP 44106 EP 44106 AR 644106 DI 10.1117/12.700928 PG 17 WC Engineering, Biomedical; Instruments & Instrumentation; Microscopy; Optics; Imaging Science & Photographic Technology SC Engineering; Instruments & Instrumentation; Microscopy; Optics; Imaging Science & Photographic Technology GA BGA94 UT WOS:000245855200004 ER PT S AU Gudla, PR Collins, J Meaburn, KJ Misteli, T Lockett, SJ AF Gudla, Prabhakar R. Collins, J. Meaburn, K. J. Misteli, T. Lockett, S. J. BE Farkas, DL Leif, RC Nicolau, DV TI HiFLO - A high-throughput system for spatial analysis of FISH loci in interphase nuclei - art. no. 644119 SO Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues V CY JAN 22-24, 2007 CL San Jose, CA SP SPIE DE high-throughput image analysis; cluster analysis; watershed; region-merging; non-uniform illumination; fluorescent in situ hybridization; genomic organization ID TISSUE-SECTIONS; CELL-NUCLEI; SEGMENTATION; IMAGE; SELECTION AB Numerous investigations in the last years focused on chromosome and gene arrangements through the application of statistical methods that analyze the non randomness of spatial distributions of fluorescence in situ hybridization (FISH) labeled nucleic acid sequences in terms of their distance to the nuclear centers and their proximity to each other. However, existing imaging processing methods are rather limited in extracting sufficient number of nuclei with FISH label sequences, and manual analysis is unreasonably time-consuming and subjective. This paper presents an automated system that integrates a series of advanced image processing methods to over come this rate-limiting step. Evaluation results show that the proposed method is efficient, robust, and effective in extracting individual nuclei with FISH labels. C1 SAIC Frederick, NCI, Image Analysis Lab, Frederick, MD 21702 USA. RP Gudla, PR (reprint author), SAIC Frederick, NCI, Image Analysis Lab, 1050 Boyles St, Frederick, MD 21702 USA. OI Meaburn, Karen/0000-0002-1327-5957 NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-6554-2 J9 P SOC PHOTO-OPT INS PY 2007 VL 6441 BP 44119 EP 44119 AR 644119 DI 10.1117/12.700817 PG 9 WC Engineering, Biomedical; Instruments & Instrumentation; Microscopy; Optics; Imaging Science & Photographic Technology SC Engineering; Instruments & Instrumentation; Microscopy; Optics; Imaging Science & Photographic Technology GA BGA94 UT WOS:000245855200036 ER PT S AU Shanker, A Sayers, T AF Shanker, Anil Sayers, Thomas BE Shurin, MR Smolkin, YS TI Sensitizing tumor cells to immune-mediated cytotoxicity SO IMMUNE-MEDIATED DISEASES: FROM THEORY TO THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Immune-Mediated Diseases Congress CY OCT 03-08, 2005 CL Moscow, RUSSIA ID EFFECTOR T-CELLS; ADOPTIVE IMMUNOTHERAPY; PROTEASOME INHIBITION; CANCER-THERAPY; IN-VITRO; PERFORIN; REGRESSION; APOPTOSIS; APO2L/TRAIL; CARCINOMA AB The molecular basis underlying tumor destruction in vivo by specific antitumor CD8(+) T cells remains unclear. We propose that the local production of certain tumor necrosis factor (TNF)-family members (death ligands) may be more important for tumor destruction in vivo than previously thought. Also, the apoptotic response of some tumor cells to the TNF-family member TRAIL can be augmented by the proteasome inhibitor bortezomib (Velcade). Thus, bortezomib may sensitize tumor cells to T cell-mediated cytotoxicity and could potentially improve the beneficial effects of immunotherapy. C1 NCI, SAIC Frederick Inc, Canc & Inflammat Program, Frederick, MD 21701 USA. RP Sayers, T (reprint author), NCI, SAIC Frederick Inc, Canc & Inflammat Program, Frederick, MD 21701 USA. EM sayerst@mail.nih.gov RI Sayers, Thomas/G-4859-2015; OI Shanker, Anil/0000-0001-6372-3669 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 18 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-72004-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 601 BP 163 EP 171 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BGN45 UT WOS:000248597900017 PM 17713003 ER PT S AU Oppenheim, JJ Tewary, P de la Rosa, G Yang, D AF Oppenheim, Joost J. Tewary, Poonarn de la Rosa, Gonzalo Yang, De BE Shurin, MR Smolkin, YS TI Alarmins initiate host Defense SO IMMUNE-MEDIATED DISEASES: FROM THEORY TO THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Immune-Mediated Diseases Congress CY OCT 03-08, 2005 CL Moscow, RUSSIA ID EOSINOPHIL-DERIVED NEUROTOXIN; HUMAN DENDRITIC CELLS; ANTIMICROBIAL ACTIVITY; CHEMOTACTIC ACTIVITIES; HUMAN BETA-DEFENSIN-3; IMMUNE ADJUVANT; INNATE IMMUNITY; RECEPTOR; PEPTIDE; ACTIVATION AB In response to infection and/or tissue injury, cells of the host innate immune system rapidly produce a variety of structurally distinct mediators (we elect to call alarmins) that not only function as potent effectors of innate defense but also act to alarm the immune system by promoting the recruitment and activation of host leukocytes through interaction with distinct receptors. Alarmins are capable of activating antigen-presenting cells (APCs) and enhancing the development of antigen-specific immune responses. Here, we discuss the characteristics of several alarmins, a variety of potential alarmin candidates and potential implications of alarmins. C1 NCI, Lab Mol Immunoregulat, Canc Res Ctr, Frederick, MD 21701 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. RP Oppenheim, JJ (reprint author), NCI, Lab Mol Immunoregulat, Canc Res Ctr, Frederick, MD 21701 USA. EM Oppenhei@ncifcrf.gov FU Intramural NIH HHS NR 42 TC 108 Z9 112 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-72004-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 601 BP 185 EP 194 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BGN45 UT WOS:000248597900019 PM 17713005 ER PT S AU Malyguine, A Strobl, S Zaritskaya, L Baseler, M Shafer-Weaver, K AF Malyguine, Anatoli Strobl, Susan Zaritskaya, Liubov Baseler, Michael Shafer-Weaver, Kimberly BE Shurin, MR Smolkin, YS TI New approaches for monitoring CTL activity in clinical trials SO IMMUNE-MEDIATED DISEASES: FROM THEORY TO THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Immune-Mediated Diseases Congress CY OCT 03-08, 2005 CL Moscow, RUSSIA ID NATURAL-KILLER-CELLS; B ELISPOT ASSAY; GRANZYME-B; T-LYMPHOCYTES; MELANOMA PATIENTS; IMMUNE-RESPONSE; IFN-GAMMA; TUMOR; PERFORIN; PEPTIDE AB We have developed a modification of the ELISPOT assay that measures Granzyme B (GrB) release from cytotoxic T lymphocytes (CTLs). The GrB ELISPOT assay is a superior alternative to the Cr-51-release assay since it is significantly more sensitive and provides an estimation of cytotoxic effector cell frequency. Additionally, unlike the IFN-gamma ELISPOT assay, the GrB ELISPOT directly measures the release of a cytolytic protein. We report that the GrB ELISPOT can be utilized to measure ex vivo antigen-specific cytotoxicity of peripheral blood mononuclear cells (PBMCs) from cancer patients vaccinated with a peptide-based cancer vaccine. We compare the reactivity of patients' PBMCs in the GrB ELISPOT, with reactivity in the tetramer, IFN-gamma ELISPOT and chromium (Cr-51)-release assays. Differences in immune response over all assays tested were found between patients, and four response patterns were observed. Reactivity in the GrB ELISPOT was more closely associated with cytotoxicity in the Cr-51-release assay than the tetramer or IFN-gamma ELISPOT assays. We also optimized the GrB ELISPOT assay to directly measure immune responses against autologous primary tumor cells in vaccinated cancer patients. A perform ELISPOT assay was also adapted to evaluate peptide-stimulated reactivity of PMBCs from vaccinated melanoma patients. Modifications of the ELISPOT assay described in this chapter allow a more comprehensive evaluation of low-frequency tumor-specific CTLs and their specific effector functions and can provide a valuable insight into immune responses in cancer vaccine trials. C1 NCI, SAIC Frederick Inc, Appl & Dev Res Support Program, Frederick, MD 21701 USA. RP Malyguine, A (reprint author), NCI, SAIC Frederick Inc, Appl & Dev Res Support Program, Frederick, MD 21701 USA. EM amalyguine@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 38 TC 23 Z9 25 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-72004-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 601 BP 273 EP 284 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BGN45 UT WOS:000248597900029 PM 17713015 ER PT S AU Fleisher, TA AF Fleisher, Thomas A. BE Shurin, MR Smolkin, YS TI Evaluation of suspected immunodeficiency SO IMMUNE-MEDIATED DISEASES: FROM THEORY TO THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Immune-Mediated Diseases Congress CY OCT 03-08, 2005 CL Moscow, RUSSIA ID FLOW-CYTOMETRY; T-CELLS; DISORDERS; ANTIBODY; DEFICIENCIES; PHENOTYPE; DISEASES AB The clinical utility and capacity to evaluate immunologic function has evolved significantly over the past few decades. This chapter summarizes screening methods and more sophisticated approaches to assess the immune system when there is a suspicion of an immune deficiency. C1 NIH, Dept Lab Med, NIH Clin Ctr, DHHS, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIH, Dept Lab Med, NIH Clin Ctr, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM tfleisher@mail.nih.gov NR 26 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-72004-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 601 BP 291 EP 300 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BGN45 UT WOS:000248597900031 PM 17713017 ER PT S AU Sportes, C Gress, RE AF Sportes, Claude Gress, Ronald E. BE Shurin, MR Smolkin, YS TI Interleukin-7 immunotherapy SO IMMUNE-MEDIATED DISEASES: FROM THEORY TO THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Immune-Mediated Diseases Congress CY OCT 03-08, 2005 CL Moscow, RUSSIA ID RECEPTOR-DEFICIENT MICE; T-CELL HOMEOSTASIS; B-LINEAGE CELLS; SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW-TRANSPLANTATION; INTENSIVE CHEMOTHERAPY; THYMOCYTE DEVELOPMENT; LYMPHOCYTE DEPLETION; POTENTIAL ROLE; BREAST-CANCER AB IL-7 is a member of the common gamma-chain family of cytokines sharing a common gamma-chain in their receptor. Beyond its long-established pivotal role in immune development, it has been more recently recognized as a critically important regulator of peripheral naive and memory T cell homeostasis while its role in postdevelopment thymic function remains at best, poorly defined, and controversial. Its multiple immune-enhancing properties, most notably in the maintenance of T cell homeostasis, make it a very attractive candidate for immunotherapy in a wide variety of clinical situations. Following many years of rich preclinical data in murine and simian models, IL-7 is now emerging in human phase I trials as a very promising immunotherapeutic agent. Human in vivo data discussed here are derived from the phase I study initiated at the National Cancer Institute in collaboration with Cytheris, Inc., in a cohort of subjects with incurable malignancy. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Sportes, C (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. EM csportes@mail.nih.gov NR 56 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-72004-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 601 BP 321 EP 333 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BGN45 UT WOS:000248597900035 PM 17713021 ER PT S AU Shafer-Weaver, K Anderson, M Malyguine, A Hurwitz, AA AF Shafer-Weaver, Kimberly Anderson, Michael Malyguine, Anatoli Hurwitz, Arthur A. BE Shurin, MR Smolkin, YS TI T cell tolerance to tumors and cancer immunotherapy SO IMMUNE-MEDIATED DISEASES: FROM THEORY TO THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Immune-Mediated Diseases Congress CY OCT 03-08, 2005 CL Moscow, RUSSIA ID APOPTOSIS-INDUCING LIGAND; MYELOID SUPPRESSOR-CELLS; GROWTH-FACTOR-BETA; PROSTATE-CANCER; DENDRITIC CELLS; IN-VIVO; COMBINATION IMMUNOTHERAPY; LYMPHOCYTE RESPONSES; COLORECTAL-CANCER; TRANSGENIC MOUSE AB It is widely recognized that the immune system plays a role in cancer progression and that some tumors are inherently immunogenic. The identification of tumor-associated antigens (TAAs) has stimulated research focused on immunotherapies to mediate the regression of established tumors. Cancer-specific immunity has traditionally been aimed at activating CD8(+) cytotoxic T lymphocytes (CTLs) directed against major histocompatibility complex (MHC) class I-binding peptide epitopes. Other approaches utilize T cell adoptive therapy where autologous, tumor-specific T cells propagated in vitro are transferred back into recipients. However, these strategies have met with limited success in part due to the regulatory mechanisms of T cell tolerance, which poses a considerable challenge to cancer immunotherapy. Our laboratory utilizes the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, a murine model of prostate cancer, to study mechanisms of T cell tolerization to tumor antigens. We previously demonstrated that upon encounter with their cognate antigen in the tumor microenvironment, naive T cell become tolerized. Our ongoing studies are testing whether provision of CD4(+) T cells can enhance tumor immunity by preventing CD8(+) T cell tolerance. A greater understanding of the interaction between various tumor-specific T cell subsets will facilitate the design of novel approaches to stimulate a more potent antitumor immune response. C1 NCI, SAIC Frederick Inc, Appl & Dev Res Support Program, Frederick, MD 21701 USA. NIH, Tumor Immun & Tolerance Sect, Lab Mol Immunoregulat, Canc & Inflammat Program,CCR, Frederick, MD USA. RP Shafer-Weaver, K (reprint author), NCI, SAIC Frederick Inc, Appl & Dev Res Support Program, Frederick, MD 21701 USA. EM hurwitza@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 62 TC 11 Z9 11 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-72004-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2007 VL 601 BP 357 EP 368 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BGN45 UT WOS:000248597900038 PM 17713024 ER PT J AU Smirnova, AS Ferreira-Silva, KC Mine, KL Andrade-Oliveira, V Shulzhenko, N Gerbase-DeLima, M Morgun, A AF Smirnova, Anna S. Ferreira-Silva, Katia C. Mine, Karina L. Andrade-Oliveira, Vinicius Shulzhenko, Natalia Gerbase-DeLima, Maria Morgun, Andrey TI A novel strategy for defining haplotypes by selective depletion using restriction enzymes SO IMMUNOGENETICS LA English DT Article DE haplotype; polymorphism; restriction enzyme; selective depletion; lymphotoxin alpha; LTA ID TUMOR-NECROSIS-FACTOR; DEPENDENT DIABETES-MELLITUS; FACTOR TNF; LINKAGE DISEQUILIBRIUM; ALPHA; BETA; POLYMORPHISMS; ALLELES; GENE; ASSOCIATION AB Various single nucleotide polymorphisms (SNPs) have been investigated regarding association with gene expression levels or human diseases. Although different SNPs within one gene are frequently analyzed individually, it is highly probable that in the majority of the cases, a precise combination of SNP alleles, i.e., haplotype, determines a functional trait. Methods commonly used for haplotype determination, involving studies in families, cloning, or somatic cell hybrids, are expensive and time-consuming. We herein suggest a novel and simple strategy for haplotype determination, involving selective haplotype depletion with a restriction enzyme, followed by sequencing. We studied 11 LTA gene polymorphisms in 102 Brazilian individuals, and we applied this novel methodology for haplotyping 67 out of 70 LTA heterozygous individuals. We concluded that the method is rapid and efficient, and, as it includes only simple and widespread-used techniques, it could be used in most of the laboratories without further investment in equipments. The wider usage of haplotyping could be important to clarify contradictory results frequently observed among studies that focus on a single SNP. C1 Univ Fed Sao Paulo, Dept Pediat, Div Immunogenet, UNIFESP,EPM, BR-04040031 Sao Paulo, Brazil. NIAID, LCMI, NIH, Bethesda, MD 20892 USA. RP Smirnova, AS (reprint author), Univ Fed Sao Paulo, Dept Pediat, Div Immunogenet, UNIFESP,EPM, Rua Loefgreen 1235, BR-04040031 Sao Paulo, Brazil. EM annsmile141@yahoo.com RI Andrade-Oliveira, Vinicius/K-4146-2012; Gerbase-DeLima, Maria/K-2515-2015; Smirnova, Anna/E-5859-2016 OI Andrade-Oliveira, Vinicius/0000-0002-0426-1828; NR 25 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JAN PY 2007 VL 59 IS 1 BP 93 EP 98 DI 10.1007/s00251-006-0172-8 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 119GP UT WOS:000243001100010 PM 17146685 ER PT J AU Metzger, H AF Metzger, Henry TI Good memories SO IMMUNOLOGIC RESEARCH LA English DT Biographical-Item C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Metzger, H (reprint author), NIAMSD, NIH, Rm 10S259,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. EM metzgerh@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2007 VL 38 IS 1-3 BP 137 EP 138 DI 10.1007/s12026-007-0046-7 PG 2 WC Immunology SC Immunology GA 223LQ UT WOS:000250372300018 ER PT J AU Holland, SM AF Holland, Steven M. TI Interferon gamma, IL-12, IL-12R and STAT-1 immunodeficiency diseases: disorders of the interface of innate and adaptive immunity SO IMMUNOLOGIC RESEARCH LA English DT Article; Proceedings Paper CT 1st Robert-A-Good-Society Symposium CY 2006 CL St Petersburg, FL SP Robert A Good Soc DE mycobacteria; salmonella; tuberculosis; dominant; recessive ID PULMONARY ALVEOLAR PROTEINOSIS; DEFICIENCY; INFECTIONS; DOMINANT; CONSEQUENCES; DELETION AB Susceptibility to mycobacterial infection has long been associated with defects in T cell immunity, such as those conferred by HIV infection or iatrogenic immune suppression. However, despite these well-recognized predispositions to clinical disease with tuberculosis and nontuberculous mycobacteria, the genetic disorders that are relatively specific for mycobacterial infection with nontuberculous bacteria and bacille Calmette Guerin (BCG) involve the innate immune pathways, and all engage interferon Gamma and IL-12 production, signaling, and availability. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov NR 15 TC 32 Z9 34 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2007 VL 38 IS 1-3 BP 342 EP 346 DI 10.1007/s12026-007-0045-8 PG 5 WC Immunology SC Immunology GA 223LQ UT WOS:000250372300038 PM 17917041 ER PT J AU Stewart, DM Tian, L Notarangelo, LD Nelson, DL AF Stewart, Donn M. Tian, Lan Notarangelo, Luigi D. Nelson, David L. TI X-linked hypogammaglobulinemia and isolated growth hormone deficiency: an update SO IMMUNOLOGIC RESEARCH LA English DT Article; Proceedings Paper CT 1st Robert-A-Good-Society Symposium CY 2006 CL St Petersburg, FL SP Robert A Good Soc DE X-chromosome; hypogammaglobulinemia; growth hormone; B-cells; Bruton's tyrosine kinase; Btk myeloid elf-1-like factor; MEF ID BRUTONS TYROSINE KINASE; TRANSCRIPTION FACTOR; GENE-CLUSTER; BTK GENE; AGAMMAGLOBULINEMIA; PATIENT; PROTEIN; MEF; EXPRESSION AB X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLH-GHD, OMIM # 307200) is a primary immunodeficiency disorder characterized by pan-hypogammaglobulinemia and isolated growth hormone deficiency. The disease, which is only known to occur in a single family, shares many features with X-linked agammaglobulinemia (XLA, OMIM # 300300). The current review summarizes the clinical, laboratory and genetic features of the disease as they have unfolded over the past quarter century since its description. C1 NCI, Immunophysiol Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA USA. Univ Brescia, Spedali Civili, Ist Med Mol Angelo Nocivelli, I-25123 Brescia, Italy. RP Nelson, DL (reprint author), NCI, Immunophysiol Sect, Metab Branch, NIH, Bldg 10,Rm 4N115,MSC 1374, Bethesda, MD 20892 USA. EM dln@helix.nih.gov RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 31 TC 4 Z9 6 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2007 VL 38 IS 1-3 BP 391 EP 399 DI 10.1007/s12026-007-0052-9 PG 9 WC Immunology SC Immunology GA 223LQ UT WOS:000250372300046 PM 17917049 ER PT J AU Zhou, YH Chen, ZC Purcell, RH Emerson, SU AF Zhou, Yi-Hua Chen, Zhaochun Purcell, Robert H. Emerson, Suzanne U. TI Positive reactions on Western blots do not necessarily indicate the epitopes on antigens are continuous SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE SDS-PAGE; immunoblotting; epitope type ID HEPATITIS-E-VIRUS; VP2 LINEAR EPITOPES; ACUTE RESPIRATORY SYNDROME; HUMAN MONOCLONAL-ANTIBODY; B19 PARVOVIRUS VP1; STRUCTURAL PROTEINS; VACCINIA VIRUS; COAT PROTEIN; SARS-COV; IGG AB Epitope mapping (identification of an antigenic site recognized by an antibody) is an important component of vaccine development and immunological assays. It is widely accepted that in Western blots, antibodies react exclusively with continuous epitopes: discontinuous epitopes are assumed to be irreversibly destroyed by electrophoresis under the denaturing conditions used for sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Here, we demonstrate that the epitopes recognized by four different monoclonal antibodies were identified as discontinuous epitopes when characterized by radioimmunoprecipitation assays and enzyme-linked immunosorbent assays, yet each of these antibodies reacted with the corresponding antigen on Western blots. Reaction on Western blots may be due to epitope renaturation during or after the transfer of the protein to a membrane. Therefore, positive reactions on Western blots do not necessarily indicate that epitopes are continuous and this caveat should be kept in mind while characterizing them. C1 NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NIAID, Mol Hepatitis Sect, NIH, Bethesda, MD 20892 USA. RP Zhou, YH (reprint author), NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bldg 50,Room 6535,50 S Dr MSC 8009, Bethesda, MD 20892 USA. EM yzhou@niaid.nih.gov FU Intramural NIH HHS NR 40 TC 20 Z9 21 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JAN PY 2007 VL 85 IS 1 BP 73 EP 78 DI 10.1038/sj.icb.7100004 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 138QL UT WOS:000244377200013 PM 17130902 ER PT B AU Fuss, IJ AF Fuss, I. J. BE Dignass, A Rachmilewitz, D Stange, EF Weinstock, JV TI The adaptive immune responses in inflammatory bowel disease SO Immunoregulation in Inflammatory Bowel Diseases - Current Understanding and Innovation SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 153 on Immunoregulation in Inflammatory Bowel Diseases CY MAY 06-07, 2006 CL Berlin, GERMANY SP Falk Fdn ID ACTIVE CROHNS-DISEASE; NK-T-CELLS; ULCERATIVE-COLITIS; NOD2; ANTIBODY; IL-23; INTERLEUKIN-12; ACTIVATION; MICE C1 NIAID, NIH, Host Def Lab, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Fuss, IJ (reprint author), NIAID, NIH, Host Def Lab, Mucosal Immun Sect, Bldg 10,Room 5-3864, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-5888-2 J9 FALK SYMP PY 2007 VL 153 BP 12 EP 20 PG 9 WC Gastroenterology & Hepatology; Immunology SC Gastroenterology & Hepatology; Immunology GA BGD92 UT WOS:000246214800002 ER PT J AU Samuel, NM Srijayanth, P Dharmarajan, S Bethel, J Van Hook, H Jacob, M Jullankar, V Chamberlin, J Collins, D Read, JS AF Samuel, N. M. Srijayanth, P. Dharmarajan, S. Bethel, J. Van Hook, H. Jacob, M. Jullankar, V. Chamberlin, J. Collins, D. Read, J. S. TI Acceptance of HIV-1 education & voluntary counselling/testing by & seroprevalence of HIV-1 among, pregnant women in rural south India SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Article DE education; HIV-1; India; pregnancy; rapid testing; seroprevalence ID BINOMIAL CONFIDENCE-INTERVALS; TAMIL-NADU; INFECTION; PREVALENCE; HIV/AIDS; DRIVERS; URBAN; AREAS AB Background & objectives: Since the first report of HIV-1 infection in Tamil Nadu, India, HIV-1 seroprevalence in India has increased steadily. Though interventions to prevent mother-to-child transmission (MTCT) are available, their implementation is a significant challenge. Therefore, among pregnant women in rural Tamil Nadu, the acceptance of education regarding HIV-1 infection and transmission and, among a systematic sample, knowledge, attitudes, and beliefs; the acceptance of HIV-1 voluntary counselling and testing (VCT); and the seroprevalence of HIV-1 infection as well as risk factors for seropositivity were assessed. Methods: Pregnant women registered in the antenatal clinics at Namakkal District Hospital and Rasipuram Government Hospital, Tamil Nadu, India, were offered an educational session regarding HIV-1 infection and transmission. HIV-1 VCT, with informed consent, was offered. Positive results with HIV-1 rapid testing were confirmed with HIV-1 ELISA and Western blot assays. With informed consent, a systematic sample of the study population was asked to participate in pre- and post-education assessments. Chi-square tests were used to evaluate HIV-1 risk factors. Results: The educational session as well as VCT were well accepted by rural, pregnant, HIV-1-infected women. Of 3722 women registered for antenatal care at the two hospitals over a one year period, 3691 (99.2%) agreed to participate in the educational session and 3715 (99.8%) had VCT (74 had confirmed HIV-1 infection [seroprevalence: 2.0% (95% confidence interval (95% CI): 1.6%, 2.5%)]). Of 759 eligible women, a systematic sample of 757 (99.7%) women participated in the pre- and post-education assessments. Although baseline knowledge regarding HIV-1 was limited, a highly significant improvement in such knowledge was observed (P < 0.0001 for all comparisons of changes in knowledge, attitudes, and beliefs measured before and immediately after the educational session). The median per cent of correct responses increased from 26.4 per cent before the educational session to 93.8 per cent afterwards. Women whose husbands were long distance truck drivers were at increased risk of HIV-1 infection. Other factors associated with HIV-1 infection were clinical site (Namakkal District Hospital), a smaller number of persons in the household, being unmarried, and a history of previous surgeries. Interpretation & conclusion: The acceptability of education and of VCT among antenatal clinic attendees in this study was encouraging. However, the relatively high seroprevalence highlights the spread of HIV-1 from high risk groups to the general population and emphasizes the need for primary prevention of HIV-1 infection among adolescent girls and women of reproductive age in India. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. Tamil Nadu Dr MGR Med Univ, Madras, Tamil Nadu, India. Westat Corp, Rockville, MD USA. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11F,6100 Execut Blvd MSC 7510, Bethesda, MD 20892 USA. EM JENNIFER-READ@NIH.GOV FU NICHD NIH HHS [1-HD-3-3345] NR 18 TC 16 Z9 17 U1 0 U2 1 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD JAN PY 2007 VL 125 IS 1 BP 49 EP 64 PG 16 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA 148XM UT WOS:000245110700010 PM 17332657 ER PT J AU Mash, C Arterberry, ME Bornstein, MH AF Mash, Clay Arterberry, Martha E. Bornstein, Marc H. TI Mechanisms of visual object recognition in infancy: Five-month-olds generalize beyond the interpolation of familiar views SO INFANCY LA English DT Article ID 3-DIMENSIONAL FORM; MULTIPLE VIEWS; PERCEPTION; SHAPE; COMPONENTS AB This work examined predictions of the interpolation of familiar views (IFV) account of object recognition performance in 5-month-olds. Infants were familiarized to an object either from a single viewpoint or from multiple viewpoints varying in rotation around a single axis. Object recognition was then tested in both conditions with the same object rotated around a novel axis. Infants in the multiple-views condition recognized the object, whereas infants in the single-view condition provided no evidence for recognition. Under the same 2 familiarization conditions, infants in a 2nd experiment treated as novel an object that differed in only I component from the familiar object. Infants' object recognition is enhanced by experience with multiple views, even when that experience is around an orthogonal axis of rotation, and infants are sensitive to even subtle shape differences between components of similar objects. In general, infants' performance does not accord with the predictions of the IFV model of object recognition. These findings motivate the extension of future research and theory beyond the limits of strictly interpolative mechanisms. C1 NICHD, Sect Child & Family Res, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mash, C (reprint author), NICHD, Sect Child & Family Res, NIH, US Dept Hlth & Human Serv, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM mashc@mail.nih.gov NR 26 TC 9 Z9 9 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1525-0008 J9 INFANCY JI Infancy PY 2007 VL 12 IS 1 BP 31 EP 43 PG 13 WC Psychology, Developmental SC Psychology GA 194OI UT WOS:000248353300002 ER PT J AU Bornstein, MH Hendricks, C Haynes, OM Painter, KM AF Bornstein, Marc H. Hendricks, Charlene Haynes, O. Maurice Painter, Kathleen M. TI Maternal sensitivity and child responsiveness: Associations with social context, maternal characteristics, and child characteristics in a multivariate analysis SO INFANCY LA English DT Review ID NATIONAL LONGITUDINAL SURVEY; LOW-BIRTH-WEIGHT; EMOTIONAL AVAILABILITY; HOME-ENVIRONMENT; VOCABULARY COMPETENCE; SELF-EFFICACY; MOTHER; EMPLOYMENT; BEHAVIOR; ACHIEVEMENT AB This study examined unique associations of multiple distal context variables (family socioeconomic status [SES], maternal employment, and paternal parenting) and proximal maternal (personality, intelligence, and knowledge; behavior, self-perceptions, and attributions) and child (age, gender, representation, language, and sociability) characteristics with maternal sensitivity and child responsiveness in 254 European American mothers and their firstborn 20-month-olds. Specific unique relations emerged in hierarchical regression analyses. Mothers who worked fewer hours per week and reported less dissonance in their husbands' didactic parenting, whose children spoke using more vocabulary, and who reported less limit setting in their parenting and attributed their parenting failures to internal causes were observed to be more sensitive in their interactions with their children. Children in higher SES families, whose mothers worked fewer hours and attributed their parenting failures to internal causes, and who themselves used more vocabulary were observed to be more responsive in their interactions with their mothers. Although potential associations are many, when considered together, unique associations with maternal sensitivity and child responsiveness are few, and some are shared whereas others are unique. C1 NICHHD, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, NIH, US Dept HHS, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 147 TC 26 Z9 27 U1 6 U2 34 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1525-0008 J9 INFANCY JI Infancy PY 2007 VL 12 IS 2 BP 189 EP 223 PG 35 WC Psychology, Developmental SC Psychology GA 215XP UT WOS:000249842600004 ER PT J AU Mash, C AF Mash, Clay TI Object representation in infants' coordination of manipulative force SO INFANCY LA English DT Article ID WEIGHT; SHAPE AB This study examined infants' use of object knowledge for scaling the manipulative force of object-directed actions. Infants 9, 12, and 15 months of age were outfitted with motion-analysis sensors on their arms and then presented with stimulus objects to examine individually over a series of familiarization trials. Two stimulus objects were used in the familiarization phase, and were identical in size, shape, and material, but different in color and weight. Following familiarization, two test objects that had been hidden from view were presented. The test objects were identical in appearance to the familiarization objects, but their color-weight correspondence was reversed. Infants' actions on the test objects revealed selective, differential preparation for the specific weights experienced during familiarization. Because the objects were equivalent in their visual affordances for action, the differential preparation and coordination of manipulative force was based on knowledge acquired during the familiarization phase. Infants are capable of utilizing object representations to coordinate manipulative force in object-directed actions. C1 NICHD, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mash, C (reprint author), NICHD, NIH, US Dept Hlth & Human Serv, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM mashc@mail.nih.gov NR 16 TC 10 Z9 10 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1525-0008 J9 INFANCY JI Infancy PY 2007 VL 12 IS 3 BP 329 EP 341 PG 13 WC Psychology, Developmental SC Psychology GA 233QY UT WOS:000251106600005 ER PT J AU Lunemann, JD Gelderblom, H Sospedra, M Quandt, JA Pinilla, C Marques, A Martin, R AF Luenemann, Jan D. Gelderblom, Harald Sospedra, Mireia Quandt, Jacqueline A. Pinilla, Clemencia Marques, Adriana Martin, Roland TI Cerebrospinal fluid-infiltrating CD4(+) T cells recognize Borrelia burgdorferi lysine-enriched protein domains and central nervous system autoantigens in early lyme encephalitis SO INFECTION AND IMMUNITY LA English DT Article ID 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; ALTERED PEPTIDE LIGANDS; INDIVIDUAL AMINO-ACIDS; MYELIN BASIC-PROTEIN; MOLECULAR MIMICRY; CANDIDATE AUTOANTIGEN; MULTIPLE-SCLEROSIS; MEMBRANE-PROTEINS; IFN-GAMMA; NEUROBORRELIOSIS AB Neurological manifestations of Lyme disease are usually accompanied by inflammatory changes in the cerebrospinal fluid (CSF) and the recruitment of activated T cells into the CSF compartment. In order to characterize the phenotype and identify target antigens of CSF-infiltrating T cells in early neuroborreliosis with central nervous system (CNS) involvement, we combined T-cell cloning, functional testing of T-cell responses with positional scanning synthetic combinatorial peptide libraries, and biometric data analysis. We demonstrate that CD4(+) gamma interferon-producing T cells specifically responding to Borrelia burgdorferi lysate were present in the CSF of a patient with acute Lyme encephalitis. Some T-cell clones recognized previously uncharacterized B. burgdorferi epitopes which show a specific enrichment for lysine, such as the heat shock-induced chaperone HSP90. Degenerate T-cell recognition that included T-cell responses to borrelia-specific and CNS-specific autoantigens derived from the myelin protein 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) could be demonstrated for one representative clone. Our results show that spirochetal antigen-specific and Th1-polarized CD4(+) lymphocytes infiltrate the CSF during monophasic CNS symptoms of Lyme disease and demonstrate that cross-recognition of CNS antigens by B. burgdorferi-specific T cells is not restricted to chronic and treatment-resistant manifestations. C1 Univ Clin Eppendorf, Ctr Mol Neurobiol Hamburg ZMNH, INiMS, Inst Neuroimmunol & Clin MS Res, D-20251 Hamburg, Germany. NINDS, Neuroimmunol Branch, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Mixture Sci & Torrey Pines Inst Mol Studies, San Diego, CA 92120 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Viral Immunobiol, New York, NY 10021 USA. Humboldt Univ, Charite, Med Ctr, Dept Neurol & Psychiat, D-10098 Berlin, Germany. RP Martin, R (reprint author), Univ Clin Eppendorf, Ctr Mol Neurobiol Hamburg ZMNH, INiMS, Inst Neuroimmunol & Clin MS Res, Falkenried 94, D-20251 Hamburg, Germany. EM roland.martin@zmnh.uni-hamburg.de RI Lunemann, Jan/G-8729-2011 OI Lunemann, Jan/0000-0002-3007-708X FU Intramural NIH HHS NR 54 TC 7 Z9 8 U1 1 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 JAN PY 2007 VL 75 IS 1 BP 243 EP 251 DI 10.1128/IAI.01110-06 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 122MG UT WOS:000243230500026 PM 17060473 ER PT J AU Coleman, SA Fischer, ER Cockrell, DC Voth, DE Howe, D Mead, DJ Samuel, JE Heinzen, RA AF Coleman, Sherry A. Fischer, Elizabeth R. Cockrell, Diane C. Voth, Daniel E. Howe, Dale Mead, David J. Samuel, James E. Heinzen, Robert A. TI Proteome and antigen profiling of Coxiella burnetii developmental forms SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; Q-FEVER; PHASE-I; EXPRESSION; STRESS; CYCLE; IDENTIFICATION; MORPHOGENESIS; TRANSCRIPTION; HOMOCYSTEINE AB A biphasic developmental cycle whereby highly resistant small-cell variants (SCVs) are generated from large-cell variants (LCVs) is considered fundamental to the virulence of Coxiella burnetti, the causative agent of human Q fever. In this study a proteome analysis of C. burnetii developmental forms was conducted to provide insight into their unique biological and immunological properties. Silver-stained gels of SCV and LCV lysates separated by two-dimensional (2-D) gel electrophoresis resolved over 675 proteins in both developmental forms. Forty-eight proteins were greater than twofold more abundant in LCVs than in SCVs, with six proteins greater than twofold more abundant in SCVs than in LCVs. Four and 15 upregulated proteins of SCVs and LCVs, respectively, were identified by mass spectrometry, and their predicted functional roles are consistent with a metabolically active LCV and a structurally resistant SCV. One-dimensional and 2-D immunoblots of cell form lysates probed with sera from infected/vaccinated guinea pigs and convalescent-phase serum from human patients who had recovered from acute Q fever, respectively, revealed both unique SCV/LCV antigens and common SCV/LCV antigens that were often differentially synthesized. Antigens recognized during human infection were identified by mass spectroscopy and included both previously described immunodominant proteins of C burnetii and novel immunogenic proteins that may be important in the pathophysiology of clinical Q fever and/or the induction of protective immunity. C1 NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Host Parasite Interact Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Microscopy Unit, Res Technol Sect, Res Technol Branch,Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. Texas A&M Univ Syst, Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. RP Heinzen, RA (reprint author), NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [U54 AI057156, AI057156] NR 42 TC 41 Z9 70 U1 1 U2 5 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 JAN PY 2007 VL 75 IS 1 BP 290 EP 298 DI 10.1128/IAI.00883-06 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 122MG UT WOS:000243230500031 PM 17088354 ER PT J AU Morinaga, N Yahiro, K Matsuura, G Watanabe, M Nomura, F Moss, J Noda, M AF Morinaga, Naoko Yahiro, Kinnosuke Matsuura, Gen Watanabe, Masaharu Nomura, Furnio Moss, Joel Noda, Masatoshi TI Two distinct cytotoxic activities of subtilase cytotoxin produced by shiga-toxigenic Escherichia coli SO INFECTION AND IMMUNITY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; EXTRACELLULAR SERINE-PROTEASE; VESICLE PROTON PUMP; HELICOBACTER-PYLORI; DIPHTHERIA-TOXIN; VACUOLATING TOXIN; BINDING; STRAINS; DOMAIN; TRANSLOCATION AB Subtilase cytotoxin (SubAB) is a recently identified AB5 subunit toxin produced by Shiga-toxigenic Escherichia coli. The A subunit is thought to be a subtilase-like, serine protease, whereas the B subunit binds to the toxin receptor on the cell surface. We cloned the genes from a clinical isolate; the toxin was produced as His-tagged proteins. SubAB induced vacuolation at concentrations greater than 1 mu g/ml after 8 h, in addition to the reported cytotoxicity induced at a ng/ml level after 48 h. Vacuolation was induced with the B, but not the A, subunit and was dependent on V-type ATPase. The cytotoxicity of SubAB at low concentrations was associated with the inhibition of protein synthesis; the 50% inhibitory dose was similar to 1 ng/ml. The A subunit, containing serine 272, which is thought to be a part of the catalytic triad of a subtilase-like serine protease, plus the B subunit was necessary for this activity, both in vivo and in vitro. SubAB did not cleave azocasein, bovine serum albumin, ovalbumin, or synthetic peptides. These data suggest that SubAB is a unique AB toxin: first, the B subunit alone can induce vacuolation; second, the A subunit containing serine 272 plus the B subunit inhibited protein synthesis, both in vivo and in vitro; and third, the A subunit proteolytic activity may have a strict range of substrate specificity. C1 Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, Chiba 2608670, Japan. Chiba Univ, Grad Sch Med, Dept Pediat Surg, Chuo Ku, Chiba 2608670, Japan. Chiba Univ, Grad Sch Med, Dept Mol Diag & Clin Genet, Chuo Ku, Chiba 2608670, Japan. Chiba Univ Hosp, Div Lab Med, Chuo Ku, Chiba 2608670, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Morinaga, N (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM nmorinaga@faculty.chiba-u.jp NR 38 TC 29 Z9 29 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 JAN PY 2007 VL 75 IS 1 BP 488 EP 496 DI 10.1128/IAI.01336-06 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 122MG UT WOS:000243230500052 PM 17101670 ER PT J AU Yan, Y Tan, Q Wang, Y Wang, DL Jin, M Gordon, T Lubet, RA You, M AF Yan, Ying Tan, Qing Wang, Yian Wang, Daolong Jin, Mike Gordon, Terry Lubet, Ronald A. You, Ming TI Enhanced lung tumor development in tobacco smoke-exposed p53 transgenic and Kras2 heterozygous deficient mice SO INHALATION TOXICOLOGY LA English DT Article; Proceedings Paper CT 10th International Inhalation Symposium CY MAY 31-JUN 03, 2006 CL Hannover, GERMANY SP German Soc Toxicol, Fraunhofer Inst Toxicol & Expt Med, Natl Hlth & Environm Effects Res Lab, US EPA ID MOUSE LUNG; K-RAS; CANCER; CHEMOPREVENTION; CARCINOGENESIS; TUMORIGENESIS AB A/J mice bearing either a mutation in the p53 gene or a Kras2 heterozygous deficiency were investigated for their susceptibility to tobacco smoke-induced lung tumorigenesis. Transgenic mice and their wild-type littermates were exposed to mainstream tobacco smoke (MS) for 5 mo, followed by 4 mo of recovery in filtered air. In sham (filtered air) groups, p53 transgenic mice did not exhibit a higher tumor multiplicity but did exhibit larger tumors, with tumor load increased 3.6-fold, when compared with wild-type mice. With exposure to MS, tumor multiplicity was increased 60% but there was a strikingly increased tumor load (15.9-fold) in p53 transgenic mice. Increased tumor load (5.3-fold) but not tumor multiplicity was seen in MS-exposed Kras2 heterozygous deficient mice. Interestingly, MS exposure did not increase benzo[a]pyrene-induced lung tumorigenesis when MS exposure was initiated after BaP treatment. These results indicate that a p53 mutation or loss of a Kras2 allele increases susceptibility to MS-induced lung tumor development. C1 Washington Univ, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. NYU, Sch Med, Dept Environm Med, Tuxedo Pk, NY USA. Natl Canc Inst, Chemoprevent Branch, Bethesda, MD USA. RP You, M (reprint author), Washington Univ, Dept Surg, Alvin J Siteman Canc Ctr, 660 S Euclid Ave,Campus Box 8109,10130 Wohl Clin, St Louis, MO 63110 USA. EM youm@wudosis.wustl.edu NR 22 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PY 2007 VL 19 SU 1 BP 183 EP 187 DI 10.1080/08958370701496160 PG 5 WC Toxicology SC Toxicology GA 210CM UT WOS:000249434300025 PM 17886066 ER PT J AU Doherty, SP Prophete, C Maciejczyk, P Salnikow, K Gould, T Larson, T Koenig, J Jaques, P Sioutas, C Zelikoff, JT Lippmann, M Cohen, MD AF Doherty, S. P. Prophete, C. Maciejczyk, P. Salnikow, K. Gould, T. Larson, T. Koenig, J. Jaques, P. Sioutas, C. Zelikoff, J. T. Lippmann, M. Cohen, M. D. TI Detection of changes in alveolar macrophage iron status induced by select PM2.5-associated components using iron-response protein binding activity SO INHALATION TOXICOLOGY LA English DT Article ID OXIDATIVE STRESS; NITRIC-OXIDE; REGULATORY PROTEIN-1; PARTICULATE MATTER; CELL-LINE; TRANSFERRIN; RAT; MANGANESE; METABOLISM; EXPOSURE AB The extent of adverse health effects, including induction/ exacerbation of infectious lung disease, arising from entrainment of equivalent amounts ( or exposure to a fixed increment) of fine particulate matter ( PM2.5) can vary from region to region or city to city in a region. To begin to explain how differing effects on host resistance might arise after exposure to PM2.5 from various sites, we hypothesized that select metals ( e. g., V, Al, and Mn) in each PM2.5 caused changes in alveolar macrophage ( AM) Fe status that, ultimately, would lead to altered antibacterial function. To test this, iron-response protein ( IRP) binding activity in a rat AM cell line was assessed after exposure to Fe alone and in conjunction with V, Mn, and/ or Al at ratios of V: Fe, Al: Fe, or Mn: Fe encountered in PM2.5 samples from New York City, Los Angeles, and Seattle. Results indicated that V and Al each significantly altered IRP activity, though effects were not consistently ratio- ( i. e., dose-) dependent; Mn had little impact on activity. We conclude that the reductions in Fe status detected here via the IRP assay arose, in part, from effects on transferrin- mediated Fe3+ delivery to the AM. Ongoing studies using this assay are allowing us to better determine: ( 1) whether mass ( and/ or molar) relationships between Fe and V, Al, and/ or Mn in any PM2.5 sample consistently govern the extent of change in AM Fe status; ( 2) how much any specified PM2.5 constituent ( metal or nonmetal) contributes to the overall disruption of Fe status found induced by an intact parent sample; and ( 3) whether induced changes in binding activity are relatable to other changes expected to occur in the AM, that is, in IRP- dependent mRNA/ levels of ferritin/ transferrin receptor and Fe- dependent functions. These studies demonstrate that pollutant- induced effects on lung cell Fe status can be assessed in a reproducible manner using an assay that can be readily performed by investigators who might otherwise have no access to other very costly analytical equipment, such as graphite atomic absorption or x- ray fluorescence spectro( photo) meters. C1 NYU, Sch Med, Nelson Inst Environm Med, NYU EPA Particulate Matter Hlth Res Ctr, Tuxedo Pk, NY 10987 USA. NCI, Frederick, MD 21701 USA. Univ Washington, NW Ctr Particulate Matter & Hlth, Seattle, WA 98195 USA. Clarkson Univ, Dept Biol, Ctr Air Resources Engn & Sci, Potsdam, NY 13699 USA. Univ So Calif, Los Angeles, CA USA. RP Cohen, MD (reprint author), NYU, Sch Med, Nelson Inst Environm Med, NYU EPA Particulate Matter Hlth Res Ctr, 57 Old Forge Rd, Tuxedo Pk, NY 10987 USA. EM cohenm@env.med.nyu.edu FU NIEHS NIH HHS [ES00260]; NIGMS NIH HHS [GM065458] NR 39 TC 5 Z9 5 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PY 2007 VL 19 IS 6-7 BP 553 EP 562 DI 10.1080/08958370701280481 PG 10 WC Toxicology SC Toxicology GA 171PP UT WOS:000246748200008 PM 17497533 ER PT J AU Bennett, WD Hazucha, MJ Folinsbee, LJ Bromberg, PA Kissling, GE London, SJ AF Bennett, William D. Hazucha, Milan J. Folinsbee, Lawrence J. Bromberg, Philip A. Kissling, Grace E. London, Stephanie J. TI Acute pulmonary function response to ozone in young adults as a function of body mass index SO INHALATION TOXICOLOGY LA English DT Article ID OBESE MICE; HUMAN-LUNG; AIRWAY; EXPOSURE; INFLAMMATION; DISEASE; HUMANS; GENDER; SYSTEM; MUSCLE AB Recent studies have shown enhanced responsiveness to ozone in obese mice. Adiposity has not been examined as a possible modulator of ozone response in humans. We therefore examined the relationship between body mass index and the acute spirometric response to ozone (O-3) exposure among 197 nonasthmatic young adults (aged 18-35 yr) studied in our human exposure facility from 1992 to 1998. Each subject had been exposed to 0.42 ppm O-3 for 1.5 h with intermittent exercise designed to produce a minute ventilation of 20 L/min/m(2) body surface area (BSA). Spirometry (pulmonary function) was measured pre- and immediately postexposure to determine acute ozone-induced changes. The decrement in forced expiratory volume in 1s (Delta FEV1) as percent of baseline was significantly correlated with BMI, r = - 0.16, p =.03, with a slightly stronger correlation in women (n = 75), r = - 0.22, p =.05, and no significant correlation in men. BMI had a greater range in women than in men in our study. In women greater ozone-induced decrements were seen in overweight (BMI> 25 kg/m(2)) than in normal weight (BMI 18.5 to 25 kg/m(2)), and in normal weight than in underweight (BMI < 18.5 kg/m(2)) for all spirometric variables considered (p trend =.022). Although our population studied was predominantly normal weight, we found that higher body mass index may be a modest risk factor for adverse pulmonary effects associated with ozone exposure, especially for women. C1 Univ N Carolina, Ctr Environm Med, Chapel Hill, NC 27599 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Human Studies Div, Chapel Hill, NC USA. NIH, NIEHS, Dept Hlth & Human Serv, Div Intramural Res, Res Triangle Pk, NC USA. RP Bennett, WD (reprint author), Univ N Carolina, Ctr Environm Med, CB 7310,104 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM William_Bennett@med.unc.edu OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES043012-09] NR 30 TC 32 Z9 33 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PY 2007 VL 19 IS 14 BP 1147 EP 1154 DI 10.1080/08958370701665475 PG 8 WC Toxicology SC Toxicology GA 235ND UT WOS:000251240200004 PM 17987466 ER PT J AU Young, HA Bream, JH AF Young, H. A. Bream, J. H. TI IFN-gamma: Recent advances in understanding regulation of expression, biological functions, and clinical applications SO INTERFERON: THE 50TH ANNIVERSARY SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID T-CELL DIFFERENTIATION; NF-KAPPA-B; CYTOKINE GENE-EXPRESSION; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; MESSENGER-RNA; CUTTING EDGE; NK CELLS; HISTONE ACETYLATION; NUCLEAR FACTOR AB Interferon-gamma (IFN-gamma) is a key immunoregulatory protein that plays a major role in the host innate and adaptive immune response. Also known as type II interferon, IFN-gamma is a single-copy gene whose expression is regulated at multiple levels by the host. Transcription control is regulated through epigenetic mechanisms as well as the accessibility of chromatin and the binding of activating and inhibitory proteins to promoter and enhancer elements. Post-transcriptional control is mediated through mRNA localization and mRNA stability while post-translational control occurs through the activation of protein kinase R by the 5' portion of the mRNA, protein folding within the endoplasmic reticulum and the possible interaction of the mRNA with microRNAs. The biological effects of IFN-gamma are widespread, as almost every cell type is altered upon interaction with this protein. Thus it has become very apparent that IFN-gamma is a multipotent cytokine whose regulation and effects are complex and essential to host survival. C1 [Young, H. A.] Natl Canc Inst, Ctr Canc Res, Expt Immunol Lab, Ft Detrick, MD 21702 USA. [Bream, J. H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Young, HA (reprint author), Natl Canc Inst, Ctr Canc Res, Expt Immunol Lab, Ft Detrick, MD 21702 USA. EM younghow@mail.nih.gov; breamj@jhsph.edu RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 93 TC 68 Z9 72 U1 2 U2 11 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2007 VL 316 BP 97 EP 117 PG 21 WC Immunology; Microbiology SC Immunology; Microbiology GA BHA98 UT WOS:000251960800006 PM 17969445 ER PT J AU Yamamoto, H Kashio, Y Shoji, H Shinonaga, R Yoshimura, T Nishi, N Nabe, T Nakamura, T Kohno, S Hirashima, M AF Yamamoto, Hitomi Kashio, Yumiko Shoji, Hiroki Shinonaga, Rika Yoshimura, Teizo Nishi, Nozomu Nabe, Takeshi Nakamura, Takanori Kohno, Shigekatsu Hirashima, Mitsuomi TI Involvement of galectin-9 in guinea pig allergic airway inflammation SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Workshop on Eosinophils in Allergy and Related Diseases CY JUN 24, 2006 CL Tokyo, JAPAN SP Novartis Pharma DE galectin-9; allergic inflammation; asthma; animal model; guinea pig ID EOSINOPHIL CHEMOTACTIC LYMPHOKINES; FUNCTIONAL-HETEROGENEITY; LINKER PEPTIDE; ASTHMA; CELLS; TIM-3; CHEMOATTRACTANT; RESPONSES; DISEASE; ECALECTIN/GALECTIN-9 AB Background: There is little information about the involvement of galectin-9 (Gal-9) in allergic inflammation. Thus, we investigated the role of Gal-9 in asthma model guinea pigs. Methods: Airway resistance (R-aw) was measured using a double-flow plethysmograph system. Gal-9 expression in the lung was assessed by Western blot and immunohistochemistry. Eosinophil chemotactic activity was evaluated in a chamber containing a polyvinylpyrolidone-free membrane. Cell apoptosis was analyzed on a flowcytometry with propidium iodide. Results: In cloning guinea pig Gal-9 we identified three isoforms that differ only in the length of their linker peptides, just as with human Gal-9. Guinea pig Gal-9 was found to be a chemoattractant for eosinophils and to promote induction of apoptosis in sensitized but not non-sensitized T lymphocytes. In allergic airway hypersensitivity model, a low level of Gal-9 expression was observed in the nonsensitized/nonchallenged group, but upregulation was detected at 7 h after challenge and sustained up to 24 h. Such upregulation correlated with elevation of eosinophil peroxidase activity but not with increased R-aw. Conclusions: The present results provide evidence that Gal-9 is not involved in airway hypersensitivity, but is partly involved in prolonged eosinophil accumulation in the lung. Copyright (C) 2007 S. Karger AG, Basel. C1 Kagawa Univ, Fac Med, Dept Immunol & Immunopathol, Miki, Kagawa 7610793, Japan. Kyoto Pharmaceut Univ, Dept Pharmacol, Kyoto 607, Japan. Kagawa Univ, Fac Med, Dept Endocrinol, Takamatsu, Kagawa 760, Japan. Galpharma Co Ltd, Kagawa, Japan. NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. RP Hirashima, M (reprint author), Kagawa Univ, Fac Med, Dept Immunol & Immunopathol, 17500-1 Ikenobe, Miki, Kagawa 7610793, Japan. EM mitsuomi@kms.ac.jp NR 41 TC 18 Z9 21 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2007 VL 143 SU 1 BP 95 EP 105 DI 10.1159/000101414 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 182TS UT WOS:000247527500018 PM 17541286 ER PT J AU Iwaki, S Jensen, BM Giffillan, AM AF Iwaki, Shoko Jensen, Bettina M. Giffillan, Alasdair M. TI NTAL/LAB/LAT2 SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE NTAL; LAB; LAT2; transmembrane adaptor protein; mast cells ID MAST-CELL ACTIVATION; SIGNALING PATHWAYS; NEGATIVE REGULATION; LINKER; LAT; KIT AB Non-T cell activation linker (NTAL)/linker for activation of B cells (LAB), now officially termed LAT2 (linker for activation of T cells 2) is a 25-30 kDa transmembrane adaptorprotein (TRAP) associated with glycolipid-enriched membrane fractions (GEMs; lipid rafts) in specific cell types of hematopoietic lineage. Tyrosine phosphorylation of NTAL/LAB/LAT2 is induced by Fc epsilon RI aggregation and Kit dimerization in mast cells, Fc gamma RI aggregation in monocytes, and BCR aggregation in B cells. NTAL/LAB/LAT2 is also expressed in resting NK cells but, unlike the related TRAP, LAT, not in resting T cells. As demonstrated in monocytes and B cells, phosphorylated NTAL/LAB/LAT2 recruits signaling molecules such as Grb2, Gab1 and c-Cbl into receptor-signaling complexes. Although gene knock out and knock down studies have indicated that NTAL/LAB/LAT2 may function as both a positive and negative regulator of mast cell activation, its precise role in the activation of these and other hematopoietic cells remains enigmatic. Published by Elsevier Ltd. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Giffillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 16 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 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PY 2007 VL 39 IS 5 BP 868 EP 873 DI 10.1016/j.biocel.2006.10.018 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168PG UT WOS:000246535900004 PM 17118694 ER PT J AU McShane, L AF McShane, L. TI Multigene signatures for breast cancer management: Pandora's box or a jewelry box? A statistician's point of view SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD JAN-MAR PY 2007 VL 22 IS 1 BP 59 EP 59 PG 1 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 170BW UT WOS:000246637300024 ER PT J AU Cao, L Li, W Kim, S Brodie, SG Deng, CX AF Cao, L. Li, W. Kim, S. Brodie, S. G. Deng, C-X. TI Senescence, aging, and malignant transformation in Brca1 exon 11 isoform-deficient cells and mice SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Meeting Abstract C1 NIDDK, Genet Dev & Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD JAN-MAR PY 2007 VL 22 IS 1 BP 66 EP 66 PG 1 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 170BW UT WOS:000246637300037 ER PT J AU Lee, SB Selby, HM Kramer-Mareki, G Byun, JS Capala, J AF Lee, S. B. Selby, H. M. Kramer-Mareki, G. Byun, J. S. Capala, J. TI A novel affibody-alexa fluor fluorescent probe to detect HER2 receptors for near infrared optical imaging SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Meeting Abstract C1 NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. IIT, Dept Biomed Engn, Chicago, IL 60616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD JAN-MAR PY 2007 VL 22 IS 1 BP 84 EP 84 PG 1 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 170BW UT WOS:000246637300064 ER PT J AU Shukla, V Coumoul, X Deng, CX AF Shukla, Vivek Coumoul, Xavier Deng, Chu-Xia TI RNAi-based conditional gene knockdown in mice using a U6 promoter driven vector SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE RNAi; shRNA; pol III vectors; transgenic mice; protocol ID SMALL-INTERFERING-RNA; MAMMALIAN-CELLS; IN-VIVO; TRANSGENIC MICE; EXPRESSION; SYSTEM; SUPPRESSION; SIRNAS AB RNA interference (RNAi) is a powerful tool widely used for studying gene function in a number of species. We have previously developed an approach that allows conditional expression of a polymerase III promoter based small hairpin RNA ( shRNA) in mice using the Cre-LoxP system. This approach uses a U6 promoter, which is inactive due to the presence of a ploxPneo cassette in the promoter; this promoter can be activated after excision of the neo gene in transgenic mice that express a Cre recombinase transgene. As a proof of principle, we have previously knocked down over 95% of Fgfr2 transcripts in mouse germlines, leading to embryonic lethality, while restricting the knockdown to the progress zone of the limb results in live animals with malformation of digits of both the forelimbs and hindlimbs. We now provide a detailed protocol, including a simplified single-step cloning procedure for vector construction. This method provides a fast yet efficient way to decipher gene functions in vivo in a tissue specific manner. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 38 TC 14 Z9 16 U1 0 U2 3 PU IVYSPRING INTERNATIONAL PUBLISHER PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2007 VL 3 IS 2 BP 91 EP 99 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 174ZD UT WOS:000246980600004 PM 17304337 ER PT J AU Li, WM Sandhoff, R Kono, M Zerfas, P Hoffmann, V Ding, BCH Proia, RL Deng, CX AF Li, Wenmei Sandhoff, Roger Kono, Mari Zerfas, Patricia Hoffmann, Vickie Ding, Bryan Char-Hoa Proia, Richard L. Deng, Chu-Xia TI Depletion of ceramides with very long chain fatty acids causes defective skin permeability barrier function, and neonatal lethality in ELOVL4 deficient mice SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE ELOVL4; lipid; epidermis; keratinocyte differentiation; stratum corneum ID MACULAR DYSTROPHY; PHOTORECEPTOR DEGENERATION; GENE; METABOLISM; EPIDERMIS; ORGANIZATION; EXPRESSION; DISORDERS; ROLES; MODEL AB Very long chain fatty acids (VLCFA), either free or as components of glycerolipids and sphingolipids, are present in many organs. Elongation of very long chain fatty acids-4 (ELOVL4) belongs to a family of 6 members of putative fatty acid elongases that are involved in the formation of VLCFA. Mutations in ELOVL4 were found to be responsible for an autosomal dominant form of Stargardt's- like macular dystrophy ( STGD3) in human. We have previously disrupted the mouse Elovl4 gene, and found that Elovl4(+/-) mice were developmentally normal, suggesting that haploinsufficiency of ELOVL4 is not a cause for the juvenile retinal degeneration in STGD3 patients. However, Elovl4(-/-) mice died within several hours of birth for unknown reason(s). To study functions of ELOVL4 further, we have explored the causes for the postnatal lethality in Elovl4(-/-) mice. Our data indicated that the mutant mice exhibited reduced thickness of the dermis, delayed differentiation of keratinocytes, and abnormal structure of the stratum corneum. We showed that all Elovl4(-/-) mice exhibited defective skin water permeability barrier function, leading to the early postnatal death. We further showed that the absence of ELOVL4 results in depletion in the epidermis of ceramides with- hydroxy very long chain fatty acids (>= C28) and accumulation of ceramides with non omega-hydroxy fatty acids of C26, implicating C26 fatty acids as possible substrates of ELOVL4. These data demonstrate that ELOVL4 is required for VLCFA synthesis that is essential for water permeability barrier function of skin. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. German Canc Res Ctr, D-6900 Heidelberg, Germany. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI Proia, Richard/A-7908-2012; deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 29 TC 79 Z9 79 U1 0 U2 4 PU IVYSPRING INTERNATIONAL PUBLISHER PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2007 VL 3 IS 2 BP 120 EP 128 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 174ZD UT WOS:000246980600008 PM 17311087 ER PT J AU Deng, CX AF Deng, Chuxia TI In celebration of Dr. Mario R. Capecchi's Nobel Prize SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Editorial Material ID CULTURED MAMMALIAN-CELLS; EMBRYONIC STEM-CELLS; HOMOLOGOUS RECOMBINATION; REPLACEMENT VECTORS; GENE; FREQUENCY; GENOME; LOCUS; INT-2; DNA C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDK, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 13 TC 1 Z9 1 U1 1 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2007 VL 3 IS 7 BP 417 EP 419 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 268VJ UT WOS:000253607600003 PM 17998949 ER PT J AU Boonsathorn, W AF Boonsathorn, Wasita TI Understanding conflict management styles of Thais and Americans in multinational corporations in Thailand SO INTERNATIONAL JOURNAL OF CONFLICT MANAGEMENT LA English DT Article DE conflict management; Thailand; multinational companies; conflict; gender ID INDIVIDUALISM COLLECTIVISM; ORGANIZATIONAL CONFLICT; INTERPERSONAL CONFLICT; MANAGING-CONFLICT; UNITED-STATES; WORK TEAMS; GENDER; COMPETENCE; RESOLUTION; SELF AB Purpose - The purpose of this paper is to examine the preferences for conflict management styles of Thais and Americans in multinational corporations in Thailand. Gender and the length of exposure to other cultures were also taken into account as influences on the preference for conflict management styles. Design/methodology/approach - Quantitative methodology was used. A total of 250 Thais and 64 Americans from 73 multinational companies were asked to complete the questionnaires consisting of conflict management style instrument and a set of demographic information. ANOVAs and Pearson's correlations were used for data analysis. Findings - Thais, compared with Americans, preferred avoiding and obliging conflict management styles and exhibited no differences in preferences for other styles. Males and females did not exhibit differences in preferences for conflict management styles. There was a negative correlation between length of stay abroad for Thais and preference for avoiding and obliging conflict management styles, and a positive correlation between length of stay abroad for Thais and preference for a dominating conflict management style. Research limitations/implications - The language of the instrument, the small number of American female participants, and the positions of the participants may limit the generalization of the findings. Practical implications - The paper presents a very useful source of information for people working in multinational corporations and trainers in the area of intercultural communication. Originality/value - This paper provides new insight into the preference of conflict management styles in a multinational context, the entity in which people from many cultures directly interact (intercultural perspective). The length of exposure to other cultures was also investigated in relation to the preference of conflict management styles. C1 [Boonsathorn, Wasita] NIDA, Sch Human Resource Dev, Bangkok, Thailand. RP Boonsathorn, W (reprint author), NIDA, Sch Human Resource Dev, Bangkok, Thailand. EM wasita@nida.nida.ac.th NR 63 TC 11 Z9 11 U1 2 U2 11 PU EMERALD GROUP PUBLISHING LIMITED PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 1044-4068 J9 INT J CONFL MANAGE JI Int. J. Confl. Manage. PY 2007 VL 18 IS 3-4 BP 196 EP 221 DI 10.1108/10444060710825972 PG 26 WC Communication; Management; Political Science SC Communication; Business & Economics; Government & Law GA 240XJ UT WOS:000251621200001 ER PT J AU Zhao, H Rebbert, ML Dawid, IB AF Zhao, Hui Rebbert, Martha L. Dawid, Igor B. TI Myoskeletin, a factor related to Myocardin, is expressed in somites and required for hypaxial muscle formation in Xenopus SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE myocardin; skeletal muscle; hypaxial muscle; somite ID MESODERM-INDUCING FACTOR; CARDIAC GENE-EXPRESSION; SERUM RESPONSE FACTOR; SKELETAL-MUSCLE; TRANSCRIPTIONAL COACTIVATORS; VERTEBRATE EMBRYOS; ACTIVIN-A; DIFFERENTIATION; MYOGENESIS; FAMILY AB Myoskeletin was identified as a gene induced by activin in animal cap explants of Xenopus laevis. This gene encodes a protein related to the transcription factor Myocardin. Whereas Myocardin is expressed in the heart and is known to be involved in heart and smooth muscle formation, Myoskeletin is expressed in the somites and in hypaxial muscle precursors as they migrate away from the somites during tadpole stages. Myoskeletin is required for hypaxial muscle formation, as reduction of its expression through injection of an antisense morpholino oligonucleotide leads to suppression of hypaxial muscle formation. In overexpression experiments in animal caps, Myoskeletin is capable of inducing multiple genes including skeletal muscle, cardiac muscle and smooth muscle-specific genes. We conclude that Myoskeletin is a somite and hypaxial muscle-specific member of the Myocardin family that is required for hypaxial muscle formation. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Genet Mol Lab, NIH, Bldg 6B,Room 413, Bethesda, MD 20892 USA. EM idawid@nih.gov RI Zhao, Hui/B-8429-2016 FU Intramural NIH HHS NR 29 TC 1 Z9 1 U1 0 U2 3 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. PY 2007 VL 51 IS 4 BP 315 EP 320 DI 10.1387/ijdb.062260hz PG 6 WC Developmental Biology SC Developmental Biology GA 180UP UT WOS:000247391900006 PM 17554683 ER PT J AU Cretekos, CJ Deng, JM Green, ED Rasweiler, JJ Behringer, RR AF Cretekos, Chris J. Deng, Jian-Min Green, Eric D. Rasweiler, John J. Behringer, Richard R. CA NISC Comparat Sequencing Program TI Isolation, genomic structure and developmental expression of Fgf8 in the short-tailed fruit bat Carollia perspicillata SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE chiroptera; Carollia perspicillata; Fgf8; genomic structure; gene expression ID LIMB DEVELOPMENT; CARCINOMA-CELLS; EARLY MESODERM; MOUSE; GROWTH; RECEPTORS; EMBRYO; INACTIVATION; MAINTENANCE; INDUCTION AB Fibroblast growth factor-8 (Fgf8) encodes a secreted protein which was initially identified as the factor responsible for androgen-dependant growth of mouse mammary carcinoma cells (Tanaka et al., 1992). Fgf8 has been subsequently implicated in the patterning and growth of the gastrulating embryo, paraxial mesoderm (somites), limbs, craniofacial tissues, central nervous system and other organ systems during the development of several vertebrate model animals. Consistent with these findings, Fgf8 is expressed in a complex and dynamic pattern during vertebrate embryogenesis. Here we report the isolation and characterization of a bat (Carollia perspicillata) Fgf8 orthologue. Compared with those of other model vertebrates, Carollia FgfB is conserved with respect to genomic structure, sequence and many domains of developmental expression pattern. Interestingly, the expression domain marking the apical ectodermal ridge of the developing limb shows a striking difference compared to that of mouse, consistent with evolutionary diversification of bat limb morphology. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. NHGRI, NISC Comparat Sequencing Program, Genome Technol Branch, Bethesda, MD 20892 USA. NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. Suny Downstate Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. RP Behringer, RR (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM rrb@mdanderson.org RI Cretekos, Chris/D-8350-2013 FU Intramural NIH HHS; NCI NIH HHS [CA09299]; NICHD NIH HHS [HD97325] NR 37 TC 25 Z9 27 U1 0 U2 3 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. PY 2007 VL 51 IS 4 BP 333 EP 338 DI 10.1387/ijdb.062257cc PG 6 WC Developmental Biology SC Developmental Biology GA 180UP UT WOS:000247391900009 PM 17554686 ER PT J AU Bok, JW Chang, WS Wu, DK AF Bok, Jinwoong Chang, Weise Wu, Doris K. TI Patterning and morphogenesis of the vertebrate inner ear SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE inner ear; morphogenesis; vertebrate; axial specification; patterning ID SENSORY ORGAN GENERATION; PLANAR CELL POLARITY; CRANIAL NEURAL CREST; SONIC HEDGEHOG; HOMEOBOX GENE; MUTANT MICE; VESTIBULAR MORPHOGENESIS; DEVELOPMENTAL DEFECTS; TARGETED DISRUPTION; AXIAL SPECIFICATION AB The positional cues for formation of individual inner ear components are dependent on pre-established axial information conferred by inductive signals from tissues surrounding the developing inner ear. This review summarizes some of the known molecular pathways involved in establishing the three axes of the inner ear, anterior-posterior (AP), dorsal-ventral (DV) and medial-lateral (ML). Signals required to establish the AP axis of the inner ear are not known, but they do not appear to be derived from the hindbrain. In contrast, the hindbrain is essential for establishing the DV axis of the inner ear by providing inductive signals such as Wnts and Sonic hedgehog. Signaling from the hindbrain is also required for the formation of the ML axis, whereas formation of the lateral wall of the otocyst may be a result of first establishing both the AP and DV axes. In addition, this review addresses how genes induced within the otic epithelium as a result of axial specification continue to mediate inner ear morphogenesis. C1 NIDCD, Rockville, MD 20850 USA. RP Wu, DK (reprint author), NIDCD, 5 Res Ct,Rm 2b34, Rockville, MD 20850 USA. EM wud@nidcd.nih.gov RI Bok, Jinwoong/B-8982-2016 OI Bok, Jinwoong/0000-0003-1958-1872 FU Intramural NIH HHS NR 96 TC 70 Z9 73 U1 0 U2 6 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. PY 2007 VL 51 IS 6-7 BP 521 EP 533 DI 10.1387/ijdb.072381jb PG 13 WC Developmental Biology SC Developmental Biology GA 239MW UT WOS:000251523400010 PM 17891714 ER PT J AU Kelley, MW AF Kelley, Matthew W. TI Cellular commitment and differentiation in the organ of Corti SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Review DE hair cell; ear; otocyst; atch1; notch ID MAMMALIAN INNER-EAR; FIBROBLAST-GROWTH-FACTOR; LOOP-HELIX PROTEINS; AUDITORY SENSORY EPITHELIUM; UNIQUE EXPRESSION PATTERN; DEVELOPING NERVOUS-SYSTEM; NOTCH SIGNALING PATHWAY; OTIC PLACODE INDUCTION; COCHLEAR HAIR-CELLS; LUNATIC-FRINGE AB The organ of Corti, the sensory epithelium of the mammalian cochlea, develops from a subset of cells located along the dorsal side (referred to as the floor) of the cochlear duct. Over the course of embryonic development, cells within the developing organ of Corti become committed to develop as each of the unique cell types within the organ, including inner and outer hair cells, and at least four different types of supporting cells. Moreover, these different cell types are subsequently arranged into a highly rigorous cellular mosaic that includes the formation of ordered rows of both hair cells and supporting cells. The events that regulate both the location of the organ of Corti within the cochlear duct, the specification of each cell type and cellular patterning remain poorly understood. However, recent results have significantly improved our understanding of the molecular, genetic and cellular factors that mediate some of the decisions required for the development of this structure. In this review I will present an overview of cochlear development and then discuss some of the most recent and enlightening results regarding the molecular mechanism underlying the formation of this remarkable structure. C1 Natl Inst Hlth, Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, Bethesda, MD USA. RP Kelley, MW (reprint author), 35 Convent Dr, Bethesda, MD 20892 USA. EM kelleymt@nidcd.nih.gov FU Intramural NIH HHS NR 115 TC 49 Z9 53 U1 0 U2 7 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. PY 2007 VL 51 IS 6-7 BP 571 EP 583 DI 10.1387/ijdb.072388mk PG 13 WC Developmental Biology SC Developmental Biology GA 239MW UT WOS:000251523400014 PM 17891718 ER PT J AU Swamynathan, SK Piatigorsky, J AF Swamynathan, Shivalingappa K. Piatigorsky, Joram TI Regulation of the mouse alpha B-crystallin and MKBP/HspB2 promoter activities by shared and gene specific intergenic elements: the importance of context dependency SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE crystallin; gene regulation; promoter activity; enhancer; development ID HEAT-SHOCK-PROTEIN; LENS EPITHELIAL-CELLS; LONG TERMINAL REPEAT; RANGE INTRACHROMOSOMAL INTERACTIONS; IMMUNODEFICIENCY-VIRUS TYPE-1; ENHANCER-BLOCKING ACTIVITY; BETA-GLOBIN INSULATOR; E-BOX MOTIF; TRANSCRIPTIONAL REGULATION; TRANSGENIC MICE AB The closely linked (863 bp), divergently arranged mouse myotonic dystrophy kinase binding protein (Mkbp)/HspB2 and small heat shock protein (shsp)alpha B-crystallin genes have different patterns of tissue-specific expression. We showed previously that an intergenic enhancing region (-436/-257 relative to aB-crystallin transcription start site) selectively activates the alpha B-crystallin promoter in an orientation-dependent manner (Swamynathan, S.K. and J. Piatigorsky 2002. J. Biol. Chem. 277:49700-6). Here we show that cis-elements alpha BE1 (420096) and alpha BE3 (-320/-300) functionally interact with glucocorticoid receptor (GR) and Sp1, respectively, both in vitro and in vivo. alpha BE1:GR regulates both the HspB2 and alpha B-crystallin promoters, while alpha BE3:Sp1 selectively regulates the alpha B-crystallin promoter, as judged by mutagenesis and co-transfection tests. Enhancer blocking assays indicate that the -836/-622 fragment can act as a negative regulator in transfection tests, raising the possibility that it contributes to the differential expression of the proximal HspB2 promoter and distal alpha B-crystallin promoter. Finally, experiments utilizing transiently transfected cells and transgenic mice show that two conserved E-box elements (-726/-721 and -702/-697) bind nuclear proteins and differentially regulate the HspB2 and alpha B-crystallin promoters in a tissue-specific manner. Taken together, our results indicate that the linked, differentially expressed HspB2 and alpha B-crystallin genes have evolved shared and promoter-preferred cis-control elements within the intergenic sequence. The context-dependency of cis-elements provides multiple opportunities for evolutionary novelty by small sequence changes. 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,Room 101, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov OI Swamynathan, Shivalingappa/0000-0002-9158-1511 FU Intramural NIH HHS NR 72 TC 10 Z9 10 U1 0 U2 0 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. PY 2007 VL 51 IS 8 BP 689 EP 700 DI 10.1387/ijdb.072302ss PG 12 WC Developmental Biology SC Developmental Biology GA 234WF UT WOS:000251194200001 PM 17939115 ER PT J AU Rivera-Rentas, A Vilches, M Davila, E Rebollo, C Rodriguez, M Garcia, J Seguinot, S AF Rivera-Rentas, A. Vilches, M. Davila, E. Rebollo, C. Rodriguez, M. Garcia, J. Seguinot, S. TI Environmental awareness through integration of research and education: a case study from two elementary public schools in Puerto Rico SO INTERNATIONAL JOURNAL OF ENVIRONMENT AND POLLUTION LA English DT Article DE environmental education; constructivism; environmental research; K12 science education; community participation AB This work integrated environmental education, science, technology and research in a fifth grade science curriculum in two elementary public suburban schools in Carolina, Puerto Rico. Results are presented of these collaborative teams between a graduate fellow and a fifth grade science teacher. The teams developed educational and scientific strategies using a constructivism approach that promoted cooperative learning, students' active participation and the integration of the school community. A month-long lesson on waste management and water resources was developed based on students' research on community environmental perceptions. Students' academic achievement in science was significantly improved by the implemented strategies, seen as a 50% increase in the number of excellent (A) and good (B) grades. Through this work, the students completed scientific research projects of environmental significance for their communities and presented them at the school's science fair and environmental day. The implementation of constructivism strategies along the integration of technology, and hands-on and minds-on activities promoted students' interest in environment and science. C1 [Rivera-Rentas, A.] NIGMS, NIH, Bethesda, MD 20892 USA. [Vilches, M.; Davila, E.; Rebollo, C.; Rodriguez, M.; Garcia, J.; Seguinot, S.] Univ Metropolitana, Dept Biol, Sch Sci & Technol, Gurabo, PR 00778 USA. RP Rivera-Rentas, A (reprint author), NIGMS, NIH, Bethesda, MD 20892 USA. EM riverara@nigms.nih.gov NR 8 TC 1 Z9 1 U1 2 U2 11 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVA, SWITZERLAND SN 0957-4352 J9 INT J ENVIRON POLLUT JI Int. J. Environ. Pollut. PY 2007 VL 31 IS 3-4 BP 359 EP 370 PG 12 WC Environmental Sciences SC Environmental Sciences & Ecology GA 268DO UT WOS:000253558800010 ER PT J AU Reid, BC Psoter, WJ Gebrian, B Wang, MQ AF Reid, Britt C. Psoter, Walter J. Gebrian, Bette Wang, Min Qi TI The effect of an international embargo on malnutrition and childhood mortality in rural Haiti SO INTERNATIONAL JOURNAL OF HEALTH SERVICES LA English DT Article ID ECONOMIC SANCTIONS; GROWTH REFERENCE; HUMAN-RIGHTS; US EMBARGO; HEALTH; CRISIS; IMPACT; CUBA AB The study objective was to determine the effect of an international embargo against Haiti, from October 1991 through October 1994, on early childhood protein-energy malnutrition and all-cause mortality in a geographic area where humanitarian aid was continuously available to the children in the study. The authors used longitudinal anthropometric records on 1,593 children, 24 months old or younger, living in the rural Grand Anse Department of Haiti from 1989 through 1996. Kaplan-Meier graphs for all-cause mortality accounting for malnutrition status and stratified by calendar period were applied to the database and assessed using logrank tests. Adjusted relative risks were assessed by Cox regression. The results show that despite the continuous availability of preventive services (1989-1996), higher all-cause mortality was more strongly associated with a calendar period coinciding with the international embargo than with periods before and after the embargo. The incidence of childhood mortality and of severe malnutrition were also higher during the period of the embargo than in the periods before and after the embargo. The findings suggest that future international sanctions, even those with humanitarian/medical exceptions, could result in substantial infant death. C1 NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Reid, BC (reprint author), NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 5104,6130 Execut Blvd,MSC 732, Bethesda, MD 20892 USA. EM reidbr@mail.nih.gov FU NIDCR NIH HHS [5 R01 DE014708-03] NR 20 TC 2 Z9 2 U1 1 U2 7 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0020-7314 J9 INT J HEALTH SERV JI Int. J. Health Serv. PY 2007 VL 37 IS 3 BP 501 EP 513 DI 10.2190/MR65-2605-1285-0406 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 202LK UT WOS:000248902900006 PM 17844931 ER PT J AU Hu, ZZ Valencia, JC Huang, HZ Chi, A Shabanowitz, J Hearing, VJ Appella, E Wu, C AF Hu, Zhang-Zhi Valencia, Julio C. Huang, Hongzhan Chi, An Shabanowitz, Jeffrey Hearing, Vincent J. Appella, Ettore Wu, Cathy TI Comparative bioinformatics analyses and profiling of lysosome-related organelle proteomes SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE lysosome-related organelle (LRO); organelle proteome; proteomics; bioinformatics; protein database ID HEART MITOCHONDRIAL PROTEOME; MASS-SPECTROMETRY; SUBCELLULAR PROTEOMICS; GRISCELLI-SYNDROME; TARGETING SIGNALS; SMALL GTPASE; CELLS; ENDOCYTOSIS; TRAFFICKING; LOCALIZATION AB Complete and accurate profiling of cellular organelle proteomes, while challenging, is important for the understanding of detailed cellular processes at the organelle level. Mass spectrometry technologies coupled with bioinformatics analysis provide an effective approach for protein identification and functional interpretation of organelle proteomes. In this study, we have compiled human organelle reference datasets from large-scale proteomic studies and protein databases for seven lysosome-related organelles (LROs), as well as the endoplasmic reticulum and mitochondria, for comparative organelle proteome analysis. Heterogeneous sources of human organelle proteins and rodent homologs are mapped to human UniProtKB protein entries based on ID and/or peptide mappings, followed by functional annotation and categorization using the iProXpress proteomic expression analysis system. Cataloging organelle proteomes allows close examination of both shared and unique proteins among various LROs and reveals their functional relevance. The proteomic comparisons show that LROs are a closely related family of organelles. The shared proteins indicate the dynamic and hybrid nature of LROs, while the unique transmembrane proteins may represent additional candidate marker proteins for LROs. This comparative analysis, therefore, provides a basis for hypothesis formulation and experimental validation of organelle proteins and their functional roles. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Cellular Biol, Washington, DC 20007 USA. Univ Virginia, Dept Chem, Charlottesville, VA USA. RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2140, Bethesda, MD 20892 USA. EM appellae@nih.gov; wuc@georgetown.edu RI Crozier, Laura/A-4821-2010 FU NHGRI NIH HHS [U01 HG002712, U01 HG002712-03, U01 HG002712-03S1]; NIAID NIH HHS [HHSN266200400061C]; NIGMS NIH HHS [R01 GM037537]; PHS HHS [HHSN266200400061C] NR 65 TC 33 Z9 36 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD JAN 1 PY 2007 VL 259 IS 1-3 BP 147 EP 160 DI 10.1016/j.ijms.2006.09.024 PG 14 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 121TQ UT WOS:000243180300020 PM 17375895 ER PT J AU Chi, A Bai, DL Geer, LY Shabanowitz, J Hunt, DF AF Chi, An Bai, Dina L. Geer, Lewis Y. Shabanowitz, Jeffrey Hunt, Donald F. TI Analysis of intact proteins on a chromatographic time scale by electron transfer dissociation tandem mass spectrometry SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE ETD; PTR ID ESCHERICHIA-COLI; SEQUENCE-ANALYSIS; ION/ION REACTIONS; PEPTIDE; IDENTIFICATION; RIBOSOME; ACID AB Direct analysis of intact proteins on a chromatographic time scale is demonstrated on a modified linear ion trap mass spectrometer using sequential ion/ion reactions, electron transfer and proton transfer, to dissociate the sample and to convert the resulting peptide fragments to a mixture of singly and doubly charged species. Proteins are converted to gas-phase, multiply charged, positive ions by electrospray ionization and then allowed to react with fluoranthene radical anions. Electron transfer to the multiply charged protein promotes random fragmentation of amide bonds along the protein backbone. Multiply charged fragment ions are then deprotonated in a second ion/ion reaction with even-electron benzoate anions. m/z values for the resulting singly and doubly charged ions are used to read a sequence of 15-40 amino acids at both the N-terminus and the C-terminus of the protein. This information, along with the measured mass of the intact protein, are employed to identify known proteins and to detect the presence of post-translational modifications. In this study, we analyze intact proteins from the Escherchia coli 70S ribosomal protein complex and identify 46 of the 55 known unique components in a single, 90 min, on-line, chromatography experiment. Truncated versions of the above proteins along with several post-translational modifications are also detected. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Virginia, Dept Pathol, Hlth Sci Ctr, Charlottesville, VA 22908 USA. RP Shabanowitz, J (reprint author), Univ Virginia, Dept Chem, Mccormick Rd, Charlottesville, VA 22904 USA. EM js4c@virginia.edu RI Hunt, Donald/I-6936-2012; Geer, Lewis/H-2714-2014 OI Hunt, Donald/0000-0003-2815-6368; FU NIGMS NIH HHS [R01 GM037537, R01 GM037537-20] NR 17 TC 64 Z9 65 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD JAN 1 PY 2007 VL 259 IS 1-3 BP 197 EP 203 DI 10.1016/j.ijms.2006.09.030 PG 7 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 121TQ UT WOS:000243180300024 PM 17364019 ER PT J AU Roseti, L Facchini, A De Franceschi, L Marconi, E Major, EO Grigolo, B AF Roseti, Livia Facchini, Andrea De Franceschi, Luciana Marconi, Emanuele Major, Eugene O. Grigolo, Brunella TI Induction of original phenotype of human immortalized chondrocytes: A quantitative gene expression analysis SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE immortalized chondrocytes; serum-free culture; hyaluronan-based scaffold ID HUMAN ARTICULAR CHONDROCYTES; DIFFERENTIAL EXPRESSION; CELL-CULTURE; CATHEPSIN-B; CARTILAGE; GROWTH; TRANSPLANTATION; HYALURONAN; INVITRO; SOX9 AB We previously established a line of immortalized normal human articular chondrocytes, lbpva55, expressing the E6 and E7 transforming genes of the human papilloma virus type 16. With this study we investigated the phenotypic modulation ability of this cell line, cultured in different conditions, with the aim of validating its use for studies on cartilage metabolism and physiology. To this end, we performed a quantitative analysis, using real-time PCR technology, of the expression of the main structural components of the cartilage matrix (collagens 1, 11 and aggrecan), of two transcription factors regulating chondrocyte differentiation (Sox-9 and Egr-1) and of some enzymes involved in matrix turnover (cathepsin B, MMP-1 and MMP-13). Results showed that, under defined conditions, lbpva55 cells were able to re-express the chondrocyte phenotype that was lost in a conventional monolayer condition, as demonstrated by an up-regulation of collagen 11, the main marker of hyaline cartilage and Sox-9, a master gene regulator of chondrocytic differ-entiation. The gene expression profile of our immortalized cells compared with that of normal articular chondrocytes showed that this line could be used as a valid in vitro model for a better understanding of cell molecular mechanisms relevant for the development of new therapeutic approaches in rheumatic diseases and for the cartilage engineering field. C1 Ist Ric Codivilla PUtti, Ist Ortoped Rizzoli, Lab Immunol & Genet, I-40136 Bologna, Italy. Univ Bologna, Dipartimento Med INterna & Gastroenterol, I-40138 Bologna, Italy. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Grigolo, B (reprint author), Ist Ric Codivilla PUtti, Ist Ortoped Rizzoli, Lab Immunol & Genet, Via Barbiano 1-10, I-40136 Bologna, Italy. EM grigolob@alma.unibo.it RI Grigolo, Brunella/J-5417-2016 OI Grigolo, Brunella/0000-0002-3990-6745 NR 49 TC 3 Z9 3 U1 3 U2 5 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JAN PY 2007 VL 19 IS 1 BP 89 EP 96 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 121GZ UT WOS:000243147400012 PM 17143552 ER PT J AU Xie, JW Shen, ZM Li, KCP Danthi, N AF Xie, Jianwu Shen, Zhimin Li, King C. P. Danthi, Narasimhan TI Tumor angiogenic endothelial cell targeting by a novel integrin-targeted nanoparticle SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE targeted nanoparticle; integrin alpha(v)beta(3) cancer; angiogenesis ID IN-VIVO; ANTAGONIST AB Angiogenesis is an important process in cancer growth and metastasis. During the tumor angiogenic process, endothelial cells express various cell surface receptors which can be utilized for molecular imaging and targeted drug delivery. One such protein receptor of interest is the integrin alpha(v)beta(3) Our group is involved in the development of molecular imaging probes and drug delivery systems targeting alpha(v)beta(3) Based on extensive lead optimization study with the integrin antagonist compounds, we have developed a new generation of integrin alpha beta(3) compound (IA) which has superior binding affinity to alpha(v)beta(3) Utilizing this IA as a targeting agent, we have developed a novel integrin-targeted nanoparticle (ITNP) system for targeted drug delivery and imaging of cancer angiogenesis. When multiple copies of the IA were conjugated onto the nanoparticle surface, strong and selective binding to the integrin alpha beta(3) was observed. These ITNPs also were rapidly taken up by cells that express alpha(v)beta 3. The ITNPs acccumulated in the angiogenic vessels, after systemic administration in a murine squamous cell carcinoma model. This novel intergrin targeted ITNP platform will likely have an application in targeted delivery of drugs and genes in vivo and can also be used for molecular imaging. C1 [Xie, Jianwu; Li, King C. P.; Danthi, Narasimhan] NIH, Mol Imaging Lab, Bethesda, MD 20892 USA. [Shen, Zhimin] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Li, King C. P.] Methodist Hosp, Dept Radiol, Houston, TX 77030 USA. RP Danthi, N (reprint author), Bldg 10 Room 1N306,10 Ctr Dr, Bethesda, MD USA. EM ndanthi@cc.nih.gov RI Danthi, Simhan/B-7639-2014 FU Intramural NIH HHS NR 15 TC 22 Z9 24 U1 1 U2 7 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9114 J9 INT J NANOMED JI Int. J. Nanomed. PY 2007 VL 2 IS 3 BP 479 EP 485 PG 7 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 247BK UT WOS:000252051900019 PM 18019845 ER PT J AU Jin, SH Kim, SY Park, KH Lee, KJ AF Jin, Seung-Hyun Kim, Soo Yong Park, Kyung Hee Lee, Kil-Jae TI Differences in eeg between gifted and average students: Neural complexity and functional cluster analysis SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE functional cluster analysis; gifted students; neural complexity; Rey-Osterrieth complex figure test ID VISUAL MENTAL-IMAGERY; PREFRONTAL CORTEX; WORKING-MEMORY; INTELLIGENCE; FIGURE; PARAMETERS; ATTENTION; DYNAMICS; SYSTEM AB The main aim of the present study was to assess the differences in EEG between gifted and average students. Another aim of the present study was to investigate which brain areas are related to a Rey-Osterrieth complex figure (ROCF) memorizing using a functional cluster (FC) analysis and how the complexity of cortical activities changes in both gifted and average students. The EEG was recorded from 16 electrodes in both 18 right-handed healthy gifted and age-matched average students before and during ROCF memorizing. FC was estimated to characterize the joint interactions among many brain regions and neural complexity. The study assessed the visuo-spatial memory abilities through examining EEG profiles using the measure of FC, and planning and executive function using recall score. The gifted students made a significantly high score compared to the average students during ROCF memorizing. Both groups showed very different FC patterns. ROCF memorizing is related to the visual mental process, thus simultaneous neuronal activities appears on the right central, temporal, occipital, and bilateral prefrontal regions. One of the notable characteristics of gifted students' FC map is the dominance of the right hemisphere compared with that of average students, and it is accordance with the characteristics of gifted brain. C1 NIH, NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. Korea Adv Inst Sci & Technol, Dept Phys, Taejon 305701, South Korea. Jeonju Dukil Middle Sch, Jeonju, South Korea. Korea Natl Univ Educ, Dept Sci Educ, Chungbuk, South Korea. RP Jin, SH (reprint author), Korea Res Inst Stands & Sci, Human Life Measurement Grp, Taejon 305600, South Korea. EM shjin43@kaist.ac.kr RI Kim, Soo Yong/C-1944-2011 NR 41 TC 5 Z9 5 U1 2 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PY 2007 VL 117 IS 8 BP 1167 EP 1184 DI 10.1080/00207450600934655 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 193II UT WOS:000248267300005 PM 17613119 ER PT J AU Huff, J AF Huff, James TI Industry influence on occupational and environmental public health SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Editorial Material DE industry influence; government policy; worker health; science and politics; science manipulation ID INDUCED HEPATOCYTE PROLIFERATION; IARC MONOGRAPHS PROGRAM; CONFLICTS-OF-INTEREST; BUTYL-ETHER MTBE; SCIENTIFIC EVIDENCE; RISK-ASSESSMENT; UNITED-STATES; DI(2-ETHYLHEXYL)PHTHALATE DEHP; INTERNATIONAL-ORGANIZATIONS; DR. BRUNDTLAND,GRO,HARLEM AB Traditional covert influence of industry on occupational and environmental health (OEH) policies has turned brazenly overt in the last several years. More than ever before the OEH community is witnessing the perverse influence and increasing control by industry interests. Government has failed to support independent, public health-oriented practitioners and their organizations, instead joining many corporate endeavors to discourage efforts to protect the health of workers and the community. Scientists and clinicians must unite scientifically, politically, and practically for the betterment of public health and common good. Working together is the only way public health professionals can withstand the power and pressure of industry. Until public health is removed from politics and the influence of corporate money, real progress will be difficult to achieve and past achievements will be lost. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM huff1@niehs.nih.gov NR 196 TC 20 Z9 21 U1 1 U2 7 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1077-3525 EI 2049-3967 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JAN-MAR PY 2007 VL 13 IS 1 BP 107 EP 117 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 150CS UT WOS:000245193800016 PM 17427355 ER PT J AU Block, B Lin, CJ Heron, DE Neal-Ferguson, DL Bray, LA Goode, T Woods, MS AF Block, B. Lin, C. J. Heron, D. E. Neal-Ferguson, D. L. Bray, L. A. Goode, T. Woods, M. S. TI Cancer Outreach and education in African-American communities: A pre-post evaluation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Block, B.] Univ Pittsburgh, Med Ctr, Shadyside Priamry Care Inst, Pittsburgh, PA USA. [Lin, C. J.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Heron, D. E.] Univ Pittsburgh, Inst Canc, Shadyside Hosp, Dept Radiat Oncol, Pittsburgh, PA USA. [Neal-Ferguson, D. L.; Goode, T.; Woods, M. S.] Ctr Hlth Hearts & Souls, Pittsburgh, PA USA. [Bray, L. A.] NCI, Canc Informat Serv, Pittsburgh, PA 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S MA 2635 BP S556 EP S557 DI 10.1016/j.ijrobp.2007.07.1815 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950201321 ER PT J AU Li, G Guion, P Ning, H Citrin, D Xie, H Capala, J Arora, BC Camphausen, K Singh, AK Miller, RW AF Li, G. Guion, P. Ning, H. Citrin, D. Xie, H. Capala, J. Arora, B. C. Camphausen, K. Singh, A. K. Miller, R. W. TI A pancreas motion study using automatic image segmentation of time-resolved, single-slice MR images SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Li, G.; Guion, P.; Ning, H.; Citrin, D.; Xie, H.; Capala, J.; Arora, B. C.; Camphausen, K.; Singh, A. K.; Miller, R. W.] Natl Canc Inst, NIH, Radiat Oncol Branch, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S MA 2955 BP S736 EP S737 DI 10.1016/j.ijrobp.2007.07.2289 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950201638 ER PT J AU Mansueti, J Likhacheva, A Albert, P Scuito, L Harold, N Rudy, S Colevas, D Morris, JC Van Waes, C Citrin, D AF Mansueti, J. Likhacheva, A. Albert, P. Scuito, L. Harold, N. Rudy, S. Colevas, D. Morris, J. C. Van Waes, C. Citrin, D. TI Long term followup of a phase I study of concurrent paclitaxel and radiation for locally advanced squamous cell carcinoma of the head and neck SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Mansueti, J.; Likhacheva, A.; Albert, P.; Scuito, L.; Harold, N.; Rudy, S.; Morris, J. C.; Citrin, D.] Natl Canc Inst, Bethesda, MD USA. [Mansueti, J.] Natl Naval Med Ctr, Bethesda, MD USA. [Albert, P.; Van Waes, C.] NIH, Bethesda, MD 20892 USA. [Colevas, D.] Stanford Univ, Med Ctr, Stanford, CA 94305 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S BP S444 EP S444 DI 10.1016/j.ijrobp.2007.07.1610 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950201123 ER PT J AU Miller, RW Ning, H Justus, B Huston, A Li, G Chang, J Capala, J Xie, H Citrin, D Camphausen, K AF Miller, R. W. Ning, H. Justus, B. Huston, A. Li, G. Chang, J. Capala, J. Xie, H. Citrin, D. Camphausen, K. TI Use of an optical fiber dosimeter to measure small field output factors in stereotactic radiosurgery SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Miller, R. W.; Ning, H.; Li, G.; Chang, J.; Capala, J.; Xie, H.; Citrin, D.; Camphausen, K.] Natl Canc Inst, Bethesda, MD USA. [Justus, B.; Huston, A.] Naval Res Lab, Washington, DC 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S BP S647 EP S648 DI 10.1016/j.ijrobp.2007.07.1990 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950201489 ER PT J AU Mishra, MV Bisht, K Bradbury, C Gius, D AF Mishra, M. V. Bisht, K. Bradbury, C. Gius, D. TI The epigenome as molecular target for multi-modality resistant tumor cells SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Mishra, M. V.; Bisht, K.; Bradbury, C.; Gius, D.] NCI, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S MA 2732 BP S606 EP S606 DI 10.1016/j.ijrobp.2007.07.1914 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950201418 ER PT J AU Perkins, SM Singh, AK Rader, JS Powell, MA Mutch, DG Grigsby, PW AF Perkins, S. M. Singh, A. K. Rader, J. S. Powell, M. A. Mutch, D. G. Grigsby, P. W. TI Prospective phase if trial of prophylactic para-aortic irradiation and concurrent chemotherapy in cervical cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Perkins, S. M.; Grigsby, P. W.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. [Singh, A. K.] Natl Canc Inst, Radiat Oncol Branch, Bethesda, MD USA. [Rader, J. S.; Powell, M. A.; Mutch, D. G.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S BP S395 EP S395 DI 10.1016/j.ijrobp.2007.07.1517 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950201032 ER PT J AU Simone, NL Soule, BP Mitchell, CCJB Gins, DR AF Simone, N. L. Soule, B. P. Mitchell, C. Council J. B. Gins, D. R. TI MicroRNA expression is altered by ionizing radiation: A novel potential therapeutic target SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Simone, N. L.; Soule, B. P.; Mitchell, C. Council J. B.; Gins, D. R.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S BP S64 EP S64 DI 10.1016/j.ijrobp.2007.07.118 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950200115 ER PT J AU Singh, AK Guion, P Sears-Crouse, N Ullman, K Smith, S Albert, PS Choyke, P Wood, B Ning, H AF Singh, A. K. Guion, P. Sears-Crouse, N. Ullman, K. Smith, S. Albert, P. S. Choyke, P. Wood, B. Ning, H. TI Whole prostate to 75.6 with concurrent IMRT boost to 95 gray for biopsy proven, MRI defined dominant intraprostatic lesions: Early results of a phase INCI study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Singh, A. K.; Guion, P.; Sears-Crouse, N.; Ullman, K.; Smith, S.; Albert, P. S.; Choyke, P.; Wood, B.; Ning, H.] NCI, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S BP S369 EP S370 DI 10.1016/j.ijrobp.2007.07.1471 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950200658 ER PT J AU Stall, B Citrin, D Seidel, G Quezado, M Wood, B Denobile, J Libutti, S Camphausen, K AF Stall, B. Citrin, D. Seidel, G. Quezado, M. Wood, B. Denobile, J. Libutti, S. Camphausen, K. TI Early results of a pilot study of intra-tumoral injection of TNFerade TM biologic concurrent with neoadjuvant chemoradiation therapy for the treatment of primary and recurrent rectal cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 28-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut & Oncol C1 [Stall, B.; Citrin, D.; Seidel, G.; Quezado, M.; Wood, B.; Denobile, J.; Libutti, S.; Camphausen, K.] NIH, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2007 VL 69 IS 3 SU S BP S303 EP S304 DI 10.1016/j.ijrobp.2007.07.1356 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 217LU UT WOS:000249950200545 ER PT J AU Merrick, J AF Merrick, Joav TI The pillow angel Ashley and her treatment. Growth attenuation in severe intellectual disability SO INTERNATIONAL JOURNAL ON DISABILITY AND HUMAN DEVELOPMENT LA English DT Editorial Material C1 Minist Social Affairs, Jerusalem, Israel. NICHHD, Bethesda, MD 20892 USA. RP Merrick, J (reprint author), Minist Social Affairs, Jerusalem, Israel. EM jmerrick@zahav.net.il NR 5 TC 1 Z9 1 U1 1 U2 6 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 1565-012X J9 INT J DISABIL HUM DE JI Int. J. Disabil. Hum. Dev. PD JAN-MAR PY 2007 VL 6 IS 1 BP 1 EP 2 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 274NK UT WOS:000254007800001 ER PT S AU Woodard, GE Sage, SO Rosado, JA AF Woodard, Geoffrey E. Sage, Stewart O. Rosado, Juan A. BE Jeon, KW TI Transient receptor potential channels and intracellular signaling SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 256 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review; Book Chapter DE TRP; calcium signaling; cation channels; calcium entry; cell physiology ID CAPACITATIVE CALCIUM-ENTRY; OPERATED CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; NONSELECTIVE CATION CHANNEL; PROTEIN-KINASE-C; ENDOGENOUSLY EXPRESSED TRP1; PANCREATIC ACINAR-CELLS; MUCOLIPIDOSIS TYPE-IV; SMOOTH-MUSCLE CELLS; GATED ION CHANNELS AB The transient receptor potential (TRP) family of ion channels is composed of more than 50 functionally versatile cation-permeant ion channels expressed in most mammalian cell types. Considerable research has been brought to bear on the members of this family, especially with regard to their possible role as store-operated calcium channels, although studies have provided evidence that TRP channels exhibit a number of regulatory and functional aspects. Enclogenclus and transiently expressed TRP channels can be activated by different mechanisms grouped into four main categories: receptor-ope rated activation, store depletion-mediated activation, ligand-induced activation, and direct activation. This article reviews the biochemical characteristics of the different members of the TRP family and summarizes their involvement in a number of physiological events ranging from sensory transduction to development, which might help in understanding the relationship between TRP channel dysfunction and the development of several diseases. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge, England. Univ Extremadura, Dept Physiol, Caceres, Spain. RP Woodard, GE (reprint author), NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015; OI rosado, juan/0000-0002-9749-2325; Sage, Stewart/0000-0001-8578-3558 NR 213 TC 6 Z9 6 U1 1 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 BN 978-0-12-373700-7 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2007 VL 256 BP 35 EP + DI 10.1016/S0074-7696(07)56002-X PG 34 WC Cell Biology SC Cell Biology GA BFS73 UT WOS:000244386100002 PM 17241904 ER PT S AU Anantharaman, V Iyer, LM Balaji, S Aravind, L AF Anantharaman, Vivek Iyer, Lakshminarayan M. Balaji, S. Aravind, L. BE Jeon, KW TI Adhesion molecules and other secreted host-interaction determinants in apicomplexa: Insights from comparative genomics SO INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 262 SE INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY LA English DT Review; Book Chapter DE apicomplexa; apicomplexan parasitism; adhesions; alveolate extrusion; hematozoans; protein export ID PARASITE PLASMODIUM-FALCIPARUM; HUMAN MALARIA PARASITE; PARASITOPHOROUS VACUOLE MEMBRANE; GDP-FUCOSE TRANSPORTER; MASS RHOPTRY PROTEIN; GROWTH FACTOR-LIKE; TOXOPLASMA-GONDII; INFECTED ERYTHROCYTES; BINDING-PROTEIN; GENE FAMILY AB Apicomplexa have developed distinctive adaptations for invading and surviving within animal cells. Here a synthetic overview of the diversity and evolutionary history of cell membrane-associated, -secreted, and -exported proteins related to apicomplexan parasitism is presented. A notable feature in this regard was the early acquisition of adhesion protein domains and glycosylation systems through lateral transfer from animals. These were utilized in multiple contexts, including invasion of host cells and parasite-specific developmental processes. Apicomplexans possess a specialized version of the ancestral alveolate extrusion machinery, the rhoptries and micronemes, which are deployed in invasion and delivery of proteins into host cells. Each apicomplexan lineage has evolved a unique spectrum of extruded proteins that modify host molecules in diverse ways. Hematozoans, in particular, appear to have evolved novel systems for export of proteins into the host organelles and cell membrane during intracellular development. These exported proteins are an important aspect of the pathogenesis of Plasmodium and Theileria, being involved in response to fever and in leukocyte proliferation respectively. The complement of apicomplexan surface proteins has primarily diversified via massive lineage-specific expansions of certain protein families, which are often coded by subtelomeric gene arrays. Many of these families have been found to be central to immune evasion, Domain shuffling and accretion have resulted in adhesins with new domain architectures. In terms of individual genes, constant selective pressures from the host immune response has resulted in extensive protein polymorphisms and gene losses. Apicomplexans have also evolved complex regulatory mechanisms controlling expression and maturation of surface proteins at the chromatin, transcriptional, posttranscriptional, and posttranslational levels. Evolutionary reconstruction suggests that the ancestral apicomplexan had thrombospondin and EGF domain adhesins, which were linked to the parasite cytoskeleton, and played a central role in invasion through formation of the moving junction. It also suggests that the ancestral parasite had O-linked glycosylation of surface proteins which was partially or entirely lost in hematozoan lineages. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Anantharaman, V (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. OI Anantharaman, Vivek/0000-0001-8395-0009 FU Intramural NIH HHS NR 160 TC 33 Z9 33 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7696 BN 978-0-12-374167-7 J9 INT REV CYTOL JI Int.Rev.Cytol. PY 2007 VL 262 BP 1 EP 74 DI 10.1016/S0074-7696(07)62001-4 PG 74 WC Cell Biology SC Cell Biology GA BGM17 UT WOS:000248299700001 PM 17631186 ER PT J AU Szatmari, P White, J Merikangas, KR AF Szatmari, Peter White, Julie Merikangas, Kathleen R. TI The use of genetic epidemiology to guide classification in child and adult psychopathology SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Review ID PERVASIVE DEVELOPMENTAL DISORDERS; AUTISM DIAGNOSTIC INTERVIEW; GENERALIZED ANXIETY DISORDER; INFLAMMATORY-BOWEL-DISEASE; QUANTITATIVE TRAIT LOCUS; GENOME-WIDE ASSOCIATION; ASPERGER-SYNDROME; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; ENDOPHENOTYPE CONCEPT AB The goal of this paper is to illustrate the application of the tools of genetic epidemiology, particularly the family study method, to inform the classification of psychiatric disorders in adults and children. The first section describes family studies of adults designed to investigate the causes of comorbidity of anxiety and depression. The analysis of familial traits provides stronger evidence for the validity of certain sub-types of anxiety and mood disorders that co-occur within the same individual and within families. The second section presents an example of the use of the family study method to examine the validity of the autism spectrum disorders (ASD). A review of these studies suggests that the most consistently familial traits in ASD are language and communication skills, insistence on sameness and non-verbal IQ. These are also the traits most commonly associated with the differentiation of autism from Asperger disorder and PDDNOS using both cross- sectional and longitudinal studies. From these data, a new classification system of the ASDs is proposed based on these familial traits. C1 McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. RP Szatmari, P (reprint author), McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. EM szatmar@mcmaster.ca NR 124 TC 21 Z9 21 U1 3 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PY 2007 VL 19 IS 5 BP 483 EP 496 DI 10.1080/09540260701563619 PG 14 WC Psychiatry SC Psychiatry GA 223PX UT WOS:000250385900003 PM 17896229 ER PT J AU Nygaard, I Handa, V Brubaker, L Borello-France, D Wei, J Wells, E Weber, AM AF Nygaard, Ingrid Handa, Vicki Brubaker, Linda Borello-France, Diane Wei, John Wells, Ellen Weber, Anne M. CA Pelvic Floor Disorders Network TI Physical activity in women planning sacrocolpopexy SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE pelvic organ prolapse; sacrocolpopexy; physical activity; exercise ID PELVIC ORGAN PROLAPSE; FLOOR DYSFUNCTION AB This study describes preoperative physical activity in 314 stress-continent women with prolapse planning sacrocolpopexy. Seventy-six percent reported that they engaged in mild, 60% in moderate, and 26% in strenuous exercise (counts are not mutually exclusive). Activity frequencies did not generally differ by prolapse stage. Prolapse substantially interfered with exercise or recreation in 27% of women, household work or yard work in 19%, and work outside the home in 8%. Compared to women with less symptom distress, more women with greater symptom distress reported that prolapse interfered with household/yard work (43 vs 5%, p < 0.0001), working outside the home (29 vs 8%, p < 0.005), and recreation/exercise (51 vs 10%, p < 0.0001). Prolapse stage was not associated with interference with household/yard work (p=0.28) or work outside home (p=0.89). Although prolapse stage is associated with interference with recreation (p=0.02), this association is not consistently positive : stage II, 42%; stage III, 22%; and stage IV, 32%. C1 Univ Utah, Coll Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. Johns Hopkins Univ, Dept Obstet & Gynecol, Baltimore, MD USA. Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Duquesne Univ, Dept Phys Therapy, Pittsburgh, PA 15219 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. NICHHD, Bethesda, MD 20892 USA. RP Nygaard, I (reprint author), Univ Utah, Coll Med, Dept Obstet & Gynecol, 30 North 1900 East,Room 2B 242, Salt Lake City, UT 84132 USA. EM Ingrid.nygaard@hsc.utah.edu FU NICHD NIH HHS [U10 HD41263, U10 HD41268, U10 HD41261, U10 HD41250, U01 HD41249, U10 HD41267, U10 HD41269, U10 HD41248] NR 13 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD JAN PY 2007 VL 18 IS 1 BP 33 EP 37 DI 10.1007/s00192-006-0116-8 PG 5 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 109GJ UT WOS:000242295600007 PM 16688397 ER PT J AU Ghavami, S Hashemi, M de Serres, FJ Bajestani, SN Mehrabifar, H Leonardi, A AF Ghavami, Saeid Hashemi, Mohammad de Serres, Fredrick J. Bajestani, Saeed Naghibzadeh Mehrabifar, Hamid Leonardi, Andrea TI Trypsin inhibitory capacity in vernal keratoconjunctivitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PLASMA ALPHA-1-PROTEINASE INHIBITOR; MAST-CELL CHYMASE; ALPHA-1-ANTITRYPSIN DEFICIENCY; ALLERGIC CONJUNCTIVITIS; PROTEINASE-INHIBITORS; MOLECULAR-BASIS; SERUM-ALBUMIN; ANGIOTENSIN-I; TEAR; CONVERSION AB PURPOSE. To study tear trypsin inhibitory capacity (T-TIC), serum trypsin inhibitory capacity (S-TIC) and their relationship to matrix metalloproteinases (MMP)-1 and -9 in patients with vernal keratoconjunctivitis (VKC). METHODS. In the first phase of the study, inactivation of alpha-1 antitrypsin (AAT) by MMP-1 and -9 was investigated in vitro. Subsequently, tear samples were collected after clinical evaluation from 14 patients with active VKC and 15 normal control subjects. Tear cytology was performed on all samples. Levels of T-TIC and S-TIC were determined by spectrophotometry, whereas levels of tear pro-MMP-1, pro-MMP-9, and active MMP-1 and -9 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS. MMP-1 and -9 inactivated AAT in vitro. S-TIC was significantly higher (P < 0.0001), and T-TIC (P < 0.0001) significantly lower in VKC samples. Tear levels of pro-MMP-1 and pro-MMP-9, and the activity of MMP-1 and -9 was significantly greater in patients with VKC than in healthy subjects (P < 0.0001). There was no significant correlation between T-TIC, MMP-1, and MMP-9 activity. In addition, T-TIC was not correlated to the total clinical score or to single clinical sign scores. CONCLUSIONS. In this study, tear trypsin inhibitory capacity was shown to be reduced and tear MMP-1 and -9 activity increased in patients with VKC. Although T-TIC did not correlate with VKC severity, a local reduced inhibitory capacity of ATT may facilitate or prolong conjunctival inflammation in VKC. C1 Zahedan Univ Med Sci, Dept Clin Biochem, Sch Med, Zahedan, Iran. Zahedan Univ Med Sci, Res Ctr Infect Dis & Trop Med, Zahedan, Iran. Manitoba Inst Cell Biol, Canc Care Manitoba, Winnipeg, MB R3E 0V9, Canada. NIEHS, Ctr Evaluat Risks Human Reprod, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. Univ Padua, Dept Ophthalmol, Padua, Italy. RP Leonardi, A (reprint author), Dept Neurosci, Ophthalmol Unit, Via Giustiniani 2, I-35128 Padua, Italy. EM andrea.leonardi@unipd.it RI Hashemi, Mohammad/H-2446-2016; Ghavami, Saeid/Q-8918-2016 OI Hashemi, Mohammad/0000-0002-6074-7101; NR 52 TC 6 Z9 9 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2007 VL 48 IS 1 BP 264 EP 269 DI 10.1167/iovs.06-0758 PG 6 WC Ophthalmology SC Ophthalmology GA 124GC UT WOS:000243355100035 PM 17197542 ER PT J AU Jia, LH Liu, ZB Sun, LJ Miller, SS Ames, BN Cotman, CW Liu, JK AF Jia, Lihong Liu, Zhongbo Sun, Lijuan Miller, Sheldon S. Ames, Bruce N. Cotman, Carl W. Liu, Jiankang TI Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: Protection by (R)-alpha-lipoic acid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; ALPHA-LIPOIC ACID; AGE-RELATED LOSS; MACULAR DEGENERATION; LIPID-PEROXIDATION; ARPE-19 CELLS; RISK-FACTORS; INHIBITION; STRESS; DECAY AB PURPOSE. To understand better the cell and molecular basis for the epidemiologic association between cigarette smoke, oxidant injury, and age-associated macular degeneration, the authors examined the effects of acrolein, a major toxicant in cigarette smoke, on oxidative mitochondrial damage in retinal pigment epithelial (RPE) cells and the reduction of this damage by lipoic acid. METHODS. Cultured human ARPE19 cells and primary cultures of human fetal (hf)RPE were treated with acrolein. The toxicity of acrolein and the protective effects of R-alpha-lipoic acid were examined with a variety of previously described techniques. RESULTS. Acute acrolein exposure exceeding 50 mu M (24 hours) in ARPR19 cells caused toxicity, including decreases in cell viability, mitochondrial potential, GSH, antioxidant capacity, Nrf2 expression, enzyme activity (mitochondrial complexes I, II, III; superoxide dismutase; and glutathione peroxidase). Acute exposure also increased oxidant levels, protein carbonyls, and calcium. Continuous acrolein exposure over 8 or 32 days caused similar toxicity but from 10- to 100-fold lower doses (0.1-5 mu M). Pretreatment with R-alpha-lipoic acid effectively protected ARPE-19 cells from acrolein toxicity. Primary hfRPE cells were comparable to the ARPE-19 cells in sensitivity to acrolein toxicity and lipoic acid protection. CONCLUSIONS. These results show that acrolein is a mitochondrial toxicant in RPE cells and that acrolein-induced oxidative mitochondrial dysfunction is reduced by lipoic acid. The similar sensitivity of the ARPE-19 and hfRPE cells suggests that both models are useful for studying RPE toxicity and protection. These experiments indicate that mitochondria-targeted antioxidants such as lipoic acid may be an effective strategy for reducing or preventing chronic oxidant-induced RPE degeneration in vivo from a variety of sources, including cigarette smoke. C1 Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Chinese Acad Sci, Inst Nutrit Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. NEI, NIH, Bethesda, MD 20892 USA. RP Liu, JK (reprint author), Univ Calif Irvine, Inst Brain Aging & Dementia, 1261 Gillespie Neurosci Res Facil, Irvine, CA USA. EM j.liu@uci.edu RI Liu, Jiankang/A-1610-2011 FU NEI NIH HHS [EY0160101, R21 EY016101, R21 EY016101-01A1, R21 EY016101-02] NR 41 TC 89 Z9 94 U1 5 U2 10 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 JAN PY 2007 VL 48 IS 1 BP 339 EP 348 DI 10.1167/iovs.06-0248 PG 10 WC Ophthalmology SC Ophthalmology GA 124GC UT WOS:000243355100045 PM 17197552 ER PT J AU Amaral, MEJ Owens, KE Elliott, JS Fickey, C Schaffer, AA Agarwala, R Womack, JE AF Amaral, M. E. J. Owens, K. E. Elliott, J. S. Fickey, C. Schaeffer, A. A. Agarwala, R. Womack, J. E. TI Construction of a river buffalo (Bubalus bubalis) whole-genome radiation hybrid panel and preliminary RH mapping of chromosomes 3 and 10 SO ITALIAN JOURNAL OF ANIMAL SCIENCE LA English DT Article DE River buffalo; Whole genome; Radiation hybrid panel; Gene mapping AB The buffalo (Bubalus bubalis) not only is a useful source of milk, it also provides meat and works as a natural source of labor and biogas. To establish a project for buffalo genome mapping a 5,000-rad whole genome radiation hybrid panel was constructed for river buffalo and used to build preliminary RH maps from two chromosomes (BBU 3 and BBU10). The preliminary maps contain 66 markers, including coding genes, cattle ESTs and microsatellite loci. The RH maps presented here are the starting point for mapping additional loci, in particular, genes and expressed sequence tags that will allow detailed comparative maps between buffalo, cattle and other species to be constructed. A large quantity of DNA has been prepared from the cell lines forming the RH panel reported here and will be made publicly available to the international community both for the study of chromosome evolution and for the improvement of traits important to the role of buffalo in animal agriculture. C1 [Amaral, M. E. J.] UNESP Sao Paulo State Univ, IBILCE, Dept Biol, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil. [Owens, K. E.; Elliott, J. S.; Fickey, C.; Womack, J. E.] Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX 77843 USA. [Schaeffer, A. A.; Agarwala, R.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Amaral, MEJ (reprint author), UNESP Sao Paulo State Univ, IBILCE, Dept Biol, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil. EM eamaral@ibilce.unesp.br NR 45 TC 0 Z9 1 U1 0 U2 0 PU PAGEPRESS PUBL PI PAVIA PA MEDITGROUP, VIA G BELLI, 4, PAVIA, 27100, ITALY SN 1594-4077 J9 ITAL J ANIM SCI JI Ital. J. Anim. Sci. PY 2007 VL 6 SU 2 BP 237 EP 245 PN 1 PG 9 WC Agriculture, Dairy & Animal Science; Agriculture, Multidisciplinary; Veterinary Sciences SC Agriculture; Veterinary Sciences GA V12KP UT WOS:000207598400028 ER PT J AU Stafuzza, NB Ianella, P Miziara, MN Agarwala, R Schaffer, AA Riggs, PK Womack, JE Amaral, MEJ AF Stafuzza, N. Bonvino Ianella, P. Miziara, M. Nunes Agarwala, R. Schaeffer, A. A. Riggs, P. K. Womack, J. E. Amaral, M. E. J. TI Preliminary comparative RH mapping between river buffalo chromosome 6 (BBU6) and bovine chromosome 3 (BTA3) SO ITALIAN JOURNAL OF ANIMAL SCIENCE LA English DT Article C1 [Stafuzza, N. Bonvino; Ianella, P.; Miziara, M. Nunes; Amaral, M. E. J.] UNESP, Sao Paulo State Univ, IBILCE, Dept Biol, Sao Jose Do Rio Preto, Brazil. [Agarwala, R.; Schaeffer, A. A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Riggs, P. K.] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. [Womack, J. E.] Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX USA. RP Amaral, MEJ (reprint author), Univ Estadual Paulista, UNESP Sao Jose, Sao Paulo, Brazil. EM eamaral@ibilce.unesp.br RI Schaffer, Alejandro/F-2902-2012; Amaral, Elisabete/K-9246-2013; Riggs, Penny/A-8192-2008; Ianella, Patricia/A-2444-2016 OI Riggs, Penny/0000-0003-3296-320X; Ianella, Patricia/0000-0002-6651-2987 NR 0 TC 0 Z9 0 U1 1 U2 2 PU PAGEPRESS PUBL PI PAVIA PA MEDITGROUP, VIA G BELLI, 4, PAVIA, 27100, ITALY SN 1594-4077 J9 ITAL J ANIM SCI JI Ital. J. Anim. Sci. PY 2007 VL 6 SU 2 BP 425 EP 425 PN 1 PG 1 WC Agriculture, Dairy & Animal Science; Agriculture, Multidisciplinary; Veterinary Sciences SC Agriculture; Veterinary Sciences GA V12KP UT WOS:000207598400073 ER PT J AU Labunskyy, VM Hatfield, DL Gladyshev, VN AF Labunskyy, Vyacheslav M. Hatfield, Dolph L. Gladyshev, Vadim N. TI The Sep15 protein family: Roles in disulfide bond formation and quality control in the endoplasmic reticulum SO IUBMB LIFE LA English DT Review DE selenoprotein; disulfide bond formation; endoplasmic reticulum; protein folding; thiol-disulfide oxidoreductase ID CALRETICULIN P-DOMAIN; GLYCOPROTEIN GLUCOSYLTRANSFERASE; RIBONUCLEASE B; UDP-GLUCOSE; CALNEXIN; THIOREDOXIN; ERP57; SELENOPROTEIN; CHAPERONE; OXIDOREDUCTASES AB Disulfide bonds play an important role in the structure and function of membrane and secretory proteins. The formation of disulfide bonds in the endoplasmic reticulum ( ER) of eukaryotic cells is catalyzed by a complex network of thiol-disulfide oxidoreductases. Whereas a number of ER-resident oxidoreductases have been identified, the function of only a few of them is firmly established. Recently, a selenocysteine-containing oxidoreductase, Sep15, has been implicated in disulfide bond assisted protein folding, and a role in quality control for this selenoprotein has been proposed. This review summarizes up-to-date information on the Sep15 family proteins and highlights new insights into their physiological function. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, Sect Mol Biol Selenium, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS; NCI NIH HHS [CA 080946] NR 30 TC 49 Z9 50 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PY 2007 VL 59 IS 1 BP 1 EP 5 DI 10.1080/15216540601126694 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 145UM UT WOS:000244890900001 PM 17365173 ER PT J AU Eaton, WA Henry, ER Hofrichter, J Bettati, S Viappiani, C Mozzarelli, A AF Eaton, William A. Henry, Eric R. Hofrichter, James Bettati, Stefano Viappiani, Cristiano Mozzarelli, Andrea TI Evolution of allosteric models for hemoglobin SO IUBMB LIFE LA English DT Review DE hemeproteins; hemoglobin; protein function; protein structure; structural biology ID COOPERATIVE FREE-ENERGIES; 3-DIMENSIONAL FOURIER SYNTHESIS; TERTIARY STRUCTURAL-CHANGE; T STATE HEMOGLOBIN; OXYGEN-BINDING; LIGAND-BINDING; EXPERIMENTAL RESOLUTION; INOSITOL HEXAPHOSPHATE; QUATERNARY STRUCTURE; SINGLE-CRYSTALS AB yWe compare various allosteric models that have been proposed to explain cooperative oxygen binding to hemoglobin, including the two- state allosteric model of Monod, Wyman, and Changeux ( MWC), the Cooperon model of Brunori, the model of Szabo and Karplus ( SK) based on the stereochemical mechanism of Perutz, the generalization of the SK model by Lee and Karplus ( SKL), and the Tertiary Two- State ( TTS) model of Henry, Bettati, Hofrichter and Eaton. The preponderance of experimental evidence favors the TTS model which postulates an equilibrium between high ( r)- and low ( t)a. nity tertiary conformations that are present in both the T and R quaternary structures. Cooperative oxygenation in this model arises from the shift of T to R, as in MWC, but with a signifi. cant population of both r and t conformations in the liganded T and in the unliganded R quaternary structures. The TTS model may be considered a combination of the SK and SKL models, and these models provide a framework for a structural interpretation of the TTS parameters. The most compelling evidence in favor of the TTS model is the nanosecond - millisecond carbon monoxide ( CO) rebinding kinetics in photodissociation experiments on hemoglobin encapsulated in silica gels. The polymeric network of the gel prevents any tertiary or quaternary conformational changes on the sub- second time scale, thereby permitting the subunit conformations prior to CO photodissociation to be determined from their ligand rebinding kinetics. These experiments show that a large fraction of liganded subunits in the T quaternary structure have the same functional conformation as liganded subunits in the R quaternary structure, an experimental. finding inconsistent with the MWC, Cooperon, SK, and SKL models, but readily explained by the TTS model as rebinding to r subunits in T. We propose an additional experiment to test another key prediction of the TTS model, namely that a fraction of subunits in the unliganded R quaternary structure has the same functional conformation ( t) as unliganded subunits in the T quaternary structure. C1 NIH, NIDDK, Phys Chem Lab, Bethesda, MD 20892 USA. Univ Parma, Dept Biochem & Mol Biol, I-43100 Parma, Italy. Univ Parma, Dept Phys, I-43100 Parma, Italy. RP Eaton, WA (reprint author), NIH, NIDDK, Phys Chem Lab, Bldg 5, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov RI Henry, Eric/J-3414-2013; Mozzarelli, Andrea/C-3615-2014; OI Henry, Eric/0000-0002-5648-8696; Mozzarelli, Andrea/0000-0003-3762-0062; Viappiani, Cristiano/0000-0001-7470-4770 FU Intramural NIH HHS NR 74 TC 71 Z9 71 U1 3 U2 21 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PY 2007 VL 59 IS 8-9 BP 586 EP 599 DI 10.1080/15216540701272380 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 199UT UT WOS:000248721400014 PM 17701554 ER PT J AU Fields, J Hanisch, JJ Choi, JW Hwang, PM AF Fields, Jerad Hanisch, Jesse J. Choi, Jeong W. Hwang, Paul M. TI How does p53 regulate mitochondrial respiration? SO IUBMB LIFE LA English DT Editorial Material ID CYTOCHROME-C-OXIDASE; TUMOR-SUPPRESSOR; OXIDATIVE-PHOSPHORYLATION; HUMAN SCO1; CANCER; DEFICIENCY; EXPRESSION; APOPTOSIS; CELLS; MUTATIONS C1 NHLBI, NIH, Cardiol Branch, Bethesda, MD 20892 USA. RP Hwang, PM (reprint author), NHLBI, NIH, Cardiol Branch, Bldg 10, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov FU Intramural NIH HHS NR 28 TC 4 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PY 2007 VL 59 IS 10 BP 682 EP 684 DI 10.1080/15216540601185021 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 213CL UT WOS:000249643400008 PM 18027443 ER PT J AU Follmann, D Duerr, A Tabet, S Gilbert, P Moodie, Z Fast, P Cardinali, M Self, S AF Follmann, Dean Duerr, Ann Tabet, Stephen Gilbert, Peter Moodie, Zoe Fast, Patricia Cardinali, Massimo Self, Steve TI Endpoints and regulatory issues in HIV vaccine clinical trials - Lessons from a workshop SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE clinical trials; epidemiology; HIV vaccine; surrogate endpoint ID VIRAL LOAD; EFFICACY; INFECTION; SURVIVAL; REDUCTION; COUNTRIES; DESIGN; AIDS; RNA AB A successful HIV vaccine would have a substantial impact on acquisition of infection, progression of disease among the infected, or infectiousness of the infected. Current vaccine candidates are anticipated to have their major effect on viremia, however, with the expectation that this would induce or be concordant with a reduced rate of AIDS, death, or infectiousness. Although direct assessment of disease progression or infectiousness may be impractical, available potential surrogates for these endpoints may be misleading. This article summarizes the proceedings of a National Institute of Allergy and Infectious Disease-sponsored workshop to explore the use of surrogate endpoints for licensure of an HIV vaccine. Early, medium, and late endpoints were discussed, along with challenges such as surrogate validity, the confounding effect of antiretroviral therapy initiation, and potential selection bias in the vaccine and placebo recipients who become infected. Results from 5 hypothetic HIV vaccine clinical trials with ambiguously successful results were presented to an expert panel for interpretation and discussion of next steps. Key recommendations included assessing magnitude and durability of surrogate effects, generalization across populations, and directed improvement of vaccines. Use of acquisition and a postinfection surrogate as coprimary endpoints was supported, along with use of composite endpoints and exploration of heterogeneity in vaccine efficacy by characteristics of the host and virus. C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Stat Ctr HIV AIDS Res & Prevent, Seattle, WA USA. Int AIDS Vaccine Initiat, New York, NY USA. Henry Jackson Fdn, Bethesda, MD USA. RP Follmann, D (reprint author), NIAID, Biostat Res Branch, 67000B Rockledge Dr,MSC 7609, Bethesda, MD 20892 USA. EM dfollmann@Niaid.nih.gov FU NIAID NIH HHS [R37 AI029168-18] NR 27 TC 8 Z9 8 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 JAN 1 PY 2007 VL 44 IS 1 BP 49 EP 60 DI 10.1097/01.qai.0000247227.22504.ce PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 121XD UT WOS:000243189400008 PM 17075387 ER PT J AU Bryant, AS Leighty, RM Shen, XL Read, JS Brouwers, P Turpin, DB LaRussa, PS Pacheco-Acosta, E Paul, ME Vajaranant, M Tuomala, RE AF Bryant, Allison S. Leighty, Robert M. Shen, XianLin Read, Jennifer S. Brouwers, Pim Turpin, Delmyra B. LaRussa, Philip S. Pacheco-Acosta, Edna Paul, Mary E. Vajaranant, Mark Tuomala, Ruth E. CA Women Infants Transmission Study TI Predictors of repeat pregnancy among HIV-1-infected women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; predictors; repeat pregnancy ID IMMUNODEFICIENCY-VIRUS SEROSTATUS; INFECTION; IMPACT AB Background: In the Women and Infants Transmission Study (WITS), a prospective cohort study of HIV-infected pregnant women at six US mainland and Puerto Rican sites, changes in the HIV-1 epidemic have included higher income, better education, and better-controlled HIV disease among more recently enrolled women. Because these changes may alter the reproductive patterns of these women an awareness of these women's current reproductive behaviors is essential. We examined predictors of repeat pregnancy among HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS). Methods: Women enrolled in WITS without a history of sterilization were included. Using bivariate and multivariate analyses, predictors of a repeat pregnancy were modeled. Changes in risk factors for repeat pregnancy over time were examined and important predictors of repeat pregnancy were determined. Results: Of 2246 eligible women, 22% had more than one WITS-enrolled pregnancy. In bivariate analyses, risk of repeat pregnancy was associated with younger age, lower educational status, higher CD4%, and lower viral loads. There was little change in risk factors for repeat pregnancy over time. Conclusions: HIV-1-infected women who are younger and healthier are more likely to have more than one pregnancy. Factors associated with repeat pregnancy among HIV-1-infected women have remained stable over time. Awareness of these factors will better equip healthcare providers to address the reproductive needs of HIV-1-infected women. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. C TASC, Baltimore, MD USA. NICHHD, Bethesda, MD USA. Baylor Coll Med, Houston, TX 77030 USA. NIMH, Rockville, MD 20857 USA. Univ Illinois, Chicago, IL 60680 USA. Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. Univ Puerto Rico, San Juan, PR 00936 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bryant, AS (reprint author), Univ Calif San Francisco, 505 Parnassus Ave,Box 0132, San Francisco, CA 94143 USA. EM bryanta@obgyn.ucsf.edu NR 14 TC 12 Z9 12 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 JAN 1 PY 2007 VL 44 IS 1 BP 87 EP 92 DI 10.1097/01.qai.0000243116.14165.52 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 121XD UT WOS:000243189400013 PM 17091023 ER PT J AU Murray, MM Li, TK AF Murray, Margaret M. Li, Ting-Kai TI Expanding the role of the generalist nurse in the prevention and treatment of alcohol use disorder SO JOURNAL OF ADDICTIONS NURSING LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE USE DISORDERS; BRIEF INTERVENTIONS; TRAUMA CENTER; EMERGENCY-DEPARTMENT; PRIMARY-CARE; FOLLOW-UP; DRINKERS; SERVICES; CONSUMPTION C1 [Murray, Margaret M.; Li, Ting-Kai] NIAAA, NIH, Bethesda, MD USA. RP Murray, MM (reprint author), NIAAA, NIH, Bethesda, MD USA. NR 31 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1088-4602 J9 J ADDICT NURS JI J. Addict. Nurs. PY 2007 VL 18 IS 4 BP 163 EP 165 DI 10.1080/10884600701699495 PG 3 WC Substance Abuse; Nursing SC Substance Abuse; Nursing GA 246EW UT WOS:000251991300002 ER PT J AU Goldstein, RB Asarnow, JR Jaycox, LH Shoptaw, S Murray, PJ AF Goldstein, Rise B. Asarnow, Joan R. Jaycox, Lisa H. Shoptaw, Steven Murray, Pamela J. TI Correlates of "non-problematic" and "problematic" substance use among depressed adolescents in primary care SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE depression; adolescents; primary care; substance abuse ID NATIONAL-COMORBIDITY-SURVEY; RANDOMIZED CONTROLLED-TRIAL; MANAGED PRIMARY-CARE; MENTAL-HEALTH; UNITED-STATES; USE DISORDERS; PSYCHIATRIC-DISORDERS; ALCOHOL-USE; EATING-DISORDERS; DUAL DIAGNOSIS AB Substance use and related problems were assessed in a sample of primary care patients (n = 450) ages 13-21 who screened positive for depression at a clinic visit. Patients were classified as having no substance use (n = 248), non-problematic use (substance use without reported school, work, social, or family problems, n = 90), or use that reportedly caused problems in at least one area (n = 112). In logistic regression models, older age, externalizing symptoms, and not being African American were significantly associated with non-problematic use; older age, male gender, externalizing symptoms, Caucasian/White ethnicity/race., and more friends were associated with problematic use. Odds ratios were similar for patients reporting non-problematic and problematic use, suggesting that, in the presence of depression, any substance use merits evaluation and monitoring to determine treatment needs and to prevent escalation of dysfunction. C1 Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. RAND Corp, Arlington, VA USA. Univ Calif Los Angeles, Dept Family Med & Psychiat & Behav Sci, Los Angeles, CA USA. Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Natl Inst Hlth, 5635 Fishers Lane,Room 3068,MS 9304, Bethesda, MD 20892 USA. EM goldster@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU AHRQ HHS [HS09908]; NIMH NIH HHS [P30 MH068639] NR 75 TC 2 Z9 2 U1 5 U2 7 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2007 VL 26 IS 3 BP 39 EP 52 DI 10.1300/J069v26n03_05 PG 14 WC Substance Abuse SC Substance Abuse GA 203RX UT WOS:000248992800005 PM 18018807 ER PT J AU Martins, SS Copersino, ML Soderstrom, CA Smith, GS Dischinger, PC McDuff, DR Hebel, JR Kerns, TJ Ho, SM Read, KM Gorelick, DA AF Martins, Silvia S. Copersino, Marc L. Soderstrom, Carl A. Smith, Gordon S. Dischinger, Patricia C. McDuff, David R. Hebel, J. Richard Kerns, Timothy J. Ho, Shiu M. Read, Kathleen M. Gorelick, David A. TI Sociodemographic characteristics associated with substance use status in a trauma inpatient population SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE trauma patients; substance abuse; sociodemographic characteristics; treatment programs ID BRIEF MOTIVATIONAL INTERVENTION; DISORDERS IDENTIFICATION TEST; ALCOHOL EPIDEMIOLOGIC SURVEY; NATIONAL-COMORBIDITY-SURVEY; UNITED-STATES; EMERGENCY-ROOM; DRUG-USE; 12-MONTH PREVALENCE; DEPENDENCE; ABUSE AB Substance use is significantly associated with physical injury, yet relatively little is known about the prevalence of specific substance use disorders among trauma patients, or their associated sociodemographic characteristics. We evaluated these issues in an unselected sample of 1, 118 adult inpatients at the University of Maryland Shock Trauma Center, Baltimore, MD, who were interviewed with the psychoactive substance use disorder section of the Structured Clinical Interview for DSM-III-R. Among trauma inpatients, lifetime alcohol users (71.8% of subjects) were more likely male; users of illegal drugs (45.3%) were also more likely to be younger, unmarried, and poor. Patients with current drug abuse/dependence (18.8%) were more likely to be non-white, less educated, and poor; those with current alcohol abuse/dependence (32.1%) were also more likely male, unmarried, and older. These findings highlight the need for screening for substance use disorders in trauma settings and referral of patients to substance abuse treatment programs. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. Univ Maryland, Sch Med, Natl Study Ctr Trauma & Emergency Med Syst, Baltimore, MD 21201 USA. Liberty Mutual Res Inst Safety, Hopkinton, MA 01748 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Natl Study Ctr Trauma & Emergency Med Syst, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Epidemiol, Baltimore, MD 21201 USA. RP Gorelick, DA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM DGORELIC@intra.nida.nih.gov RI Martins, Silvia/A-6898-2008; Martins, Silvia/C-9405-2014; OI Smith, Gordon/0000-0002-2911-3071 FU Intramural NIH HHS; NIAAA NIH HHS [R01-AA09050, R01 AA009050] NR 48 TC 4 Z9 4 U1 2 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2007 VL 26 IS 2 BP 53 EP 62 DI 10.1300/J069v26n02_07 PG 10 WC Substance Abuse SC Substance Abuse GA 186CD UT WOS:000247755800007 PM 17594998 ER PT J AU Martins, SS Copersino, ML Soderstrom, CA Smith, GS Dischinger, PC McDuff, DR Hebel, JR Kerns, TJ Ho, SM Read, KM Gorelick, DA AF Martins, Silvia S. Copersino, Marc L. Soderstrom, Carl A. Smith, Gordon S. Dischinger, Patricia C. McDuff, David R. Hebel, J. Richard Kerns, Timothy J. Ho, Shiu M. Read, Kathleen M. Gorelick, David. A. TI Risk of psychoactive substance dependence among substance users in a trauma inpatient population SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE psychoactive substance; trauma inpatient; hallucinogens; substance dependence ID DSM-III-R; EMERGENCY-ROOM; USE DISORDERS; INJURY RISK; ALCOHOL; PREVALENCE; COCAINE; ABUSE; IV AB One measure of a substance's addictive risk is the proportion of users who become dependent. This study evaluates the lifetime and current risk of substance dependence among lifetime substance users among trauma inpatients and provides a relative ranking of addictive risk among the substances. Data on use of 8 substance groups (alcohol, opiates, cannabis, cocaine, other stimulants, sedative-hypnotics, hallucinogens, other drugs) were obtained by interview (Structured Clinical Interview for the DSM-III-R) from 1, 118 adult trauma inpatients. Prevalence of lifetime dependence among lifetime users ranged from 80.7% for opiates and 70.9% for cocaine to 33.3% for hallucinogens and 26.6% for sedative-hypnotics. The rank order of addictive risk was similar to that found in the general population. Trauma inpatients had a higher absolute addictive risk than the general population, comparable to the risk found in patients in treatment for substance use disorders, suggesting the importance of screening trauma inpatients for substance dependence. C1 US Dept HHS, Intramural Res Program, NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. NIDA, Intramural Res Program, NIH, Baltimore, MD USA. Univ Maryland, Natl Study Ctr Trauma & Emergency Med Syst, Baltimore, MD USA. Liberty Mutual Res Inst Safety, Hopkinton, MA USA. Johns Hopkins Univ, Ctr Injury Res & Policy, Baltimore, MD USA. Univ Maryland, Sch Med, Natl Study Ctr Trauma & Emergency Med Syst, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD USA. RP Gorelick, DA (reprint author), US Dept HHS, Intramural Res Program, NIA, NIH, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. EM DGORELIC@intra.nida.nih.gov RI Martins, Silvia/A-6898-2008; Martins, Silvia/C-9405-2014; OI Smith, Gordon/0000-0002-2911-3071 FU NIAAA NIH HHS [R01 AA009050, R01AA09050] NR 27 TC 2 Z9 2 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2007 VL 26 IS 1 BP 71 EP 77 DI 10.1300/J069v26n01_09 PG 7 WC Substance Abuse SC Substance Abuse GA 151LK UT WOS:000245291600009 PM 17439870 ER PT J AU Krantz, MJ Rowan, SB Schmittner, J Bartelson, BB AF Krantz, Mori J. Rowan, Shane B. Schmittner, John Bartelson, Becki Bucher TI Physician awareness of the cardiac effects of methadone: Results of a national survey SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE methadone; QT prolongation; torsade de pointes; arrhythmia; national survey ID TORSADE-DE-POINTES; MYOCARDIAL-INFARCTION; USERS; REPOLARIZATION; PROLONGATION; PATIENT AB Background: Levacetylmethadol was withdrawn from the U.S. market as a treatment for opioid-dependent patients in 2003 due to QT prolongation, leaving methadone as the primary therapy for over 200,000 individuals. Methadone was subsequently shown to prolong the QT interval as well. We hypothesized that opioid treatment program physicians are unaware of these safety concerns. Methods: To assess awareness of methadone's QT-prolonging properties, we conducted a national mail survey of physicians licensed as medical directors for accredited U.S. opioid treatment programs in 2006. The primary outcome was knowledge of methadone's QT-prolonging effects. Awareness of the cardiac effects of levacetylmethadol and buprenorphine were also assessed. Results: The Survey response rate was 66% (692 physicians) of whom 35% were family practitioners, 25% internists, 22% psychiatrists, and 8% self-identified as addiction specialists. While75% (95% CI, 72-78) correctly identified levacetylmethadol as a QT-prolonging drug, only 4 1% (95% CI, 37-45) were aware of methadone's QT-prolonging properties. Just 24% (95% CI, 21-27) were aware of methadone's association with torsade de pointes. In addition, 52% (95% Cl, 48-56) correctly reported the absence of an association between buprenorphine and QT prolongation. Larger program census and academic setting tended to predict greater awareness of methadone's QT-prolonging effects; yet even in these subgroups awareness did not exceed 54%. Conclusions: Scientific publication alone has been inadequate in raising awareness regarding methadone's QT-prolonging properties, eve In among those who most often prescribe the drug. Universal education initiatives for all accredited opioid treatment programs seem warranted to enhance the safety of this essential therapy. doi: 10.1300/J069v26n04_10 [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-HAWORTH. E-mail address: docdelivery@haworthpress.com Website: http://www.HaworthPress.com (c) 2007 by The Haworth Press, Inc. All rights reserved.]. C1 Denver Hlth Med Ctr, Div Cardiol, Dept Med, Denver, CO 80204 USA. Vanderbilt Univ, Nashville, TN 37240 USA. NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, NIH, Bethesda, MD USA. RP Krantz, MJ (reprint author), Denver Hlth Med Ctr, Div Cardiol, Dept Med, Mail Code 0960,777 Bannock St, Denver, CO 80204 USA. EM Mkrantz@dhha.org NR 26 TC 13 Z9 13 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2007 VL 26 IS 4 BP 79 EP 85 DI 10.1300/J069v26n04_10 PG 7 WC Substance Abuse SC Substance Abuse GA 212BX UT WOS:000249569700010 PM 18032235 ER PT J AU Goldberger, BA Graham, NA Nelson, SJ Cadet, JL Gold, MS AF Goldberger, Bruce A. Graham, Noni A. Nelson, Stephen J. Cadet, Jean Lud Gold, Mark S. TI A marked increase in cocaine-related deaths in the state of Florida: Precursor to an epidemic? SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE cocaine abuse; epidemic; Florida; public health intervention AB The history of cocaine misuse includes a destructive epidemic during the 1980s. While recent surveys suggest cocaine use is stable or decreasing, we have observed increasing trends of cocaine-related death through analysis of medical examiner data collected by the Florida Department of Law Enforcement (FDLE). Florida's per capita cocaine-related death rates nearly doubled from 2001 to 2005. Electronic collection of data such as that collected by the FDLE nationally and in real-time would greatly advance understanding of drug-use, patterns and consequences. For example, results from Florida suggest that high school and college students, and members of higher socioeconomic status, appear to be at increased risk of cocaine abuse. Public health interventions are necessary to prevent another full-fledged epidemic. C1 Univ Florida, Coll Med, Dept Psychiat, Gainesville, FL 32610 USA. Florida Dept Law Enforcement, Med Examiners Commiss, Tallahassee, FL USA. NIDA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL 32611 USA. Univ Florida, Coll Med, Dept Anesthesiol, Gainesville, FL 32611 USA. Univ Florida, Coll Med, Dept Community Hlth & Family Med, Gainesville, FL 32611 USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32611 USA. Univ Florida, McKnight Brain Inst, Div Addict Med, Gainesville, FL 32611 USA. RP Gold, MS (reprint author), Univ Florida, Coll Med, Dept Psychiat, POB 100183, Gainesville, FL 32610 USA. EM msgold@ufl.edu NR 16 TC 3 Z9 4 U1 1 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2007 VL 26 IS 3 BP 113 EP 116 DI 10.1300/J069v26n03_13 PG 4 WC Substance Abuse SC Substance Abuse GA 203RX UT WOS:000248992800013 PM 18018815 ER PT J AU Gergen, PJ Apter, AJ AF Gergen, Peter J. Apter, Andrea J. TI Unconventional risk factors: Another pathway to understanding health disparities SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material DE asthma; disparities; adherence; morbidity ID INNER-CITY ASTHMA; CHILDHOOD ASTHMA; PEDIATRIC ASTHMA; ADHERENCE; CHILDREN; CARE; NONCOMPLIANCE; ENVIRONMENT; DEPRESSION; MORBIDITY C1 NIAID, Div Allergy Immunol & Clin Immunol, NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Gergen, PJ (reprint author), NIAID, Div Allergy Immunol & Clin Immunol, NIH, 6610 Rockledge Dr,Rm 3067, Bethesda, MD 20892 USA. EM pgergen@niaid.nih.gov FU NHLBI NIH HHS [HL073932, HL04337] NR 25 TC 5 Z9 5 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 BP 165 EP 167 DI 10.1016/j.jaci.2006.10.032 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 127YL UT WOS:000243622200023 PM 17141856 ER PT J AU Rotrosen, D Plaut, M Hackett, C Fauci, AS AF Rotrosen, Daniel Plaut, Marshall Hackett, Charles Fauci, Anthony S. TI The National Institute of Allergy and Infectious Diseases' asthma research programs: A retrospective - The early years (1971-1990) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID INNER-CITY CHILDREN; IMMUNOTHERAPY; MORBIDITY C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Rotrosen, D (reprint author), 6610 Rockledge Dr,Room 3111, Bethesda, MD 20817 USA. EM drotrosen@niaid.nih.gov NR 11 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 BP 258 EP 262 DI 10.1016/j.jaci.2006.10.011 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 127YL UT WOS:000243622200045 PM 17376372 ER PT J AU Anmuth, DM Edwards, MS Tatevian, N Holland, SM Hanson, IC AF Anmuth, D. M. Edwards, M. S. Tatevian, N. Holland, S. M. Hanson, I. C. TI Intrathoracic disease and nontuberculous mycobacteria (NTM) in a 6 month old female: Immunodeficiency or bad luck? Case report/proposal SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Anmuth, D. M.; Edwards, M. S.; Tatevian, N.; Hanson, I. C.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX USA. [Holland, S. M.] NIAID, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 709 BP S181 EP S181 DI 10.1016/j.jaci.2006.12.072 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401094 ER PT J AU Gao, L Grant, A Chi, P Gao, P Stockton, M Watson, H Hansel, NN Diette, G Dunston, G Mathias, RA Togias, A Brower, R Sevransky, J Maloney, JP Moss, M Shanholtz, C Garcia, JGN Beaty, TH Barnes, KC AF Gao, L. Grant, A. Chi, P. Gao, P. Stockton, M. Watson, H. Hansel, N. N. Diette, G. Dunston, G. Mathias, R. A. Togias, A. Brower, R. Sevransky, J. Maloney, J. P. Moss, M. Shanholtz, C. Garcia, J. G. N. Beaty, T. H. Barnes, K. C. TI Myosin light chain kinase (MYLK) variants that confer increased risk of sepsis and acute lung injury are associated with asthma and associated phenotypes SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Gao, L.; Grant, A.; Chi, P.; Gao, P.; Stockton, M.; Barnes, K. C.] Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. [Hansel, N. N.; Diette, G.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Dunston, G.] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA. [Mathias, R. A.] NHGRI, Baltimore, MD USA. [Maloney, J. P.; Moss, M.] Univ Colorado, Hlth Sci Ctr, Div Pulm & Crit Care Med, Denver, CO USA. [Shanholtz, C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Garcia, J. G. N.] Univ Chicago Biol Sci, Dept Med, Chicago, IL USA. [Beaty, T. H.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RI Garcia, Joe/E-8862-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 577 BP S146 EP S147 DI 10.1016/j.jaci.2006.11.511 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400576 ER PT J AU Gao, P Grigoryev, D Breslin, L Cheadle, C Mathias, RA Beaty, TH Togias, A Barnes, K AF Gao, P. Grigoryev, D. Breslin, L. Cheadle, C. Mathias, R. A. Beaty, T. H. Togias, A. Barnes, K. TI Keratins: Important candidate genes for asthma and immune responsiveness to cockroach SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Gao, P.; Grigoryev, D.; Breslin, L.; Cheadle, C.; Togias, A.; Barnes, K.] JHAAC, Baltimore, MD USA. [Mathias, R. A.; Beaty, T. H.] Ctr Inherited Dis Res, NIH, Baltimore, MD USA. [Beaty, T. H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 690 BP S176 EP S176 DI 10.1016/j.jaci.2006.12.052 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401075 ER PT J AU Gelfand, EW Salt, B Jain, A Niemela, JE Deering, R Pan-dey, R Quinones, R Orange, J AF Gelfand, E. W. Salt, B. Jain, A. Niemela, J. E. Deering, R. Pan-dey, R. Quinones, R. Orange, J. TI NEMO (IKK gamma) mutation can be associated with opportunistic infection without impairing TLR function SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Gelfand, E. W.; Salt, B.] Natl Jewish Med & Res Ctr, Denver, CO USA. [Jain, A.; Niemela, J. E.] Natl Inst Hlth, Bethesda, MD USA. [Deering, R.; Pan-dey, R.; Orange, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Quinones, R.] Childrens Hosp, Denver, CO 80218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 55 BP S15 EP S15 DI 10.1016/j.jaci.2006.11.074 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400056 ER PT J AU Gendapodi, PR Kioi, M Puri, RK Abel, P Townley, RG AF Gendapodi, P. R. Kioi, M. Puri, R. K. Abel, P. Townley, R. G. TI Effect of IL-13 and IL-13 mutant (IL-13E13K) on airway Hyperresponsive ness (AHR) and airway smooth muscle (ASM) in mice SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Gendapodi, P. R.; Abel, P.; Townley, R. G.] Creighton Univ, Omaha, NE 68178 USA. [Kioi, M.; Puri, R. K.] NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 538 BP S136 EP S137 DI 10.1016/j.jaci.2006.11.663 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400537 ER PT J AU Ishmael, FT Fang, X Heller, N Fan, J Blackshear, PJ Atasoy, U Cheadle, C Stellato, C AF Ishmael, F. T. Fang, X. Heller, N. Fan, J. Blackshear, P. J. Atasoy, U. Cheadle, C. Stellato, C. TI Role of the RNA-binding protein tristetraprolin (TTP) in glucocorticoid (GC)-mediated gene regulation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Ishmael, F. T.; Fang, X.; Heller, N.; Fan, J.; Cheadle, C.; Stellato, C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Blackshear, P. J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Atasoy, U.] Univ Missouri, Columbia, MO USA. RI Stellato, Cristiana/P-3001-2015 OI Stellato, Cristiana/0000-0002-1294-8355 NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 528 BP S134 EP S134 DI 10.1016/j.jaci.2006.11.653 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400527 ER PT J AU Kim, N Foster, BA Prussin, C AF Kim, N. Foster, B. A. Prussin, C. TI Identification of cytokine heterogeneity within the Th2 subset SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Kim, N.; Foster, B. A.; Prussin, C.] NIH, NIAID, Lab Allergic Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 369 BP S94 EP S94 DI 10.1016/j.jaci.2006.11.584 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400369 ER PT J AU Naccara, L Heymann, P Carter, M Litonjua, A Peters, E Satinover, S Erwin, E Platts-Mills, TAE AF Naccara, L. Heymann, P. Carter, M. Litonjua, A. Peters, E. Satinover, S. Erwin, E. Platts-Mills, T. A. E. TI Prevalence and titer of specific IgE antibodies in relation to total serum IgE: Evaluation of sensitization to allergens derived from domestic mice SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Naccara, L.; Heymann, P.; Satinover, S.; Erwin, E.; Platts-Mills, T. A. E.] Univ Virginia, Med Ctr, Charlottesville, VA USA. [Carter, M.] NIH, NIAID, Bethesda, MD 20892 USA. [Litonjua, A.] Harvard Med Ctr, Boston, MA USA. [Peters, E.] Allergy & Asthma Consultants, Austin, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 1033 BP S264 EP S264 DI 10.1016/j.jaci.2006.12.402 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401416 ER PT J AU Pero, RS Borchers, MT Spicher, K Ochkur, SI Sikora, L Rao, SP O'Neill, KR Abdala-Valencia, H Shen, H Simon, MI McGarry, MP Lee, NA Cook-Mills, JM Sriramarao, P Birnbaumer, L Lee, JJ AF Pero, R. S. Borchers, M. T. Spicher, K. Ochkur, S. I. Sikora, L. Rao, S. P. O'Neill, K. R. Abdala-Valencia, H. Shen, H. Simon, M. I. McGarry, M. P. Lee, N. A. Cook-Mills, J. M. Sriramarao, P. Birnbaumer, L. Lee, J. J. TI Extravasation of leukocytes from circulations is controlled by G alpha(i2) signaling events in the endothelium SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Pero, R. S.; Ochkur, S. I.; O'Neill, K. R.; McGarry, M. P.; Lee, N. A.; Lee, J. J.] Mayo Clin Arizona, Scottsdale, AZ USA. [Borchers, M. T.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Spicher, K.] Univ Dusseldorf, D-4000 Dusseldorf, Germany. [Sikora, L.; Rao, S. P.; Sriramarao, P.] La Jolla Inst Mol Med, San Diego, CA USA. [Abdala-Valencia, H.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Shen, H.] Zhejiang Univ, Coll Med, Hangzhou 310027, Peoples R China. [Simon, M. I.] CALTECH, Pasadena, CA 91125 USA. [Birnbaumer, L.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 598 BP S152 EP S152 DI 10.1016/j.jaci.2006.11.532 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400597 ER PT J AU Pomes, A Li, M Wuenschmann, S Chapman, MD Wlodawer, A Gustchina, A AF Pomes, A. Li, M. Wuenschmann, S. Chapman, M. D. Wlodawer, A. Gustchina, A. TI Cockroach allergen Bla g 2 dimerizes in a crystal complex with an antibody fragment SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Pomes, A.; Wuenschmann, S.; Chapman, M. D.] INDOOR Biotechnol Inc, Charlottesville, VA USA. [Li, M.] SAIC Frederick, Basic Res Program, Frederick, MD USA. [Wlodawer, A.; Gustchina, A.] Natl Canc Inst, Macromol Crystallog Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 410 BP S104 EP S104 DI 10.1016/j.jaci.2006.11.625 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400410 ER PT J AU Rosenwasser, LJ Schwartz, LB Sheikh, J Klion, AD Rothenberg, ME AF Rosenwasser, L. J. Schwartz, L. B. Sheikh, J. Klion, A. D. Rothenberg, M. E. CA Mepolizumab HES Study TI Corticosteroid-sparing effects of Mepolizumab, an anti-interleukin-5 monoclonal antibody, in patients with hypereosinophilic syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Rosenwasser, L. J.] Childrens Mercy Hosp, Div Allergy Immunol, Kansas City, MO 64108 USA. [Schwartz, L. B.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23284 USA. [Sheikh, J.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Klion, A. D.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. [Rothenberg, M. E.] Childrens Hosp, Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45229 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 628 BP S160 EP S160 DI 10.1016/j.jaci.2006.11.564 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401013 ER PT J AU Sever, ML Arbes, SJ Zeldin, DC Schal, C Santangelo, RG Gore, JC Vaughn, B Mitchell, H AF Sever, M. L. Arbes, S. J., Jr. Zeldin, D. C. Schal, C. Santangelo, R. G. Gore, J. C. Vaughn, B. Mitchell, H. TI Cockroach allergen reduction by extermination alone in low-income, urban homes-a randomized control trial SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Sever, M. L.; Arbes, S. J., Jr.; Zeldin, D. C.] NIEHS, Res Triangle Pk, NC USA. [Schal, C.; Santangelo, R. G.; Gore, J. C.] NSCU, Raleigh, NC USA. [Vaughn, B.; Mitchell, H.] Rho Inc, Chapel Hill, NC USA. RI Schal, Coby/A-8717-2010 OI Schal, Coby/0000-0001-7195-6358 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 618 BP S157 EP S157 DI 10.1016/j.jaci.2006.11.554 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401003 ER PT J AU Stellato, C Fang, X Tancowny, B Fan, J Wu, F Asaki, SY De Fanis, U Huang, S Gorospe, M Atasoy, U Casolaro, V AF Stellato, C. Fang, X. Tancowny, B. Fan, J. Wu, F. Asaki, S. Y. De Fanis, U. Huang, S. Gorospe, M. Atasoy, U. Casolaro, V. TI Role of the RNA-binding protein HuR in posttranscriptional regulation of IL-13 in T cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Stellato, C.; Fang, X.; Tancowny, B.; Fan, J.; Wu, F.; Asaki, S. Y.; De Fanis, U.; Huang, S.; Casolaro, V.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Gorospe, M.] NIH, Natl Inst Aging, Baltimore, MD USA. [Atasoy, U.] Univ Missouri, Columbia, MO USA. RI Casolaro, Vincenzo/E-9144-2010; Stellato, Cristiana/P-3001-2015 OI Casolaro, Vincenzo/0000-0001-9810-0488; Stellato, Cristiana/0000-0002-1294-8355 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 526 BP S133 EP S133 DI 10.1016/j.jaci.2006.11.651 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400525 ER PT J AU Tran, D Shevach, EM AF Tran, D. Shevach, E. M. TI TGF-beta stimulated human CD4+CD25-FOXP3-cells express FOXP3, but lack regulatory function SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Tran, D.; Shevach, E. M.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 1205 BP S309 EP S309 DI 10.1016/j.jaci.2006.12.578 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401588 ER PT J AU Trivedi, S Hodges, MG Bundoc, V Norris, HH Boesen, A Madala, S Urban, JF Keane-Myers, A AF Trivedi, S. Hodges, M. G. Bundoc, V. Norris, H. H. Boesen, A. Madala, S. Urban, J. F. Keane-Myers, A. TI Ascaris antigens suppress experimental allergic inflammation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Trivedi, S.; Hodges, M. G.; Bundoc, V.; Boesen, A.; Madala, S.; Keane-Myers, A.] NIH, NIAID, LAD, Rockville, MD USA. [Norris, H. H.] NIH, NIAID, Rockville, MD USA. [Urban, J. F.] USDA, NRFL, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 523 BP S133 EP S133 DI 10.1016/j.jaci.2006.11.648 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400522 ER PT J AU Wang, J Visness, CM Calatroni, A Gergen, PJ Mitchell, HE Sampson, HA AF Wang, J. Visness, C. M. Calatroni, A. Gergen, P. J. Mitchell, H. E. Sampson, H. A. TI Association of environmental allergen sensitization with asthma morbidity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Wang, J.; Sampson, H. A.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Visness, C. M.; Calatroni, A.; Mitchell, H. E.] Rho Fed Syst Div Inc, Chapel Hill, NC USA. [Gergen, P. J.] NIH, NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 663 BP S169 EP S169 DI 10.1016/j.jaci.2006.12.025 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401048 ER PT J AU Watkins, RS MacDowell, AL Fontana-Penn, M De Ravin, S Malech, HL AF Watkins, R. S. MacDowell, A. L. Fontana-Penn, M. De Ravin, S. Malech, H. L. TI 14 year old boy with ill-defined immunodeficiency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Watkins, R. S.; MacDowell, A. L.; Fontana-Penn, M.] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [De Ravin, S.; Malech, H. L.] NIAID, NIH, Bethesda, MD 20892 USA. RI MacDowell, Alastair/K-4211-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 723 BP S184 EP S184 DI 10.1016/j.jaci.2006.12.086 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401108 ER PT J AU Wu, H Romieu, I Sienra-Monge, J Rio-Navarro, B Anderson, DM Dunn, EW Steiner, LL Lara-Sanchez, I London, S AF Wu, H. Romieu, I. Sienra-Monge, J. Rio-Navarro, B. Anderson, D. M. Dunn, E. W. Steiner, L. L. Lara-Sanchez, I. London, S. TI Parental smoking modifies effects of genetic variation in tumor necrosis factor-alpha on childhood asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Wu, H.; Dunn, E. W.; London, S.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Romieu, I.; Lara-Sanchez, I.] Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. [Sienra-Monge, J.; Rio-Navarro, B.] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. [Steiner, L. L.] Roche Mol Syst, Alameda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 660 BP S168 EP S168 DI 10.1016/j.jaci.2006.12.022 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460401045 ER PT J AU Wuenschmann, S Li, M Gustchina, A Wlodawer, A Chapman, M Pomes, A AF Wuenschmann, S. Li, M. Gustchina, A. Wlodawer, A. Chapman, M. Pomes, A. TI Mapping of antigenic determinants on Bla g 2 surface SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 23-27, 2007 CL San Diego, CA SP Amer Acad Allergy, Asthma & Immunol C1 [Wuenschmann, S.; Chapman, M.; Pomes, A.] INDOOR Biotechnol Inc, Charlottesville, VA USA. [Li, M.] SAIC, Basic Res Program, Frederick, MD USA. [Gustchina, A.] NCI, Macromol Crystallog Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2007 VL 119 IS 1 SU 1 MA 412 BP S105 EP S105 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 238PT UT WOS:000251460400412 ER PT J AU Fabene, PF Farace, P Brambilla, P Andreone, N Cerini, R Pelizza, L Versace, A Rambaldelli, G Birbaumer, N Tansella, M Sbarbati, A AF Fabene, Paolo F. Farace, Paolo Brambilla, Paolo Andreone, Nicola Cerini, Roberto Pelizza, Luisa Versace, Amelia Rambaldelli, Gianluca Birbaumer, Niels Tansella, Michele Sbarbati, Andrea TI Three-dimensional MRI perfusion maps: a step beyond volumetric analysis in mental disorders SO JOURNAL OF ANATOMY LA English DT Article DE brain perfusion; Gadolinium; schizophrenia; segmentation; time-to-peak ID CEREBRAL-BLOOD-FLOW; SCHIZOPHRENIC-PATIENTS; ONSET SCHIZOPHRENIA; HMPAO SPECT; STROKE AB A new type of magnetic resonance imaging analysis, based on fusion of three-dimensional reconstructions of time-to-peak parametric maps and high-resolution T1-weighted images, is proposed in order to evaluate the perfusion of selected volumes of interest. Because in recent years a wealth of data have suggested the crucial involvement of vascular alterations in mental diseases, we tested our new method on a restricted sample of schizophrenic patients and matched healthy controls. The perfusion of the whole brain was compared with that of the caudate nucleus by means of intrasubject analysis. As expected, owing to the encephalic vascular pattern, a significantly lower time-to-peak was observed in the caudate nucleus than in the whole brain in all healthy controls, indicating that the suggested method has enough sensitivity to detect subtle perfusion changes even in small volumes of interest. Interestingly, a less uniform pattern was observed in the schizophrenic patients. The latter finding needs to be replicated in an adequate number of subjects. In summary, the three-dimensional analysis method we propose has been shown to be a feasible tool for revealing subtle vascular changes both in normal subjects and in pathological conditions. C1 Univ Verona, Fac Med, Dept Morphol & Biomed Sci, Sect Anat & Histol, I-37134 Verona, Italy. Univ Verona, Dept Med & Publ Hlth, Sect Psychiat & Clin Psychol, I-37134 Verona, Italy. Univ Verona, Sect Radiol, Dept Morphol & Biomed Sci, I-37134 Verona, Italy. Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. NINDS, Human Cort Physiol, NIH, Bethesda, MD 20892 USA. RP Fabene, PF (reprint author), Univ Verona, Fac Med, Dept Morphol & Biomed Sci, Sect Anat & Histol, Strada Grazie 8, I-37134 Verona, Italy. EM paolo@anatomy.univr.it RI brambilla, paolo/B-4184-2010; Tansella, Michele/B-4106-2010; Rambaldelli, Gianluca/E-5939-2010 OI brambilla, paolo/0000-0002-4021-8456; Farace, Paolo/0000-0002-6051-2345; Rambaldelli, Gianluca/0000-0001-6921-6553 NR 28 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-8782 J9 J ANAT JI J. Anat. PD JAN PY 2007 VL 210 IS 1 BP 122 EP 128 DI 10.1111/j.1469-7580.2006.00659.x PG 7 WC Anatomy & Morphology SC Anatomy & Morphology GA 119PB UT WOS:000243023100013 PM 17229290 ER PT J AU Billal, DS Fedorko, DP Yan, SS Hotomi, M Fujihara, K Nelson, N Yamanaka, N AF Billal, Dewan S. Fedorko, Daniel P. Yan, S. Steve Hotomi, Muneki Fujihara, Keiji Nelson, Nancy Yamanaka, Noboru TI In vitro induction and selection of fluoroquinolone-resistant mutants of Streptococcus pyogenes strains with multiple emm types SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE S pyogenes; resistance; laboratory induction and selection; point mutations ID REDUCED SUSCEPTIBILITY; STAPHYLOCOCCUS-AUREUS; TOPOISOMERASE-IV; CLONAL SPREAD; DNA GYRASE; PNEUMONIAE; MUTATIONS; PARC; QUINOLONES; ISOLATE AB Objectives: To perform a systematic analysis of point mutations in the quinolone resistance determining regions (QRDRs) of the DNA gyrase and topoisomerase genes of emm type 6 and other emm types of Streptococcus pyogenes strains after in vitro exposure to stepwise increasing concentrations of levofloxacin. Methods: Twelve parent strains of S. pyogenes, each with a different emm type, were chosen for stepwise exposure to increasing levels of levofloxacin followed by selection of resistant mutants. The QRDRs of gyrA, gyrB, parC and parE correlating to mutants with increased MICs were analysed for point mutations. Results: Multiple mutants with significantly increased MICs were generated from each strain. The amino acid substitutions identified were consistent regardless of emm type and were similar to the mechanisms of resistance reported in clinical isolates of S. pyogenes. The number of induction/selection cycles required for the emergence of key point mutations in gyrA and parC was variable among strains. For each parent-mutant set, when MIC increased, serine-81 of gyrA and serine-79 of parC were the primary targets for amino acid substitutions. No point mutations were found in the QRDRs of gyrB and parE in any of the resistant mutants sequenced. Conclusions: Despite its intrinsic polymorphism in the QRDR of parC, emm type 6 is not more likely to develop high-level resistance to fluoroquinolones when compared with other emm types. All emm types seem equally inducible to high-level fluoroquinolone resistance. C1 Wakayama Med Univ, Dept Otolaryngol Head & Neck Surg, Wakayama 6418510, Japan. NIH, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. US FDA, Dept Hlth & Human Serv, Rockville, MD 20855 USA. RP Yamanaka, N (reprint author), Wakayama Med Univ, Dept Otolaryngol Head & Neck Surg, 811-1 Kimiidera, Wakayama 6418510, Japan. EM ynobi@wakayama-med.ac.jp NR 22 TC 13 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JAN PY 2007 VL 59 IS 1 BP 28 EP 34 DI 10.1093/jac/dkl428 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 120FJ UT WOS:000243069600004 PM 17065188 ER PT J AU Bondell, HD Liu, A Schisterman, EF AF Bondell, Howard D. Liu, Aiyi Schisterman, Enrique F. TI Statistical inference based on pooled data: A moment-based estimating equation approach SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE pooling biospecimens; set-based observations; moments; Box-Cox transformation; goodness-of-fit; lognormal distribution ID ROC CURVE; TRANSFORMATION MODELS; ESTIMATING PREVALENCE; DISEASE; EFFICIENCY; TESTS; HIV AB We consider statistical inference on parameters of a distribution when only pooled data are observed. A moment-based estimating equation approach is proposed to deal with situations where likelihood functions based on pooled data are difficult to work with. We outline the method to obtain estimates and test statistics of the parameters of interest in the general setting. We demonstrate the approach on the family of distributions generated by the Box-Cox transformation model, and, in the process, construct tests for goodness of fit based on the pooled data. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. RP Liu, A (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 29 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0266-4763 EI 1360-0532 J9 J APPL STAT JI J. Appl. Stat. PY 2007 VL 34 IS 2 BP 129 EP 140 DI 10.1080/02664760600994844 PG 12 WC Statistics & Probability SC Mathematics GA 192LZ UT WOS:000248204600001 ER PT J AU Court, DL Oppertheim, AB Adhya, SL AF Court, Donald L. Oppertheim, Amos B. Adhya, Sankar L. TI A new look at bacteriophage lambda genetic networks SO JOURNAL OF BACTERIOLOGY LA English DT Review ID LYSIS-LYSOGENY DECISION; PHAGE-LAMBDA; TRANSCRIPTION ANTITERMINATION; ESCHERICHIA-COLI; RNA-POLYMERASE; N-PROTEIN; INT GENE; TRANSLATION REPRESSION; PROPHAGE INDUCTION; COLIPHAGE-LAMBDA C1 NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91010 Jerusalem, Israel. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Court, DL (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Bldg 539,POB B, Frederick, MD 21702 USA. EM court@ncifcrf.gov FU Intramural NIH HHS NR 69 TC 67 Z9 68 U1 2 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2007 VL 189 IS 2 BP 298 EP 304 DI 10.1128/JB.01215-06 PG 7 WC Microbiology SC Microbiology GA 125OY UT WOS:000243452800004 PM 17085553 ER PT J AU Gonzalez, FJ AF Gonzalez, Frank J. TI CYP3A4 and pregnane X receptor humanized mice SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article; Proceedings Paper CT Symposium on Human Metabolic Interactions of Environmental Chemicals CY MAY 23, 2006 CL NC State Univ, Raleigh, NC HO NC State Univ DE cytochrome p450; CYP1A2; CYP3A4; PXR; rifampicin ID TRANSGENIC MICE; CYTOCHROME-P450 3A4; EXPRESSION; MOUSE; METABOLISM; LIVER; GENE; SEX AB Marked species differences exist in P450 expression and activities. In order to produce mouse models that can be used to more accurately predict human drug and carcinogen metabolism, P450- and xenobiotic receptor humanized mice are being prepared using bacterial artificial chromosomes (BAC) and P1 phage artificial chromosomes (PAC) genomic clones. In some cases, transgenic mice carrying the human genes are bred with null-mice to produce fully human- 1A2 CY, Pized mice. Mice expressing human CYP1A1, d CYP A7 were gen3 CYP2E1, CYP2136, CYP3A4, an erated and characterized. Studies with the CYP3A4humanized (hCYP3A4) mouse line revealed new information on the physiological function of this P450 and its role in drug metabolism in vivo. With this mouse line, CYP3A4, under certain circumstances, was found to alter the serum levels of estrogen resulting in deficient lactation and low pup survival as a result of underdeveloped mammary glands. This hCYP3A4 mouse established the importance of intestinal CYP3A4 in the pharmacokinetics of orally administered drugs. The h hCYP3A4 mice were also used to establish the mechanisms of potential gender differences in CYP3A4 expression (adult female > adult male) that could account or human gender differences in drug metabolism and response. The pregnane X receptor (PXR) is also involved in induction of drug metabolism through its target genes including CYP3A4. Since species differences exist in ligand specificity between human and mice, a PXR-humanized mouse (hPXR) was produced that responds to human PXR activators such as rifampicin but does not respond to the rodent activator pregnenalone 16m-carbonitrile. C1 NIH, NCI, Lab Metab, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NIH, NCI, Lab Metab, Bldg 10, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 16 TC 22 Z9 24 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2007 VL 21 IS 4 BP 158 EP 162 DI 10.1002/jbt.20173 PG 5 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 206SC UT WOS:000249202200002 PM 17936928 ER PT J AU Chao, SL Moss, JM Harry, GJ AF Chao, Shirley L. Moss, Jason M. Harry, G. Jean TI Lead-induced alterations of apoptosis and neurotrophic factor mRNA in the developing rat cortex, hippocampus, and cerebellum SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE lead acetate; apoptosis; neurotrophic factor; cortex; hippocampus; cerebellum; caspase 2; caspase 3; bax; bc1-x; brain-derived neurotrophic factor ID CELL-DEATH; NERVOUS-SYSTEM; EXPOSURE; NEURONS; BRAIN; NEUROTOXICITY; RECEPTORS AB Previous reports have recently shown the prototypic neurotoxicant, lead, to induce apoptosis in the brains of developing organisms. In the current study, timed-pregnant rats were exposed to lead acetate (0.2% in the drinking water) 24 h following birth at postnatal day 1 (PND 1). Dams and pups were continuously exposed to lead through the drinking water of the dam until PND 20. Postnatal exposure in the pups resulted in altered mRNA levels of the following apoptotic and neurotrophic factors: caspase 2 and 3, bax, bc1-x, and brain-derived neurotrophic factor (BDNF). Ribonuclease protection assays were conducted to measure the factors simultaneously at the following postnatal time points: 9, 12, 15, 20, and 25 days. Our results suggest a brain region- and time-specific response following lead acetate exposure. The region most vulnerable to alterations occurs in the hippocampus with alterations beginning at PND 12, in which caspase 3, bcl-x, and BDNF increase with lead exposure. Significant treatment effects were not observed for both the cortex and cerebellum. K) 2007 Wiley Periodicals, Inc. C1 Fayetteville State Univ, Dept Nat Sci, Fayetteville, NC 28301 USA. Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Chao, SL (reprint author), Fayetteville State Univ, Dept Nat Sci, Fayetteville, NC 28301 USA. EM schao@uncfsu.edu FU Intramural NIH HHS [Z01 ES021164-11]; NIEHS NIH HHS [N01-ES-25331]; NIMHD NIH HHS [P20 MD001089-01, P20 MD001089] NR 24 TC 19 Z9 21 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2007 VL 21 IS 5 BP 265 EP 272 DI 10.1002/jbt.20191 PG 8 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 224RV UT WOS:000250465000004 PM 17912701 ER PT J AU Sheehan, FT AF Sheehan, Frances T. TI The finite helical axis of the knee joint (a non-invasive in vivo study using fast-PC MRI) SO JOURNAL OF BIOMECHANICS LA English DT Article DE knee; MRI; finite helical axis ID CRUCIATE LIGAMENT RUPTURE; MOTION ANALYSIS; KINEMATICS; MODEL; STANDARDIZATION; FLUOROSCOPY; AXES AB An understanding of the in vivo knee joint kinematics is critical for the further improvement and validation of knee joint models and for the development of better surgical and rehabilitative protocols. Unfortunately, most studies exploring the finite helical axis (FHA) tend to produce excellent qualitative results, but quantitative results are often lacking. Thus, the purpose of this study was to non-invasively and in vivo quantify the tibiofemoral FHA in a relatively large normal population during volitional knee extension using fast-PC MRI, to report the data relative to consistent coordinate systems (making it available for modeling input, experimental comparison and for device design), to determine the variability of the FHA, to investigate the screw home mechanism and to test the hypothesis that knee joint kinematics are independent of gender. Intra- and inter-subject repeatability was excellent. The intra- (inter-) subject repeatability of the FHA orientation in the frontal and axial planes was 1.8% (3.3%) and 3.7% (6.0%) of the average value, respectively. At the beginning of extension, the FHA was directed laterally and slightly superiorly and at the end of extension, it was directed in the lateral-inferior direction, indicative of the screw-home mechanism. The FHA location was not fixed during extension. There was small, but significant differences in all FHA parameters between genders and normalizing positional data relative to epicondylar width helped to reduce this difference. The data obtained in the current study forms an excellent base for future knee joint modeling and clinical studies. (c) 2006 Published by Elsevier Ltd. C1 NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 20742 USA. RP Sheehan, FT (reprint author), NIH, Phys Disabil Branch, CRC Rm 1-1469,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 NR 27 TC 24 Z9 25 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PY 2007 VL 40 IS 5 BP 1038 EP 1047 DI 10.1016/j.jbiomech.2006.04.006 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 155GH UT WOS:000245565400010 PM 17141789 ER PT J AU Li, WJ Mauck, RL Cooper, JA Yuan, XN Tuan, RS AF Li, Wan-Ju Mauck, Robert L. Cooper, James A. Yuan, Xiaoning Tuan, Rocky S. TI Engineering controllable anisotropy in electrospun biodegradable nanofibrous scaffolds for musculoskeletal tissue engineering SO JOURNAL OF BIOMECHANICS LA English DT Article DE tissue engineering; tensile properties; anisotropy; mechanical testing; biodegradable scaffolds ID ARTICULAR-CARTILAGE; CONFINED COMPRESSION; INTERSTITIAL FLUID; CELL ALIGNMENT; ACL FIBROBLAST; COLLAGEN GELS; STRAIN; ORIENTATION; MENISCI; TENSION AB Many musculoskeletal tissues exhibit significant anisotropic mechanical properties reflective of a highly oriented underlying extracellular matrix. For tissue engineering, recreating this organization of the native tissue remains a challenge. To address this issue, this study explored the fabrication of biodegradable nanofibrous scaffolds composed of aligned fibers via electrospinning onto a rotating target, and characterized their mechanical anisotropy as a function of the production parameters. The characterization showed that nanofiber organization was dependent on the rotation speed of the target; randomly oriented fibers (33% fiber alignment) were produced on a stationary shaft, whereas highly oriented fibers (94% fiber alignment) were produced when rotation speed was increased to 9.3 m/s. Non-aligned scaffolds had an isotropic tensile modulus of 2.1 +/- 0.4 MPa, compared to highly anisotropic scaffolds whose modulus was 11.6 +/- 3.1 MPa in the presumed fiber direction, suggesting that fiber alignment has a profound effect on the mechanical properties of scaffolds. Mechanical anisotropy was most pronounced at higher rotation speeds, with a greater than 33-fold enhancement of the Young's modulus in the fiber direction compared to perpendicular to the fiber direction when the rotation speed reached 8 m/s. In cell culture, both the organization of actin filaments of human mesenchymal stem cells and the cellular alignment of meniscal fibroblasts were dictated by the prevailing nanofiber orientation. This study demonstrates that controllable and anisotropic mechanical properties of nanofibrous scaffolds can be achieved by dictating nanofiber organization through intelligent scaffold design. Published by Elsevier Ltd. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov RI Li, Wan-Ju/A-7002-2008 FU Intramural NIH HHS [NIH0011027684, Z01 AR041131-06]; NIAMS NIH HHS [Z01 AR041131] NR 28 TC 201 Z9 207 U1 3 U2 56 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PY 2007 VL 40 IS 8 BP 1686 EP 1693 DI 10.1016/j.jbiomech.2006.09.004 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 177ZR UT WOS:000247191500005 PM 17056048 ER PT J AU Basalo, IM Chahine, NO Kaplun, M Chen, FH Hung, CT Ateshian, GA AF Basalo, Ines M. Chahine, Nadeen O. Kaplun, Michael Chen, Faye H. Hung, Clark T. Ateshian, Gerard A. TI Chondroitin sulfate reduces the friction coefficient of articular cartilage SO JOURNAL OF BIOMECHANICS LA English DT Article DE cartilage; friction; chondroitin sulfate; osteoarthritis ID INTERSTITIAL FLUID PRESSURIZATION; KNEE OSTEOARTHRITIS; BOUNDARY FRICTION; OSMOTIC-PRESSURE; LUBRICATION; JOINT; TOLERABILITY; DEGRADATION; GLUCOSAMINE; EFFICACY AB The objective of this study was to investigate the effect of chondroitin sulfate (CS)-C on the frictional response of bovine articular cartilage. The main hypothesis is that CS decreases the friction coefficient of articular cartilage. Corollary hypotheses are that viscosity and osmotic pressure are not the mechanisms that mediate the reduction in the friction coefficient by CS. In Experiment 1, bovine articular cartilage samples (n = 29) were tested in either phosphate buffered saline (PBS) or in PBS containing 100 mg/ml of CS following 48 h incubation in PBS or in PBS + 100mg/ml CS (control specimens were not subjected to any incubation). In Experiment 2, samples (n = 23) were tested in four different solutions: PBS, PBS + 100 mg/ml CS, and PBS + polyethylene glycol (PEG) (133 or 170 mg/ml). In Experiment 3, samples (n = 18) were tested in three solutions of CS (0, 10 and 100 mg/ml). Frictional tests (cartilage-on-glass) were performed under constant stress (0.5 MPa) for 3600s and the time-dependent friction coefficient was measured. Samples incubated or tested in a 100mg/ml CS solution exhibited a significantly lower equilibrium friction coefficient than the respective PBS control. PEG solutions delayed the rise in the friction coefficient relative to the PBS control, but did not reduce the equilibrium value. Testing in PBS + 10 mg/ml of CS did not cause any significant decrease in the friction coefficient. In conclusion, CS at a concentration of 100mg/ml significantly reduces the friction coefficient of bovine articular cartilage and this mechanism is neither mediated by viscosity nor osmolarity. These results suggest that direct injection of CS into the joint may provide beneficial tribological effects. (C) 2006 Elsevier Ltd. All rights reserved. C1 Columbia Univ, Dept Mech Engn, New York, NY 10027 USA. Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Ateshian, GA (reprint author), Columbia Univ, Dept Mech Engn, 500 W 120th St,220 SW Mudd,MC 4703, New York, NY 10027 USA. EM ateshian@columbia.edu RI Chahine, Nadeen/O-5496-2015; OI Chahine, Nadeen/0000-0002-0478-6042 FU NIAMS NIH HHS [R01 AR043628, AR43628, R01 AR043628-13] NR 29 TC 34 Z9 34 U1 4 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PY 2007 VL 40 IS 8 BP 1847 EP 1854 DI 10.1016/j.jbiomech.2006.07.007 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 177ZR UT WOS:000247191500025 PM 17084404 ER PT J AU Sheehan, FT AF Sheehan, Frances T. TI The 3D patellar tendon moment arm: Quantified in vivo during volitional activity SO JOURNAL OF BIOMECHANICS LA English DT Article DE tendon; human; knee; tibiofemoral; patellofemoral; MRI ID KNEE-JOINT; FLEXION; KINEMATICS; EXTENSION AB The patellar tendon moment arm is a critical quantity in that it defines the quadriceps ability to generate a moment on the tibia. Thus, the primary purpose of this study was to establish the first in vivo three-dimensional measures of the patellar tendon moment arm, measured non-invasively and in vivo during dynamic activity in a large normative population (n = 34) using a dynamic MRI technique (fast-PC MRI). The magnitude of the moment arm was defined as the shortest distance between the finite helical axis and the patellar tendon line of action. Using these data, the hypothesis that the patellar tendon moment arm is independent of gender was tested. In general, the moment arm increased from 20 to 50 inni during knee extension. There were significant differences (P < 0.05) in the moment arm between gender, but these differences were eliminated when the moment arm was scaled by the femoral epicondylar width. This study took a large step forward towards the ultimate goal of defining how pathology may alter joint dynamics through alteration in moment arms by establishing the first in vivo normative data base for the patellar tendon moment arm using non-invasive measures during volitional activity in a relatively large population (n = 34). The fact that the scaled moment arm was independent of gender may lend insights into impairments that tend to be gender specific, such as patellar maltracking. The next steps will be to quantify the patellar tendon moment arm in populations with specific pathologies. Published by Elsevier Ltd. C1 NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. RP Sheehan, FT (reprint author), NIH, Phys Disabil Branch, Bldg 10,Crc,RM 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM sheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 FU Intramural NIH HHS [Z01 CL060062-04] NR 19 TC 20 Z9 20 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PY 2007 VL 40 IS 9 BP 1968 EP 1974 DI 10.1016/j.jbiomech.2006.09.029 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 185WO UT WOS:000247741300010 PM 17161841 ER PT J AU Lu, XL Miller, C Chen, FH Guo, XE Mow, VC AF Lu, X. Lux Miller, Chester Chen, Faye H. Guo, X. Edward Mow, Van C. TI The generalized triphasic correspondence principle for simultaneous determination of the mechanical properties and proteoglycan content of articular cartilage by indentation SO JOURNAL OF BIOMECHANICS LA English DT Article DE articular cartilage; fixed charge density; mixture theory; triphasic; correspondence principle; indentation ID TENSION-COMPRESSION NONLINEARITY; HYDRATED SOFT-TISSUES; BIPHASIC INDENTATION; STRESS-RELAXATION; MODEL; WATER; VISCOELASTICITY; BEHAVIORS AB The triphasic mixture theory has been used to describe the mechanical and physicochemical behaviors of articular cartilage under some specialized loading conditions. However, the mathematical complexities of this theory have limited its applications for theoretical analyses of experimental studies and models for predicting cartilage and other biological tissues' deformational behaviors. A generalized correspondence principle has been established in the present study, and this principle shows that the equilibrium deformational behavior of a charged-hydrated material under loading is identical to that of an elastic medium without charge. A set of explicit formulas has been derived to correlate the mechanical properties of an equivalent material with the intrinsic elastic moduli, fixed charge density and free-ion concentration within the cartilage tissue. The validity of these formulas is independent of the deformation state of the elastic solid matrix under an infinitesimal strain. Therefore they can be employed for any loading conditions, such as confined or unconfined compression, tension, and indentation tests, etc. In the current study, the fixed charge density of bovine cartilage is determined from the indentation creep data using this generalized correspondence principle. The proteoglycan content results were then compared with those from biochemical assay, yielding a linear regression slope of 1.034. Additionally a correspondence principle within a framework of cubic symmetry and a bilinear response in tension-compression (the conewise linear elasticity model) has also been developed to demonstrate the potential application of current methodology for inhomogeneous, anisotropic and nonlinear situations. (c) 2006 Elsevier Ltd. All rights reserved. C1 Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. Natl Inst Hlth, Cartilage Biol & Orthopaed Branch, Bethesda, MD USA. RP Mow, VC (reprint author), Columbia Univ, Dept Biomed Engn, 351 Engn Terrace,500 W 120th St, New York, NY 10027 USA. EM vem1@columbia.edu NR 35 TC 20 Z9 21 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PY 2007 VL 40 IS 11 BP 2434 EP 2441 DI 10.1016/j.jbiomech.2006.11.015 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 203RB UT WOS:000248990600010 PM 17222852 ER PT J AU Leong, GM Abad, V Charmandari, E Reynolds, JC Hill, S Chrousos, GP Nieman, LK AF Leong, Gary M. Abad, Veronica Charmandari, Evangelia Reynolds, James C. Hill, Suvimol Chrousos, George P. Nieman, Lynnette K. TI Effects of child- and adolescent-onset endogenous Cushing syndrome on bone mass, body composition, and growth: A 7-year prospective study into young adulthood SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE glucocorticoids; Cushing syndrome; bone and fat mass; growth; adiposity ID MINERAL DENSITY; INDUCED OSTEOPOROSIS; HORMONE-SECRETION; SURGICAL CURE; LONG-TERM; DISEASE; ACQUISITION; DIAGNOSIS; TURNOVER; DENSITOMETRY AB The long-term effects on bone and fat mass in children with endogenous CS are unknown. In 14 children followed for 3-7 years into young adulthood after cure of CS, whereas bone mass largely recovered, persisting increases in total body and visceral fat suggests an increase risk of the metabolic syndrome. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Mater Childrens Hosp, Dept Pediat Endocrinol & Diabet, Brisbane, Qld, Australia. Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4067, Australia. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Leong, GM (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. EM gary.leong@mater.org.au RI Charmandari, Evangelia/B-6701-2011 FU Intramural NIH HHS NR 32 TC 34 Z9 36 U1 0 U2 1 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 JAN PY 2007 VL 22 IS 1 BP 110 EP 118 DI 10.1359/JBMR.061010 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 120AR UT WOS:000243056300013 PM 17042737 ER PT J AU Greil, GF Desai, MY Fenchel, M Miller, S Pettigrew, RI Sieverding, L Stuber, M AF Greil, Gerald F. Desai, Milind Y. Fenchel, Michael Miller, Stephan Pettigrew, Roderic I. Sieverding, Ludger Stuber, Matthias TI Reproducibility of free-breathing cardiovascular magnetic resonance coronary angiography SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article DE cardiovascular magnetic resonance; steady state free precession; coronary artery imaging; reproducibility ID MR-ANGIOGRAPHY; NAVIGATOR LOCATIONS; ARTERIES; CONTRAST; VISUALIZATION; EXPERIENCE; DISEASE AB Objective : Contemporary free-breathing non contrast enhanced cardiovascular magnetic resonance angiography (CMRA) was qualitatively and quantitatively evaluated to ascertain the reproducibility of the method for coronary artery luminal dimension measurements. Subjects and Methods : Twenty-two healthy volunteers (mean age 32 +/- 7 years, 12 males) without coronary artery disease were imaged at 2 centers (1 each in Europe and North America) using navigator-gated and corrected SSFP CMRA on a commercial whole body 1.5T System. Repeat images of right (RCA, n = 21), left anterior descending (LAD, n = 14) and left circumflex (LCX, n = 14) coronary arteries were obtained in separate sessions using identical scan protocol and imaging parameters. True visible vessel length, signal-to-noise (SNR), contrast-to-noise ratios (CNR) and the average luminal diameter over the first 4 cm of the vessel were measured. Intra-observer, inter-observer and inter-scan reproducibility of coronary artery luminal diameter were determined using Pearson's correlation, Bland-Altman analysis and intraclass correlation coefficients (ICC). Results : CNR, SNR and the mean length of the RCA, LAD and LCX imaged for original and repeat scans were not significantly different (all p > 0.30). There was a high degree of intra-observer, inter-observer and inter-scan agreements for RCA, LAD and LCX luminal diameter respectively on Bland-Altman and ICC analysis (ICC's for RCA: 0.98. 0.98 and 0.86; LAD: 0.89, 0.89 and 0.63; LCX: 0.95, 0.94 and 0.79). Conclusion : In a 2-center study, we demonstrate that free-breathing 3D SSFP CMRA can visualize long continuous segments of coronary vessels with highly reproducible measurements of luminal diameter. C1 Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. Univ Tubingen, Dept Radiol, Tubeingen, Germany. NIH, Bethesda, MD 20892 USA. Univ Tubingen, Dept Pediat Cardiol, Tubingen, Germany. RP Stuber, M (reprint author), Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, 601 N Caroline St,JHOC 4243, Baltimore, MD 21287 USA. EM mstuber1@jhu.edu RI Stuber, Matthias/B-2949-2010 OI Stuber, Matthias/0000-0001-9843-2028 NR 31 TC 7 Z9 7 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PD JAN-FEB PY 2007 VL 9 IS 1 BP 49 EP 56 DI 10.1080/10976640600897427 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 118VJ UT WOS:000242971300007 PM 17178680 ER PT J AU Bauer, I Al Sarraj, J Vinson, C Larsen, R Thiel, G AF Bauer, Inge Al Sarraj, Jude Vinson, Charles Larsen, Reinhard Thiel, Gerald TI Interleukin-1 beta and tetradecanoylphorbol acetate-induced biosynthesis of tumor necrosis factor alpha in human hepatoma cells involves the transcription factors ATF2 and c-jun and stress-activated protein kinases SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ATF2; c-Jun; MEKK1; MKP-1; p38 protein kinase; TNF alpha promoter ID NF-KAPPA-B; MEK KINASE; IN-VIVO; EMBRYONIC LETHALITY; GENE-TRANSCRIPTION; MAMMALIAN-CELLS; DEFICIENT MICE; GROWTH-FACTOR; PROMOTER; JNK AB The proinflammatory cytokine tumor necrosis factor (TNF) alpha is mainly produced in cells from the monocyte/macrophage lineage. TNF alpha is also a key signaling molecule in the liver functioning as an important physiological and pathogenic mediator. in hepatocytes or human hepatoma cells TNF alpha is expressed at extremely low levels but TNF alpha biosynthesis can be induced by interleukin (IL)-1 beta or 12-O-tetradecanoylphorbol-13-acetate (TPA). Here, we show that IL-1 beta and TPA stimulated TNF alpha gene transcription in hepatoma cells mediated by a composite TPA-responsive element/cAMP response element. Both IL-1 beta and TPA triggered phosphorylation and activation of the basic region leucine zipper transcription factors c-Jun and ATF2 and expression of dominant-negative mutants of c-Jun and ATF2-reduced TNFa promoter activity and secretion of TNFa. Expression of the nuclear dual-specific MAP kinase phosphatase-1 (MKP-1) blocked TNF alpha promoter activity and TNF alpha secretion following IL-1 beta or TPA stimulation, indicating that MKP-1 functions as a nuclear shut-of-device of IL-1 beta and TPA-induced TNF alpha expression. C1 Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. Univ Saarland, Med Ctr, Dept Anesthesiol & Crit Care Med, D-66421 Homburg, Germany. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Thiel, G (reprint author), Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, Bldg 44, D-66421 Homburg, Germany. EM gerald.thiel@uniklinik-saarland.de NR 44 TC 21 Z9 21 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 1 PY 2007 VL 100 IS 1 BP 242 EP 255 DI 10.1002/jcb.21075 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 118RC UT WOS:000242958400020 PM 16888805 ER PT J AU Nagineni, CN Cherukuri, KS Kutty, V Detrick, B Hooks, JJ AF Nagineni, Chandrasekharam N. Cherukuri, Karthik S. Kutty, Veena Detrick, Barbara Hooks, John J. TI Interferon-gamma differentially regulates TGF-beta 1 and TGF-beta 2 expression in human retinal pigment epithelial cells through JAK-STAT pathway SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; PROLIFERATIVE DIABETIC-RETINOPATHY; TUMOR-NECROSIS-FACTOR; TGF-BETA; GENE-EXPRESSION; SUBRETINAL FLUID; TRANSCRIPTION FACTORS; MACULAR DEGENERATION; MESSENGER-RNA; LYMPHOCYTES-T AB Retinal pigment epithelium (RPE) and transforming growth factor-beta (TGF-beta) have been shown to be involved in various retinal diseases. We have studied the role of inflammatory cytokines on the expression and secretion of TGF-beta in human RPE cells (HRPE). Confluent cultures of HRPE derived from donor eyes were used. RT-PCR analyses showed that TNF-alpha and IL-1 beta increased the mRNA levels of both TGF-beta 1 and TGF-beta 2. IFN-gamma enhanced constitutively expressed, as well as, TNF-alpha- and IL-1 beta-induced TGF-beta 1 mRNA levels but decreased TGF-beta 2 mRNA. The effects of these cytokines on TGF-beta 1 and TGF-beta 2 secretion correlated with the mRNA levels. TGF-beta 1 was always produced as the latent form while 21-31% of TGF-beta 2 was in the active form. IFN-gamma reduced the production of active form of TGF-beta 2 to 4-9%. TGF-beta 3 secretion was not detectable under any of the conditions. The Real-Time PCR analysis of TGF-beta mRNAs confirmed the observed results. The TGF-beta 1 and TGF-beta 2 secretion was induced by TGF-beta 2 and TGF-beta 1, respectively. Under these conditions, the contrasting effects of IFN-gamma on TGF-beta 1 and TGF-beta 2 secretion were also observed. JAK inhibitor selectively inhibited IFN-gamma induced TGF-beta 1 secretion and mRNA levels while reversing the inhibitory effects of IFN-gamma on TGF-beta 2. Analyses of transcription factor activity strongly indicated the role of STAT-1 but not NF kappa B,C-Myc,C-Jun,SP-1,MEF-2. Our data demonstrate that IFN-gamma differentially regulates constitutively expressed, as well as, cytokine-incluced TGF-beta 1 and TGF-beta 2 mRNA levels and secretion of TGF-beta s by HRPE. C1 NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 10,Room 10N248, Bethesda, MD 20892 USA. EM hooksj@nei.nih.gov FU Intramural NIH HHS NR 59 TC 29 Z9 30 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2007 VL 210 IS 1 BP 192 EP 200 DI 10.1002/jcp.20839 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 112ZZ UT WOS:000242568200021 PM 17013806 ER PT J AU Bondy, CA AF Bondy, Carolyn A. CA Turner Syndrome Study Grp TI Clinical practice guideline - Care of girls and women with Turner syndrome: A guideline of the Turner Syndrome Study Group SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID GROWTH-HORMONE TREATMENT; SEX-CHROMOSOME ABNORMALITIES; LERI-WEILL DYSCHONDROSTEOSIS; CARDIOVASCULAR RISK-FACTORS; CONGENITAL HEART-DISEASE; RANDOMIZED DOSE-RESPONSE; PULMONARY VENOUS RETURN; POPULATION-BASED COHORT; BONE-MINERAL DENSITY; QUALITY-OF-LIFE AB Objectives: The objective of this work is to provide updated guidelines for the evaluation and treatment of girls and women with Turner syndrome (TS). Participants: The Turner Syndrome Consensus Study Group is a multidisciplinary panel of experts with relevant clinical and research experience with TS that met in Bethesda, Maryland, April 2006. The meeting was supported by the National Institute of Child Health and unrestricted educational grants from pharmaceutical companies. Evidence: The study group used peer-reviewed published information to form its principal recommendations. Expert opinion was used where good evidence was lacking. Consensus: The study group met for 3 d to discuss key issues. Breakout groups focused on genetic, cardiological, auxological, psychological, gynecological, and general medical concerns and drafted recommendations for presentation to the whole group. Draft reports were available for additional comment on the meeting web site. Synthesis of the section reports and final revisions were reviewed by e-mail and approved by whole-group consensus. Conclusions: We suggest that parents receiving a prenatal diagnosis of TS be advised of the broad phenotypic spectrum and the good quality of life observed in TS in recent years. We recommend that magnetic resonance angiography be used in addition to echocardiography to evaluate the cardiovascular system and suggest that patients with defined cardiovascular defects be cautioned in regard to pregnancy and certain types of exercise. We recommend that puberty should not be delayed to promote statural growth. We suggest a comprehensive educational evaluation in early childhood to identify potential attention-deficit or nonverbal learning disorders. We suggest that caregivers address the prospect of premature ovarian failure in an open and sensitive manner and emphasize the critical importance of estrogen treatment for feminization and for bone health during the adult years. All individuals with TS require continued monitoring of hearing and thyroid function throughout the lifespan. We suggest that adults with TS be monitored for aortic enlargement, hypertension, diabetes, and dyslipidemia. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov NR 166 TC 361 Z9 388 U1 3 U2 28 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 JAN PY 2007 VL 92 IS 1 BP 10 EP 25 DI 10.1210/jc.2006-1374 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 123TB UT WOS:000243317500003 PM 17047017 ER PT J AU Waldmann, TA AF Waldmann, Thomas A. TI Anti-tac (daclizumab, zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: A 25-year personal odyssey SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE anti-Tac; adult T-cell leukemia; daclizumab; IL-2 receptor; monoclonal antibody ID T-CELL LEUKEMIA; ANTI-CD25 MONOCLONAL-ANTIBODY; HUMAN INTERLEUKIN-2 RECEPTOR; LIVER-TRANSPLANT RECIPIENTS; NATURAL-KILLER-CELLS; IN-VIVO BLOCKADE; NF-KAPPA-B; IL-2 RECEPTOR; MURINE MODEL; RENAL-TRANSPLANTATION AB Twenty-five years ago, we reported the production of the monoclonal antibody, anti-Tac that identifies the IL-2 receptor alpha subunit and blocks the interaction of IL-2 with this growth factor receptor. In 1997, daclizumab (Zenapax((R))), the humanized form of this antibody, was approved by the FDA for use in the prevention of renal allograft rejection. In addition, we demonstrated that daclizumab is of value in the treatment of patients with noninfectious uveitis, multiple sclerosis, and the neurological disease human T-cell lymphotropic virus I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Others demonstrated therapeutic efficacy with daclizumab in patients with pure red cell aplasia, aplastic anemia, and psoriasis. Thus, translation of basic insights concerning the IL-2/IL-2 receptor system obtained using the monoclonal antibody daclizumab provided a useful strategy for the prevention of organ allograft rejection and the treatment of patients with select autoimmune diseases or T-cell leukemia/lymphoma. C1 NCI, Ctr Canc Res, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Ctr Canc Res, Metab Branch, NIH, NIH Bldg 10,Room 4N115,10 Ctr Dr 1374, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov FU Intramural NIH HHS NR 93 TC 83 Z9 86 U1 2 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JAN PY 2007 VL 27 IS 1 BP 1 EP 18 DI 10.1007/s10875-006-9060-0 PG 18 WC Immunology SC Immunology GA 134OU UT WOS:000244093500001 PM 17216565 ER PT J AU Xie, JRH Zhao, JJ Sun, GY Cioslowski, J AF Xie, John Rui-Hua Zhao, Jijun Sun, Guangyu Cioslowski, Jerzy TI Fluorination approach to achieving tunable-optical-gap and large-optical-gap nanomaterials from carbon-caged nanoparticles SO JOURNAL OF COMPUTATIONAL AND THEORETICAL NANOSCIENCE LA English DT Article DE fullerene; fluorination; optical gap; time-dependent density functional theory; ultraviolet-visible optical absorption; fluorescence; photonics ID SEMICONDUCTOR NANOCRYSTALS; ABSORPTION-SPECTRA; FULLERENES; C-60; C60F18; FLUOROFULLERENES; APPROXIMATION; EXCITATIONS; DERIVATIVES; ENERGY AB We propose a fluorination approach to achieving tunable-optical-gap (TOG) and large-optical-gap (LOG) materials from pure carbon-caged nanoparticles such as fullerenes. Taking the fullerene C-60 as an example, we demonstrate that the optical gap and ultraviolet-visible absorption spectrum of C-60 can be tuned over a broad wavelength range by fluorination. The optical tunability of fluorinated C-60 may be used to design tunable optical devices for a wide range of applications. Among fullerenes obeying isolated pentagon rule, C6o is the only known LOG material with an optical gap appearing in the violet region. Our study shows that fluorinating C-60 can lead to novel LOG nanomaterials, such as C60F20, C60F36, and C60F46 whose optical gaps are located in the ultraviolet region. These promising LOG materials are transparent to visible rays, and thus have potential applications. C1 Hubei Univ, Dept Phys, Wuhan 430062, Peoples R China. Emory Univ, Cherry L Emerson Ctr Sci Computat, Atlanta, GA 30322 USA. Emory Univ, Dept Chem, Atlanta, GA 30322 USA. Dalian Univ Technol, Coll Adv Sci & Technol, Dalian 116024, Peoples R China. Dalian Univ Technol, State Key Lab Mat Modificat Laser Electron & Ion, Dalian 116024, Peoples R China. NCI, Med Chem Lab, CCR, NIH,DHHS, Frederick, MD 21702 USA. Univ Szczecin, Inst Phys, PL-70451 Szczecin, Poland. RP Xie, JRH (reprint author), Hubei Univ, Dept Phys, Wuhan 430062, Peoples R China. NR 37 TC 6 Z9 6 U1 0 U2 4 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1546-1955 EI 1546-1963 J9 J COMPUT THEOR NANOS JI J. Comput. Theor. Nanosci. PD JAN PY 2007 VL 4 IS 1 BP 142 EP 146 PG 5 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 143NW UT WOS:000244730300014 ER PT J AU Wada, D Lim, M Harris, R Velasco, C Jaffe, E AF Wada, D. Lim, M. Harris, R. Velasco, C. Jaffe, E. TI Solitary CD30+ lymphoproliferative lesion of the tongue: An unusual manifestation of lymphomatoid papulosis? SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. Univ Tennessee, Med Ctr, Knoxville, TN USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2007 VL 34 IS 1 BP 102 EP 102 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 122NL UT WOS:000243233600112 ER PT J AU Sepehr, A Kamangar, F Flotte, T AF Sepehr, A. Kamangar, F. Flotte, T. TI Distinct age-associated morphological variation in pilomatricoma SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2007 VL 34 IS 1 BP 122 EP 122 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 122NL UT WOS:000243233600198 ER PT J AU Connor, EE Meyer, MJ Li, RW Van Amburgh, ME Boisclair, YR Capuco, AV AF Connor, E. E. Meyer, M. J. Li, R. W. Van Amburgh, M. E. Boisclair, Y. R. Capuco, A. V. TI Regulation of gene expression in the bovine mammary gland by ovarian steroids SO JOURNAL OF DAIRY SCIENCE LA English DT Article; Proceedings Paper CT 2006 ADSA/ASAS Joint Annual Meeting CY JUL 09-13, 2006 CL Minneapolis, MN DE gene expression; mammary gland; ovarian steroid ID ESTROGEN-RECEPTOR-ALPHA; PROGESTERONE-RECEPTOR; ER-BETA; BREAST-CANCER; FAT PAD; TRANSCRIPTIONAL ACTIVITY; QUANTITATIVE-ANALYSIS; CELL-PROLIFERATION; RESPONSIVE GENES; EPITHELIAL-CELLS AB It is well established that estrogen is required for mammary epithelial cell proliferation and ductal development in the growing animal, and that lobuloalveolar development during gestation is dependent on progesterone. The effects of these steroid hormones on gene expression in the mammary gland are mediated primarily by their respective nuclear hormone receptors, which function as hormone-bound transcription factors. To gain insight into how estrogen and progesterone regulate mammary gland growth and function in cattle, we and others have characterized the expression patterns of their cognate nuclear hormone receptors in the bovine mammary gland throughout development, pregnancy, and lactation. This work has identified a lack of expression of estrogen receptor beta and a greater abundance of progesterone receptor during lactation in the bovine mammary gland, compared with the rodent gland. We speculate that interactions among the estrogen receptor isoforms that regulate progesterone receptor expression may contribute to these species differences. Further, demonstrated expression of substantial quantities of estrogen receptor within the prepubertal bovine mammary fat pad, along with coordinated insulin-like growth factor-I expression, suggests that this tissue may stimulate parenchymal growth via an estrogen-responsive paracrine mechanism. In addition, the recent availability of bovine genomic sequence information and microarray technologies has permitted the study of global gene expression in the mammary gland in response to the steroid environment. We have identified more than 100 estrogen-responsive genes, of which the majority are novel estrogen gene targets. Estrogen-induced changes in gene expression were consistent with increased mammary epithelial cell proliferation, increased extracellular matrix turnover in parenchyma, and increased extracellular matrix deposition in the fat pad. A comparison of estrogen-responsive genes in the mammary glands of humans, mice, and cattle suggests considerable variation among species, as well as potential differences in regulatory elements in common estrogen receptor gene targets. Continuing studies using advanced molecular techniques should assist in elucidating the complex regulation of mammary function at the transcript level. C1 USDA ARS, Bovine Funct Genom Lab, Beltsville, MD 20705 USA. NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. RP Connor, EE (reprint author), USDA ARS, Bovine Funct Genom Lab, Beltsville, MD 20705 USA. EM econnor@anri.barc.usda.gov NR 71 TC 28 Z9 28 U1 0 U2 6 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PY 2007 VL 90 SU S BP E55 EP E65 DI 10.3168/jds.2006-466 PG 11 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 169PA UT WOS:000246602900004 PM 17517752 ER PT J AU Semioshkina, N Proehl, G Savinkov, A Voigt, G AF Semioshkina, N. Proehl, G. Savinkov, A. Voigt, G. TI The transfer of Cs-137 and Sr-90 from feed to rabbits SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY LA English DT Article DE rabbits; Cs-137; Sr-90; transfer of radionuclides; transfer coefficient ID RADIONUCLIDES; BIOKINETICS; STRONTIUM; HUMANS AB Radiological assessment of the impact of nuclear weapons testing on the local population in the Semi-palatinsk Test Site (STS) requires comprehensive site-specific information on radionuclide behaviour in the environment. However, information on radionuclide behaviour in the conditions of the STS is rather sparse and, in particular, there are no data in the literature on parameters of radionuclide transfer from feed to rabbit products which have been identified as contributors to internal dose to the inhabitants. The transfer of Cs-137 and Sr-90 to rabbit meat was studied under laboratory conditions in a controlled experiment with 32 locally bred rabbits maintained in the Kazakh Agricultural Research Institute. The equilibrium transfer coefficients for Cs-137 and Sr-90 from feed to rabbit meat were estimated to be 0.4 d kg(-1) and 0.15 d kg(-1), respectively. The biological half-lives were estimated to be 0.1 d for Cs-137 and 0.14 d for Sr-90. Whereas for Cs-137 the distribution in the body is relatively homogeneous, there are large differences between the organs and tissues for Sr-90 for which, as expected, the highest concentrations were found in bone. (c) 2007 Elsevier Ltd. All rights reserved. C1 GSF Inst Strahlenschutz, D-85788 Neuherberg, Germany. Minist Sci & Higher Educ Republ Kazakhstan SRAI, Natl Biotechnol Ctr, Sci Res Agr Inst, Gvardeiski 480544, Kazakhstan. IAEA, Seibersdorf, Agcy Labs, A-1400 Vienna, Austria. RP Semioshkina, N (reprint author), GSF Inst Strahlenschutz, Ingolstaedter Landstr 1,Postfach 1129, D-85788 Neuherberg, Germany. EM semi@gsf.de OI Semioshkina, Natalia/0000-0002-8954-5597 NR 14 TC 4 Z9 4 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0265-931X J9 J ENVIRON RADIOACTIV JI J. Environ. Radioact. PY 2007 VL 98 IS 1-2 BP 166 EP 176 DI 10.1016/j.jenvrad.2007.02.012 PG 11 WC Environmental Sciences SC Environmental Sciences & Ecology GA 238GN UT WOS:000251435500011 PM 17761361 ER PT J AU Chan, PC Xia, QS Fu, PP AF Chan, Po-Chuen Xia, Qingsu Fu, Peter P. TI Ginkgo biloba leave extract: Biological, medicinal, and toxicological effects SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Gingko biloba leave extract; biological and toxicological effects; ginkgolidc; quercetin ID HERB-DRUG INTERACTIONS; INDUCED NEURONAL DEATH; GLOBAL BRAIN ISCHEMIA; EGB 761 PROTECTS; DNA-DAMAGE; INDUCED NEPHROTOXICITY; INDUCED TOXICITY; NITRIC-OXIDE; IN-VITRO; CYTOCHROME-P450 PHENOTYPES AB Ginkgo biloba leave extract is among the most widely sold herbal dietary supplements in the United States. Its purported biological effects include: scavenging free radical; lowering oxidative stress; reducing neural damages, reducing platelets aggregation; anti-inflammation; anti-tumor activities; and anti-aging. Clinically, it has been prescribed to treat CNS disorders such as Alzheimer's disease and cognitive deficits. It exerts allergy and changes in bleeding time. While its mutagenicity or carcinogenic activity has not been reported, its components, quercetin, kaempferol and rutin have been shown to be genotoxic. There are no standards or guidelines regulating the constituent components of Ginkgo biloba leave extract nor are exposure limits imposed. Safety evaluation of Ginkgo biloba leave extract is being conducted by the U.S. National Toxicology Program. C1 [Chan, Po-Chuen] NIEHS, Res Triangle Pk, NC 27709 USA. [Xia, Qingsu; Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chan, PC (reprint author), NIEHS, Res Triangle Pk, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov NR 161 TC 114 Z9 124 U1 3 U2 49 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2007 VL 25 IS 3 BP 211 EP 244 DI 10.1080/10590500701569414 PG 34 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 264DD UT WOS:000253264800002 PM 17763047 ER PT J AU Crane, NJ Bartick, EG Perlman, RS Huffman, S AF Crane, Nicole J. Bartick, Edward G. Perlman, Rebecca Schwartz Huffman, Scott TI Infrared spectroscopic imaging for noninvasive detection of latent fingerprints SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; latent fingerprints; FTIR; spectroscopic imaging; trace evidence ID VISIBLE ABSORPTION; BONE; MICROSPECTROSCOPY; LUMINESCENCE; ENHANCEMENT; COLLAGEN; SYSTEM; TISSUE AB The capability of Fourier transform infrared (FTIR) spectroscopic imaging to provide detailed images of unprocessed latent fingerprints while also preserving important trace evidence is demonstrated. Unprocessed fingerprints were developed on various porous and nonporous substrates. Data-processing methods used to extract the latent fingerprint ridge pattern from the background material included basic infrared spectroscopic band intensities, addition and subtraction of band intensity measurements, principal components analysis (PCA) and calculation of second derivative band intensities, as well as combinations of these various techniques. Additionally, trace evidence within the fingerprints was recovered and identified. C1 Fed Bur Invest Acad, Counterterrorism & Forens Sci Res Unit, FBI Lab, Oak Ridge Inst Sci Educ, Quantico, VA 22135 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bartick, EG (reprint author), Suffolk Univ, Dept Chem & Biochem, 41 Temple St, Boston, MA 02114 USA. EM ebartick@suffolk.edu FU Intramural NIH HHS NR 34 TC 76 Z9 82 U1 5 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JAN PY 2007 VL 52 IS 1 BP 48 EP 53 DI 10.1111/j.1556-4029.2006.00330.x PG 6 WC Medicine, Legal SC Legal Medicine GA 119EA UT WOS:000242993800009 PM 17209909 ER PT J AU Haas, JS Miglioretti, DL Geller, B Buist, DSM Nelson, DE Kerlikowske, K Carney, PA Dash, S Breslau, ES Ballard-Barbash, R AF Haas, Jennifer S. Miglioretti, Diana L. Geller, Berta Buist, Diana S. M. Nelson, David E. Kerlikowske, Karla Carney, Patricia A. Dash, Sarah Breslau, Erica S. Ballard-Barbash, Rachel TI Average household exposure to newspaper coverage about the harmful effects of hormone therapy and population-based declines in hormone therapy use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE newspaper coverage; women; mammography; hormone therapy; health behavior ID BREAST-CANCER; MASS-MEDIA; REPLACEMENT THERAPY; WOMEN; RELEASE; MODELS; TRIAL; NEWS AB BACKGROUND: The news media facilitated the rapid dissemination of the findings from the estrogen plus progestin therapy arm of the Women's Health Initiative (EPT-WHI). OBJECTIVE: To examine the relationship between the potential exposure to newspaper coverage and subsequent hormone therapy (HT) use. DESIGN/POPULATION: Population-based cohort of women receiving mammography at 7 sites (327,144 postmenopausal women). MEASUREMENTS: The outcome was the monthly prevalence of self-reported HT use. Circulation data for local, regional, and national newspapers was used to create zip-code level measures of the estimated average household exposure to newspaper coverage that reported the harmful effects of HT in July 2002. RESULTS: Women had an average potential household exposure of 1.4 articles. There was substantial variation in the level of average household exposure to newspaper coverage; women from rural sites received less than women from urban sites. Use of HT declined for all average potential exposure groups after the publication of the EPT-WHI. HT prevalence among women who lived in areas where there was an average household exposure of at least 3 articles declined significantly more (45 to 27%) compared to women who lived in areas with < 1 article (43 to 31%) during each of the subsequent 5 months ( relative risks 0.86-0.92; p <. 006 for all). CONCLUSIONS: Greater average household exposure to newspaper coverage about the harms associated with HT was associated with a large population-based decline in HT use. Further studies should examine whether media coverage directly influences the health behavior of individual women. C1 Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Boston, MA 02120 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Vermont, Off Hlth Promot Res, Dept Family Med, Vermont Canc Ctr, Burlington, VT USA. Univ Vermont, Off Hlth Promot Res, Dept Radiol, Vermont Canc Ctr, Burlington, VT USA. Ctr Dis Control & Prevent, Hlth Commun Branch, Off Smoking & Hlth, Atlanta, GA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94143 USA. Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. NCI, Appl Res Program, Div Canc Control & Populat Studies, Bethesda, MD 20892 USA. NCI, Behav Res Program, Div Canc Control & Populat Studies, Bethesda, MD 20892 USA. RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jhaas@partners.org FU NCI NIH HHS [U01 CA086076-06, U01 CA063731, U01 CA063740, U01 CA086082, U01CA63731, U01CA63740, U01CA86082, U01 CA070013, R01 CA080888, U01 CA063736, U01 CA069976, U01 CA070040, U01 CA086076, U01CA63736, U01CA69976, U01CA70013, U01CA70040, U01CA86076] NR 31 TC 14 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2007 VL 22 IS 1 BP 68 EP 73 DI 10.1007/s11606-007-0122-7 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 140QW UT WOS:000244521800009 PM 17351842 ER PT J AU Moser, RP McCaul, K Peters, E Nelson, W Marcus, SE AF Moser, Richard P. McCaul, Kevin Peters, Ellen Nelson, Wendy Marcus, Stephen E. TI Associations of perceived risk and worry with cancer health-protective actions - Data from the Health Information National Trends Survey (HINTS) SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE behavioral sciences; health promotion; risk ID COLORECTAL-CANCER; SCREENING PRACTICES; REPEAT MAMMOGRAPHY; INTERVIEW SURVEY; BREAST; PROSTATE; BEHAVIOR; PERCEPTIONS; BELIEFS; CONSEQUENCES AB This study examined the associations of susceptibility, conceptualized as both a cognition (risk) and as affect (worry) and their possible interaction, with cancer screening behaviors. Data for this study were obtained from the 2003 Health Information National Trends Survey (HINTS). Hierarchical regression models assessed the ability of risk, worry and their interaction (after controlling for other important variables) to predict cancer-screening behaviors. Results found that risk and worry (but not their interaction) were associated with regular mammography screening and having had a sigmoidoscopy or colonoscopy but with neither FOBT nor PSA screening. The findings suggest that risk and worry are both important in predicting some types of screening behavior and that these variables operate independently. C1 NCI, Bethesda, MD 20892 USA. Univ Oregon, Eugene, OR 97403 USA. RP Moser, RP (reprint author), NCI, 6130 Execut Blvd,MSC 7326,Room 4052, Bethesda, MD 20892 USA. EM moserr@mail.nih.gov NR 35 TC 58 Z9 58 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD JAN PY 2007 VL 12 IS 1 BP 53 EP 65 DI 10.1177/1359105307071735 PG 13 WC Psychology, Clinical SC Psychology GA 128WB UT WOS:000243689300005 PM 17158840 ER PT J AU Gottwein, JM Scheel, TK Eugen-Olsen, J Bukh, J AF Gottwein, J. M. Scheel, T. K. Eugen-Olsen, J. Bukh, J. TI Novel chimeric cell culture systems for hepatitis C genotypes 1A, 1B, 3A and 4A SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 42th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 11-15, 2007 CL Barcelona, SPAIN SP European Assoc Study Liver C1 Copenhagen Univ Hosp, Dept Infect Dis, Clin Res Unit, Hvidovre, Denmark. Univ Copenhagen, Panum Inst, Inst Microbiol & Immunol, DK-2200 Copenhagen, Denmark. NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. EM judith@gottwein.cu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2007 VL 46 SU 1 MA 65 BP S30 EP S30 DI 10.1016/S0168-8278(07)61663-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 168WQ UT WOS:000246555100066 ER PT J AU Siegmund, SV Qian, T de Minicis, S Harvey-White, J Kunos, G Vinod, KY Hungund, B Brenner, DA Schwabe, RF AF Siegmund, S. V. Qian, T. de Minicis, S. Harvey-White, J. Kunos, G. Vinod, K. Y. Hungund, B. Brenner, D. A. Schwabe, R. F. TI The endocannabinoid 2-arachidonoyl glycerol induces apoptosis in primary hepatic stellate cells via membrane cholesterol and mitochondrial ros production independently of cannabinoid-receptors or nadph oxidase activation SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 42th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 11-15, 2007 CL Barcelona, SPAIN SP European Assoc Study Liver C1 Univ Heidelberg, Univ Hosp Mannheim, Dept Med Gastroenterol & Hepatol 2, D-6800 Mannheim, Germany. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Univ Texas, Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77550 USA. NIAAA, NIH, Bethesda, MD USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. EM soeren.siegmund@med.ma.uni-heidelberg.de NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2007 VL 46 SU 1 MA 339 BP S133 EP S133 DI 10.1016/S0168-8278(07)61937-0 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 168WQ UT WOS:000246555100339 ER PT J AU Giger, U Hannah, S Ostrander, EA AF Giger, Urs Hannah, Steven Ostrander, Elaine A. TI Symposium issue: Third International Conference - Advances in canine and feline genomics School of Veterinary Medicine, University of California, Davis, CA, August 3-5, 2006 SO JOURNAL OF HEREDITY LA English DT Editorial Material C1 Univ Penn, Philadelphia, PA 19104 USA. Nestle Purina PetCare, St Louis, MO USA. NIH, Bethesda, MD 20892 USA. RP Giger, U (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 3 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 0022-1503 EI 1465-7333 J9 J HERED JI J. Hered. PY 2007 VL 98 IS 5 SI SI BP 385 EP 385 DI 10.1093/jhered/esm076 PG 1 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 213IJ UT WOS:000249659800001 ER PT J AU Pontius, JU O'Brien, SJ AF Pontius, Joan U. O'Brien, Stephen J. TI Genome annotation resource Fields-GARFIELD: A genome browser for Felis catus SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT 3rd International Conference on Advances in Canine and Feline Genomics CY AUG 03-05, 2006 CL Univ California, Sch Vet Med, Davis, CA HO Univ California, Sch Vet Med ID DATABASE AB Annotation features from the 1.9-fold whole-genome shotgun (WGS) sequences of domestic cat have been organized into an interactive web application, Genome Annotation Resource Fields (GARFIELD) (http://lgd.abcc.ncifcrf.gov) at the Laboratory of Genomic Diversity and Advanced Biomedical Computing Center (ABCC) at The National Cancer Institute (NCI). The GARFIELD browser allows the user to view annotations on a per chromosome basis with unplaced contigs provided on placeholder chromosomes. Various tracks on the browser allow display of annotations. A Genes track on the browser includes 20 285 regions that align to genes annotated in other mammalian genomes: Homo sapiens, Pan troglodytes, Mus musculus, Rattus norvegicus, Bos taurus, and Canis familiaris. Also available are tracks that display the contigs that make up the chromosomes and representations of their GC content and repetitive elements as detected using the RepeatMasker (http://www.repeatmasker.org). Data from the browser can be downloaded in FASTA and GFF format, and users can upload their own data to the display. The Felis catus sequences and their chromosome assignments and additional annotations incorporate data analyzed and produced by a multicenter collaboration between NCI, ABCC, Agencourt Biosciences Corporation, Broad Institute of Harvard and Massachusetts Institute of Technology, National Human Genome Research Institute, National Center for Biotechnology and Information, and Texas A&M. C1 SAIC Frederick Inc, NCI Frederick, Lab Genome Divers, Frederick, MD 21702 USA. RP Pontius, JU (reprint author), SAIC Frederick Inc, NCI Frederick, Lab Genome Divers, Frederick, MD 21702 USA. EM pontiusj@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 6 TC 27 Z9 27 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PY 2007 VL 98 IS 5 SI SI BP 386 EP 389 DI 10.1093/jhered/esm055 PG 4 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 213IJ UT WOS:000249659800002 PM 17646276 ER PT J AU Yuhki, N Beck, T Stephens, R Neelam, B O'Brien, SJ AF Yuhki, Naoya Beck, Thomas Stephens, Robert Neelam, Beena O'Brien, Stephen J. TI Comparative genomic structure of human, dog, and cat MHC: HLA, DLA, and FLA SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT 3rd International Conference on Advances in Canine and Feline Genomics CY AUG 03-05, 2006 CL Univ California, Sch Vet Med, Davis, CA HO Univ California, Sch Vet Med ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II REGION; ANTIGEN-BINDING SITE; SEQUENCE-ANALYSIS; DNA-SEQUENCES; ORGANIZATION; MOLECULES; GENES; MAP; DIVERGENCE AB Comparisons of the genomic structure of 3 mammalian major histocompatibility complexes (MHCs), human HLA, canine DLA, and feline FLA revealed remarkable structural differences between HLA and the other 2 MHCs. The 4.6-Mb HLA sequence was compared with the 3.9-Mb DLA sequence from 2 supercontigs generated by 7x whole-genome shotgun assembly and 3.3-Mb FLA draft sequence. For FLA, we confirm that 1) feline FLA was split into 2 pieces within the TRIM (member of the tripartite motif) gene family found in human HI-A, 2) class 11, 111, and I regions were placed in the peri-centromeric region of the long arm of chromosome B2, and 3) the remaining FLA was located in subtelomeric region of the short arm of chromosome B2. The exact same chromosome break was found in canine DLA structure, where class 11, 111, and 1 regions were placed in a pericentromeric region of chromosome 12 whereas the remaining region was located in a subtelomeric region of chromosome 35, suggesting that this chromosome break occurred once before the split of felid and canid more than 55 million years ago. However, significant differences were found in the content of genes in both pericentromeric and subtelomeric regions in DLA and FLA, the gene number, and amplicon structure of class I genes plus 2 other class I genes found on 2 additional chromosomes; canine chromosomes 7 and 18 suggest the dynamic nature in the evolution of MHC class I genes. C1 NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA. NCI, SAIC Frederick, Ft Detrick, MD 21702 USA. NCI, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA. RP Yuhki, N (reprint author), NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA. EM yuhki@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 51 TC 29 Z9 30 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PY 2007 VL 98 IS 5 SI SI BP 390 EP 399 DI 10.1093/jhered/esm056 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 213IJ UT WOS:000249659800003 PM 17675392 ER PT J AU Luo, SJ Johnson, WF David, VA Menotti-Raymond, M Stanyon, R Cai, QX Beck, T Yuhki, N Pecon-Slattery, J Smith, JLD O'Brien, SJ AF Luo, Shu-Jin Johnson, Warren F. David, Victor A. Menotti-Raymond, Marilyn Stanyon, Roscoe Cai, Qing Xiu Beck, Thomas Yuhki, Nacya Pecon-Slattery, Jill Smith, James L. D. O'Brien, Stephen J. TI Development of Y chromosome intraspecific polymorphic markers in the Felidae SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT 3rd International Conference on Advances in Canine and Feline Genomics CY AUG 03-05, 2006 CL Univ California, Sch Vet Med, Davis, CA HO Univ California, Sch Vet Med ID SHREW CROCIDURA-RUSSULA; CLASS-II REGION; DOMESTIC CAT; MICROSATELLITE MARKERS; EVOLUTIONARY HISTORY; DNA LIBRARIES; GENOMIC DNA; RADIATION; MOUSE; SEQUENCES AB Y chromosome haplotyping based on microsatetlites and single nucleoticle polymorphisms (SNPs) has proved to be a powerful tool for population genetic studies of humans. However, the promise of the approach is hampered in the majority of nonhuman mammals by the lack of Y-specific polymorphic markers. We were able to identify new male-specific polymorphisms in the domestic cat Felix catus and 6 additional Felidae species with a combination of molecular genetic and cytogenetic approaches including 1) identifying domestic cat male-specific microsatellites from markers generated from a male cat microsatellite-enriched genomic library, a flow-sorted Y cosmid library, or a Y-specific cat bacteria artificial chromosome (BAC) clone, (2) constructing microsatellite-enriched libraries from flow-sorted Y chromosomes isolated directly from focal wildcat species, and (3) screening Y chromosome conserved anchored tagged sequences primers in Felidae species. Forty-one male-specific microsatellites were identified, but only 6 were single-copy loci, consistent with the repetitive nature of the Y chromosome. Nucleotide diversity (pi) of Y-linked intron sequences (2.1 kbp) was in the range of 0 (tiger) to 9.95 x 10(-4) (marbled cat), and the number of SNPs ranged from none in the tiger to 7 in the Asian leopard cat.. ping system described here, consisting of 4 introns (SMCY3, SMCY7, UTY11, and DBY7) and 1 polymorphic The Y haploty microsatellite (SMCY-STR), represents the first available markers for tracking intraspecific male lineage polymorphisms in Felidae species and promises to provide significant insights to evolutionary and population genetic studies of the species. C1 NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA. Univ Minnesota, Dept Fisheries Wildlife & Conservat Biol, St Paul, MN 55108 USA. Univ Florence, Dept Anim Biol & Genet, Florence, Italy. Beijing Normal Univ, Minist Educ, Inst Ecol, Key Lab Biodivers Sci & Ecol Engn, Beijing 100875, Peoples R China. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA. EM luos@ncifcrf.gov RI Johnson, Warren/D-4149-2016; OI Johnson, Warren/0000-0002-5954-186X; Stanyon, Roscoe/0000-0002-7229-1092 FU NCI NIH HHS [N01-CO-12400] NR 60 TC 20 Z9 20 U1 0 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 EI 1465-7333 J9 J HERED JI J. Hered. PY 2007 VL 98 IS 5 SI SI BP 400 EP 413 DI 10.1093/jhered/esm063 PG 14 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 213IJ UT WOS:000249659800004 PM 17646273 ER PT J AU Antunes, A Pontius, J Ramos, MJ O'Brien, SJ Johnson, WE AF Antunes, Agostinho Pontius, Joan Ramos, Maria Joao O'Brien, Stephen J. Johnson, Warren E. TI Mitochondrial introgressions into the nuclear genome of the domestic cat SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT 3rd International Conference on Advances in Canine and Feline Genomics CY AUG 03-05, 2006 CL Univ California, Sch Vet Med, Davis, CA HO Univ California, Sch Vet Med ID DNA; PSEUDOGENES; MTDNA; SEQUENCES; GENE; NUMT; INSERTIONS; EVOLUTION; DUPLICATIONS; INTEGRATIONS AB Translocation of mtDNA into the nuclear genome, also referred to as numt, was first reported in the domestic cat (Felis catus) by Lopez et al. (1994). The Lopez-numt consisted of a translocation of 7.9 kbp of mtDNA that inserted into the domestic cat chromosome D2 around 1.8 million years ago. More than a decade later, the release of the domestic cat whole-genome shotgun sequences (1.9 X coverage) provides the resource to obtain more comprehensive insight into the extent of mtDNA transfer over time in the domestic cat genome. MegaBLAST searches revealed that the cat genome harbors a wide variety of numts (298 320 bp), one-third of which likely correspond to the Lopez-numt tandem repeat, whereas the remaining numts are probably derived from multiple independent insertions, which in some cases were followed by segmental duplication after insertion in the nucleus. Numts were detected across most cat chromosomes, but the number of numts assigned to chromosomes is underestimated due to the relatively high number of numt sequences with insufficient flanking sequence to map. The catalog of cat numts provides a valuable resource for future studies in Felidae species, including its use as a tool to avoid numt contaminations that may confound population generics and phylogenetic studies. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. Univ Porto, REQUIMTE, Dept Quim, Fac Ciencias, P-4169007 Oporto, Portugal. Univ Porto, CIMAR, Ctr Interdisciplinar Invest Marinha & Ambiental, P-4050123 Oporto, Portugal. SAIC Frederick Inc, Basic Res Program, Lab Genom Divers, Ft Detrick, MD 21702 USA. RP Johnson, WE (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. EM johnsonw@ncifcrf.gov RI REQUIMTE, AL/H-9106-2013; REQUIMTE, TCB/M-6190-2013; REQUIMTE, UCIBIO/N-9846-2013; Scientific output, CIIMAR/E-5122-2012; Ramos, Maria/D-6183-2013; Johnson, Warren/D-4149-2016; OI Scientific output, CIIMAR/0000-0001-6270-2153; Ramos, Maria/0000-0002-7554-8324; Johnson, Warren/0000-0002-5954-186X; Antunes, Agostinho/0000-0002-1328-1732 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 36 TC 16 Z9 19 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PY 2007 VL 98 IS 5 SI SI BP 414 EP 420 DI 10.1093/jhered/esm062 PG 7 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 213IJ UT WOS:000249659800005 PM 17660503 ER PT J AU Trinchieri, G AF Trinchieri, Giorgio TI The birth of a cell type SO JOURNAL OF IMMUNOLOGY LA English DT Editorial Material ID PERIPHERAL LYMPHOID ORGANS; FOLLICULAR DENDRITIC CELLS; COLONY-STIMULATING FACTOR; MOUSE SPLEEN; IN-VITRO; MICE; IDENTIFICATION; MACROPHAGE; ANTIGEN; GENERATION C1 NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM trinchig@mail.nih.gov NR 21 TC 1 Z9 1 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 JAN 1 PY 2007 VL 178 IS 1 BP 3 EP 4 PG 2 WC Immunology SC Immunology GA 120XU UT WOS:000243120900001 PM 17182534 ER PT J AU Thananchai, H Gillespie, G Martin, MP Bashirova, A Yawata, N Yawata, M Easterbrook, P McVicar, DW Maenaka, K Parham, P Carrington, M Dong, T Rowland-Jones, S AF Thananchai, Hathairat Gillespie, Geraldine Martin, Maureen P. Bashirova, Arman Yawata, Nobuyo Yawata, Makoto Easterbrook, Philippa McVicar, Daniel W. Maenaka, Katsumi Parham, Peter Carrington, Mary Dong, Tao Rowland-Jones, Sarah TI Cutting edge: Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-LIKE RECEPTORS; CELL INHIBITORY RECEPTORS; NATURAL-KILLER-CELLS; POLYMORPHISMS; RECOGNITION; KIR; DIVERSIFICATION; PROGRESSION; COMPLEXES; SELECTION AB Although it is clear that KIR3DL1 recognizes Bw4(+) HLA-B, the role of Bw4(+) HLA-A allotypes as KIR3DL1 ligands is controversial We therefore examined the hinding of tetrameric HLA-A and -B complexes, including HLA*2402, a common Bw4(+) HLA-A allotype, to KIR3DLI*001, *005, *007, and *1502 allotypes. Only Bw4(+) tetramers hound K7R3DL1. Three of four HLA-A*2402 tetramers bound one or more KIR3DL1 allotypes and all four KIR3DL1 allotypes bound to one or more HLA-A*2402 tetramers, but with different binding specificities. Only KTR3DL1*005 bound both HLA-A*2402 and HLA-B*5703 tetramers. HLA-A*2402-expressing target cells were resistant to lysis by NK cells expressing KIR3DL1*001 or *005. This study shows that HLA-A*2402 is a ligand for KIR3DL1 and demonstrates how the binding of KIR3DL1 to Bw4(+) ligands depends upon the bound peptide as well as HLA and KIR3DL1 polymorphism. C1 MRC, Human Immunol Unit, Weatherall Inst Mol Med, Oxford, England. Sci Applicat Int Corp, Lab Genom Delivery, NCI, Frederick, MD 21702 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. Huys Kings & St Thomas Sch Med, Dept HIV Genitourinary Med, London, England. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. Kyushu Univ, Med Inst Bioregulat, Div Struct Biol, Fukuoka 812, Japan. RP Dong, T (reprint author), John Radcliffe Hosp, MRC, Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DS, England. EM TDong@hammer.imm.ox.ac.uk; sarah.rowland-jones@ndm.ox.ac.uk RI Yawata, Makoto/D-8366-2015; McVicar, Daniel/G-1970-2015 FU Medical Research Council [G0200585, MC_U137884180]; NCI NIH HHS [N01-CO-12400] NR 28 TC 148 Z9 148 U1 0 U2 17 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2007 VL 178 IS 1 BP 33 EP 37 PG 5 WC Immunology SC Immunology GA 120XU UT WOS:000243120900004 PM 17182537 ER PT J AU Jiang, Q Huang, J Li, WQ Cavinato, T Keller, JR Durum, SK AF Jiang, Qiong Huang, Jiaqiang Li, Wen Qing Cavinato, Tiziana Keller, Jonathan R. Durum, Scott K. TI Role of the intracellular domain of IL-7 receptor in T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; THYMIC LYMPHOMAS; PHOSPHATIDYLINOSITOL 3-KINASE; DISTINCT ROLES; CYTOKINE; STAT5; GENE; DIFFERENTIATION; PROLIFERATION AB Signals from the IL-7R are uniquely required for T cell development and maintenance, despite the resemblance of IL-7R to other cytokine receptors and the apparent sharing of common signaling pathways. This unique requirement could either reflect unique expression of IL-7R or IL-7R or it could indicate that the IL-7R delivers unique signals. To determine whether the IL-7R provided unique signals, we exchanged its intracellular domain with that of other cytokine receptors: IL-4R, IL-9R, and prolactin receptor (PRLR). Chimeric receptors were used to reconstitute development of IL-7R(-/-) hemopoietic progenitors by transducing the receptors in retroviral vectors. Whereas.IL-7R(-/-) thymocytes are arrested at the double-negative stage, IL-4R, IL-9R, or PRLR all imparted some progression to the double-positive stage. IL-4R and PRLR gave only small numbers of thymocytes, whereas IL-9R gave robust alpha beta T cell development and reconstitution of peripheral CD4 and CD8 cells, indicating that it can duplicate many of the functions of IL-7r. However, IL-9R failed to reconstitute rearrangement of the TCR gamma locus or development of gamma delta T cells. Thus, the IL-7R signals required in the alpha beta T cell lineage (such as survival and proliferation) are not unique to this receptor, whereas rearrangement of the TCR gamma locus may require a signal that is not shared by other receptors. C1 NCI, Lab Mol Immunoregulat, Ctr Canc Res, Frederick, MD 21702 USA. Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21231 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21701 USA. RP Durum, SK (reprint author), Sect Cytokines & Immun, Bldg 560,Room 31-71, Frederick, MD 21702 USA. EM durums@mail.ncifcrf.gov FU Intramural NIH HHS NR 44 TC 4 Z9 5 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2007 VL 178 IS 1 BP 228 EP 234 PG 7 WC Immunology SC Immunology GA 120XU UT WOS:000243120900026 PM 17182559 ER PT J AU Ghochikyan, A Mkrtichyan, M Loukinov, D Mamikonyan, G Pack, SD Movsesyan, N Ichim, TE Cribbs, BH Lobanenkov, VV Agadjanyan, MG AF Ghochikyan, Anahit Mkrtichyan, Mikayel Loukinov, Dmitri Mamikonyan, Gregory Pack, Svetlana D. Movsesyan, Nina Ichim, Thomas E. Cribbs, Bavid H. Lobanenkov, Victor V. Agadjanyan, Michael G. TI Elicitation of T cell responses to histologically unrelated tumors by immunization with the novel cancer-testis antigen, brother of the regulator of imprinted sites SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; METASTATIC MELANOMA; DNA VACCINATION; IMMUNE-RESPONSE; DENDRITIC CELLS; FACTOR BORIS; B-CELLS; CTCF; BINDING; IMMUNOTHERAPY AB Brother of the regulator of imprinted sites (BORIS) was previously described as a transcription factor for epigenetic reprogramming the expression of which is strictly confined to germ cells of adult testes but is aberrantly activated in the vast majority of neoplastic cells. Considering the critical role of BORIS in cancerogenesis and the fact that its expression pattern may preclude thymic tolerance, we generated DNA- and protein-based mouse BORIS antitumor vaccines using a non-DNA-binding version of the BORIS molecule. Clinical use of BORIS as a vaccine Ag would require that certain safety concerns be met. Specifically, administration of the functional BORIS protein would hypothetically pose a risk of BORIS accelerating the progression of cancer. To alleviate such safety concerns, we have developed vaccines based on the BORIS molecule lacking the DNA-binding zinc fingers domain. To enhance anti-BORIS cellular immune responses, we used a standard molecular adjuvant approach. It consisted of plasmids encoding murine IL-12 and IL-18 for a DNA-based vaccine and conventional Th1 type adjuvant, Quil A, for a protein-based vaccine. Both DNA- and protein-based vaccines induced Ag-specific CD4(+) T cell proliferation with Th1 and Th2 cytokine profiles, respectively. Protein-based, but not DNA-based, BORIS vaccine induced a significant level of Ab production in immunized animals. Importantly, potent anticancer CD8(+)-cytotoxic lymphocytes were generated after immunization with the DNA-based, but not protein-based, BORIS vaccine. These cytolytic responses were observed across a wide range of different mouse cancers including mammary adenocarcinoma, glioma, leukemia, and mastocytoma. C1 Inst Mol Med, Dept Mol Immunol, Huntington Beach, CA 92647 USA. Univ Calif Irvine, Inst Brain Aging & Demtia, Dept Neurol, Irvine, CA 92697 USA. OncoMune Inc, Miami, FL 33122 USA. NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. RP Agadjanyan, MG (reprint author), Inst Mol Med, Dept Mol Immunol, 16371 Gothard St, Huntington Beach, CA 92647 USA. EM magadjanyan@immed.org RI Pack, Svetlana/C-2020-2014 FU NIA NIH HHS [R01 AG020241, R01 AG-20241, R01 AG020241-06]; NIAID NIH HHS [R01 AI-44809, R01 AI044809-06, R01 AI044809]; NINDS NIH HHS [R01 NS-050895, R01 NS050895, R01 NS050895-04] NR 59 TC 19 Z9 20 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 JAN 1 PY 2007 VL 178 IS 1 BP 566 EP 573 PG 8 WC Immunology SC Immunology GA 120XU UT WOS:000243120900064 PM 17182597 ER PT J AU Shen, XL Zhou, JH Hathcock, KS Robbins, P Powell, DJ Rosenberg, SA Hodes, RJ AF Shen, Xinglei Zhou, Juhua Hathcock, Karen S. Robbins, Paul Powell, Daniel J., Jr. Rosenberg, Steven A. Hodes, Richard J. TI Persistence of tumor infiltrating lymphocytes in adoptive immunotherapy correlates with telomere length SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cancer; immunotherapy; telomere; telomerase ID CD8(+) T-CELLS; TRANSFER THERAPY; LIFE-SPAN; IN-VIVO; REPLICATIVE SENESCENCE; CANCER REGRESSION; MELANOMA PATIENTS; FLOW-CYTOMETRY; ACTIVATION; EXPRESSION AB Transfer of autologous tumor-specific tumor infiltrating lymphocytes (TILs) in adoptive immunotherapy can mediate the regression of tumor in patients with metastatic melanoma. In this procedure, TILs from resected tumors are expanded in vitro, then administered to patients and further stimulated to proliferate in vivo by the administration of high dose IL-2. After in vitro expansion, TILs are often dominated by a few specific clonotypes, and recently it was reported that the persistence in vivo of one or more of these clonotypes correlated with positive therapeutic response. We and others have previously shown that repeated in vitro stimulation and clonal expansion of normal human T lymphocytes results in progressive decrease in telomerase activity and shortening of telomeres, ultimately resulting in replicative senescence. In the studies reported here, we therefore compared telomerase activity and telomere length in persistent and nonpersistent TIL clonotypes before transfer in vivo, and found a correlation between telomere length and clonal persistence. We also observed that TILs proliferate extensively in vivo in the days after transfer, but fail to induce substantial telomerase activity, and undergo rapid decreases in telomere length within days after transfer. Thus, in vivo loss of telomeres by clonotypes that have the shortest telomeres at the time of administration may drive these clones to replicative senescence, whereas cells with longer telomeres are able to persist and mediate antitumor effects. These findings are relevant both to predicting effectiveness of adoptive immunotherapy and in deriving strategies for improving effectiveness by sustaining telomere length. C1 NIH, NIA, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Hodes, RJ (reprint author), NIH, NIA, Bldg 31,Rm 5C35,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Richard_Hodes@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 32 TC 70 Z9 71 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 2007 VL 30 IS 1 BP 123 EP 129 DI 10.1097/01.cji.0000211321.07654.b8 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 120NJ UT WOS:000243091400013 PM 17198091 ER PT J AU Smith, FO Goff, SL Klapper, JA Levy, C Allen, T Mavroukakis, SA Rosenberg, SA AF Smith, Franz O. Goff, Stephanie L. Klapper, Jacob A. Levy, Catherine Allen, Tamika Mavroukakis, Sharon A. Rosenberg, Steven A. TI Risk of bowel perforation in patients receiving interleukin-2 after therapy with anti-CTLA 4 monoclonal antibody SO JOURNAL OF IMMUNOTHERAPY LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Smith, FO (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-32] NR 2 TC 27 Z9 28 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 2007 VL 30 IS 1 BP 130 EP 130 DI 10.1097/01.cji.0000211334.06762.89 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 120NJ UT WOS:000243091400014 PM 17198092 ER PT J AU Huegel, R Velasco, P Sierra, MDL Christophers, E Schroder, JM Schwarz, T Tosato, G Lange-Asschenfeldt, B AF Huegel, Rainer Velasco, Paula Sierra, Maria De La Luz Christophers, Enno Schroeder, Jens M. Schwarz, Thomas Tosato, Giovanna Lange-Asschenfeldt, Bernhard TI Novel anti-inflammatory properties of the angiogenesis inhibitor vasostatin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID VASCULAR-PERMEABILITY FACTOR; ENDOTHELIAL GROWTH-FACTOR; TRANSGENIC MICE; TUMOR-GROWTH; DELAYED-HYPERSENSITIVITY; INFLAMMATION; SKIN; CELLS; ANGIOPOIETIN-1; EXPRESSION AB Endothelial cells are critically involved in the pathogenesis of inflammation, which is characterized by vasopermeability, plasma leakage, leukocyte recruitment, and neovascularization. Therefore, inhibitors of endothelial cell function could reduce inflammation. In this study, we evaluated the effects of the angiogenesis inhibitor vasostatin on inflammations induced by contact hypersensitivity reactions in mouse ears. Vasostatin-treated mice revealed significantly reduced edema formation, resulting from lower plasma leakage and inhibition of inflammation-associated vascular remodeling. Intravital microscopy studies of inflamed ears showed a decrease in the fraction of rolling leukocytes in vasostatin-treated mice, and Lycopersicon esculentum lectin-perfused ears revealed fewer leukocytes adherent to the vessel wall. The inflammatory infiltrate from vasostatin-treated mice was characterized by fewer CD8(+) T cells, neutrophils, and macrophages compared to the saline-treated animals. In a modified Miles assay, vasostatin inhibited vascular endothelial growth factor-A-induced permeability, and inflamed ear tissues from vasostatin-treated mice expressed significantly reduced levels of the vascular destabilizer angiopoietin-2. These results reveal a previously unrecognized anti-inflammatory property of the angiogenesis inhibitor vasostatin, and suggest that vasostatin is a potential candidate drug for the treatment of inflammation. C1 Univ Hosp Schleswig Holstein, Dept Dermatol, D-24105 Kiel, Germany. NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lange-Asschenfeldt, B (reprint author), Univ Hosp Schleswig Holstein, Dept Dermatol, Campus Kiel,Schittenhelm Str 7, D-24105 Kiel, Germany. EM blange@dermatology.uni-kiel.de RI Schroeder, Jens/B-3994-2009; Schwarz, Thomas/A-9148-2010 NR 40 TC 17 Z9 17 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2007 VL 127 IS 1 BP 65 EP 74 DI 10.1038/sj.jid.5700484 PG 10 WC Dermatology SC Dermatology GA 121YF UT WOS:000243192200011 PM 16888632 ER PT J AU Dreisbach, AW Japa, S Newman, JW Sigel, A Gill, RS Hess, AE Hammock, BD Letrora, JLL AF Dreisbach, A. W. Japa, S. Newman, J. W. Sigel, A. Gill, R. S. Hess, A. E. Hammock, B. D. Letrora, J. L. L. TI Salt loading increases the urinary excretion of linoleic diols and triols in healthy human subjects. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT 8th Conference of the Western Student Medical Research Forum CY FEB 02, 2007 CL Monterey, CA C1 Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Univ Calif Davis, Davis, CA 95616 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2007 VL 55 IS 1 SU S BP S307 EP S307 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 185DU UT WOS:000247692401355 ER PT J AU Kim, BS Miyagawa, F Cho, YH Bennett, CL Clausen, BE Katz, SJ AF Kim, B. S. Miyagawa, F. Cho, Y.-H. Bennett, C. L. Clausen, B. E. Katz, S. J. TI Keratinocytes induce graft-versus-host disease by presentation of epidermal self-antigen to CD8 T cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT 8th Conference of the Western Student Medical Research Forum CY FEB 02, 2007 CL Monterey, CA C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, HHMI NIH Res Scholars Program, Bethesda, MD 20817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2007 VL 55 IS 1 SU S BP S143 EP S143 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 185DU UT WOS:000247692400420 ER PT J AU Rosenberg, HF Oppenheim, JJ Capogrossi, MC AF Rosenberg, Helene F. Oppenheim, Joost J. Capogrossi, Maurizio C. TI Interview with Dr. Maurizio C. Capogrossi regarding pivotal advance: High-mobility group box 1 protein - a cytokine with a role in cardiac repair SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID STEM-CELLS; INFARCTED MYOCARDIUM; PROLIFERATION; DIFFERENTIATION; REGENERATE; MIGRATION C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21701 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. EM hrosenberg@niaid.oih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2007 VL 81 IS 1 BP 38 EP 40 DI 10.1189/jlb.1306165 PG 3 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 121WN UT WOS:000243187800005 ER PT J AU Yang, D Chen, Q Yang, H Tracey, KJ Bustin, M Oppenheim, JJ AF Yang, De Chen, Qian Yang, Huan Tracey, Kevin J. Bustin, Michael Oppenheim, Joost J. TI High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT EMBO Workshop on Innate Danger Signals and HMGB1 CY FEB 08-11, 2006 CL Milan, ITALY DE RAGE; chemotaxis; maturation; HMGB1 ID GLYCATION END-PRODUCTS; EOSINOPHIL-DERIVED NEUROTOXIN; GROUP CHROMOSOMAL-PROTEINS; NEURITE OUTGROWTH; BINDING PROTEINS; IMMUNE ADJUVANT; NECROTIC CELLS; HMGB1; RECEPTOR; RELEASE AB High mobility group hox-1 (HMGB1) protein is a nonhistone, DNA-binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte-derived, immature DCs (Mo-iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin-inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein-dependent manner. In addition, HMGB1 treatment of Mo-iDCs up-regulated DC surface markers (CD80, CD83, CD86, and HLA-A,B,C), enhanced DC production of cytokines (IL-6, CXCL8, IL-12p70, and TNF alpha), switched DC chemokine responsiveness from CCL5-sensitive to CCL21-sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin. C1 SAIC Frederick Inc, Basic Res Program, NCI, Frederick, MD 21702 USA. Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD USA. N Shore Long Isl Jewish Res Inst, Lab Biomed Sci, Manhasset, NY USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Yang, D (reprint author), SAIC Frederick Inc, Basic Res Program, NCI, Rm 31-19,Bldg 560,1050 Boyles St, Frederick, MD 21702 USA. EM dyang@ncifcrf.gov RI Bustin, Michael/G-6155-2015; OI Tracey, Kevin J/0000-0003-1884-6314 FU NCI NIH HHS [N01-CO-12400]; NIGMS NIH HHS [R01 GM062508] NR 43 TC 236 Z9 260 U1 2 U2 11 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2007 VL 81 IS 1 BP 59 EP 66 DI 10.1189/jlb.0306180 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 121WN UT WOS:000243187800009 PM 16966386 ER PT J AU Watte, CM Nakamura, T Ortaldo, JR Stein-Streilein, JE AF Watte, Christine M. Nakamura, Takahiko Ortaldo, John R. Stein-Streilein, Joan E. TI Ly49C/I co-stimulation induces peripheral tolerance through IL-10 production in NKT cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 11-13, 2007 CL Cambridge, MA SP Soc Leukocyte Biol C1 [Watte, Christine M.; Stein-Streilein, Joan E.] Harvard Med Sch, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. [Nakamura, Takahiko] Kure Med Ctr, Dept Ophthalmol, Kure, Japan. [Ortaldo, John R.] Ctr Canc Res, Natl Canc Inst, Expt Immunol Lab, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2007 SU S MA 10 BP 17 EP 18 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 217LR UT WOS:000249949900011 ER PT J AU de la Rosa, G De Yang Oppenheim, JJ AF de la Rosa, Gonzalo De Yang Oppenheim, Joost J. TI Lactoferrin: A new alarmin? SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 11-13, 2007 CL Cambridge, MA SP Soc Leukocyte Biol C1 [de la Rosa, Gonzalo; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, CIP, Frederick, MD USA. [De Yang] SAIC Frederick, NCI, BRP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2007 SU S MA 22 BP 21 EP 21 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 217LR UT WOS:000249949900023 ER PT J AU McCartney-Francis, N Rekka, S Jin, WW Wahl, SM AF McCartney-Francis, Nancy Rekka, Sofia Jin, Wenwen Wahl, Sharon M. TI Dysregulated expression of IL-17 family members linked to autoimmune-like inflammatory lesions in the absence of TGF-beta 1 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 11-13, 2007 CL Cambridge, MA SP Soc Leukocyte Biol C1 [McCartney-Francis, Nancy; Rekka, Sofia; Jin, Wenwen; Wahl, Sharon M.] NCI, NIDCR, Oral Infect & Immunity Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2007 SU S MA 80 BP 39 EP 39 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 217LR UT WOS:000249949900080 ER PT J AU Greenwell-Wild, T Wen, J Nikitakis, N Moutsopoulos, N Jin, W Ma, G Warburton, G Chaisuparat, R Wahl, SM AF Greenwell-Wild, T. Wen, J. Nikitakis, N. Moutsopoulos, N. Jin, W. Ma, G. Warburton, G. Chaisuparat, R. Wahl, S. M. TI SLPI disrupts plasminogen-dependent proteolysis in inflammation and tumor progression SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 11-13, 2007 CL Cambridge, MA SP Soc Leukocyte Biol C1 [Greenwell-Wild, T.; Wen, J.; Moutsopoulos, N.; Jin, W.; Ma, G.; Wahl, S. M.] NIH, NIDCR, Bethesda, MD USA. [Nikitakis, N.; Warburton, G.; Chaisuparat, R.] Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2007 SU S MA 89 BP 42 EP 42 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 217LR UT WOS:000249949900089 ER PT J AU Moutsopoulos, NM Wen, J Orenstein, J Wahl, SM AF Moutsopoulos, N. M. Wen, J. Orenstein, J. Wahl, S. M. TI Increased TGF-beta in HIV-infected lymphoid tissues may influence Treg accumulation to blunt immune surveillance SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 11-13, 2007 CL Cambridge, MA SP Soc Leukocyte Biol C1 [Moutsopoulos, N. M.; Wen, J.; Wahl, S. M.] NIH, NIDCR, OIIB, Bethesda, MD USA. [Orenstein, J.] George Washington Univ, Washington, DC 20052 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2007 SU S MA 91 BP 43 EP 43 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 217LR UT WOS:000249949900091 ER PT J AU Vazquez, N Wild, T Rekka, S Orenstein, J Wahl, SM AF Vazquez, N. Wild, T. Rekka, S. Orenstein, J. Wahl, S. M. TI M-avium manipulation of host factors supports their persistence in macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 11-13, 2007 CL Cambridge, MA SP Soc Leukocyte Biol C1 [Vazquez, N.; Wild, T.; Rekka, S.; Wahl, S. M.] NIH, NIDCR, Bethesda, MD 20892 USA. [Orenstein, J.] GWU, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2007 SU S MA 152 BP 63 EP 63 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 217LR UT WOS:000249949900152 ER PT J AU Freeman, L Amar, MJA Shamburek, R Paigen, B Brewer, HB Santamarina-Fojo, S Gonzalez-Navarro, H AF Freeman, Lita Amar, Marcelo J. A. Shamburek, Robert Paigen, Beverly Brewer, H. Bryan, Jr. Santamarina-Fojo, Silvia Gonzalez-Navarro, Herminia TI Lipolytic and ligand-binding functions of hepatic lipase protect against atherosclerosis in LDL receptor-deficient mice SO JOURNAL OF LIPID RESEARCH LA English DT Article DE low density lipoprotein receptor; lipase; lipoprotein metabolism; aortic atherosclerosis ID HIGH-DENSITY-LIPOPROTEIN; IN-VIVO EVIDENCE; HUMAN APO-B; TRANSGENIC MICE; APOLIPOPROTEIN-E; PHOSPHOLIPID HYDROLYSIS; PLASMA-LIPOPROTEINS; MEDIATED HYDROLYSIS; TRIGLYCERIDE LIPASE; ENDOTHELIAL LIPASE AB To elucidate the separate contributions of the lipolytic versus ligand-binding functions of hepatic lipase (HL) to lipoprotein metabolism and atherosclerosis, and to investigate the role of the low density lipoprotein receptor (LDLr) in these processes, we compared mice expressing catalytically active HL (HL-WT) with mice expressing inactive HL (HL-S145G) in a background lacking endogenous HL and the LDLr (LDLr-KOXHL-KO). HL-WT and HL-S145G reduced (P < 0.05 for all) cholesterol (55% vs. 20%), non-HDL-cholesterol (63% vs. 22%), and apolipo-protein B (apoB; 34% vs. 16%) by enhancing the catabolism of autologous I-125-apoB-intermediate density lipoprotein (IDL)/LDL (fractional catabolic rate in day(-1): 6.07 +/- 0.25, LDLr-KOXHL-WT; 4.76 +/- 0.30, LDLr-KOXHL-S145G; 3.70 +/- 0.13, LDLr-KOXHL-KO); HL-WT had a greater impact on the concentration, composition, particle size, and catabolism of apoB-containing lipoproteins (apoB-Lps) and HDL. Importantly, consistent with the changes in apoB-Lps, atherosclerosis in LDLr-KOXHL-KO mice fed a regular chow diet (RCD) was reduced by both HL-WT and HL-S145G (by 71% and 51% in cross-sectional analysis, and by 85% and 67% in en face analysis; P < 0.05 for all). These data identify physiologically relevant but distinct roles for the lipolytic versus ligand-binding functions of HL in apoB-Lp metabolism and atherosclerosis and demonstrate that their differential effects on these processes are mediated by changes in catabolism via non-LDLr pathways. These changes, evident even in the presence of apoE, establish an antiatherogenic role of the ligand-binding function of HL in LDLr-deficient mice. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. RP Freeman, L (reprint author), NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. EM litaf@mail.nih.gov NR 48 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2007 VL 48 IS 1 BP 104 EP 113 DI 10.1194/jlr.M600321-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121AW UT WOS:000243130000011 PM 17071916 ER PT J AU Basso, F Freeman, LA Ko, C Joyce, C Amar, MJ Shamburek, RD Tansey, T Thomas, F Wu, J Paigen, B Remaley, AT Santamarina-Fojo, S Brewer, HB AF Basso, Federica Freeman, Lita A. Ko, Carol Joyce, Charles Amar, Marcelo J. Shamburek, Robert D. Tansey, Terese Thomas, Fairwell Wu, Justina Paigen, Beverly Remaley, Alan T. Santamarina-Fojo, Silvia Brewer, H. Bryan, Jr. TI Hepatic ABCG5/G8 overexpression reduces apoB-lipoproteins and atherosclerosis when cholesterol absorption is inhibited SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ABC transporters; ABCG subfamily; ezetimibe; non-HDL-cholesterol; biliary sterol secretion; hepatic cholesterol homeostasis; ApoB Kinetics ID LOW-DENSITY-LIPOPROTEIN; LIVER-X-RECEPTOR; APOLIPOPROTEIN-B; DIETARY-CHOLESTEROL; TRANSGENIC MICE; HEPG2 CELLS; INTRAHEPATIC CHOLESTEROL; AORTIC ATHEROSCLEROSIS; BETA-SITOSTEROLEMIA; MARKED REDUCTION AB We previously reported that liver-specific overexpression of ABCG5/G8 in mice is not atheroprotective, suggesting that increased biliary cholesterol secretion must be coupled with decreased intestinal cholesterol absorption to increase net sterol loss from the body and reduce atherosclerosis. To evaluate this hypothesis, we fed low density lipoprotein receptor-knockout (LDLr-KO) control andABCG5/ G8-transgenic (ABCG5/G8-Tg) 3LDLr-KO mice, which overexpress ABCG5/G8 only in liver, a Western diet containing ezetimibe to reduce intestinal cholesterol absorption. On this dietary regimen, liver-specific ABCG5/G8 overexpression increased hepatobiliary cholesterol concentration and secretion rates (1.5-fold and 1.9-fold, respectively), resulting in 1.6-fold increased fecal cholesterol excretion, decreased hepatic cholesterol, and increased (4.4-fold) de novo hepatic cholesterol synthesis versus LDLr-KO mice. Plasma lipids decreased (total cholesterol, 32%; cholesteryl ester, 32%; free cholesterol, 30%), mostly as a result of reduced non-high density lipoprotein-cholesterol and apolipoprotein B (apoB; 36% and 25%, respectively). ApoB-containing lipoproteins were smaller and lipid-depleted in ABCG5/ G8-TgXLDLr-KO mice. Kinetic studies revealed similar I-125-apoB intermediate density lipoprotein/LDL fractional catabolic rates, but apoB production rates were decreased 37% in ABCG5/G8-TgXLDLr-KO mice. Proximal aortic atherosclerosis decreased by 52% (male) and 59% (female) in ABCG5/G8-TgXLDLr-KO versus LDLr-KO mice fed the Western/ezetimibe diet. Thus, increased biliary secretion, resulting from hepatic ABCG5/G8 overexpression, reduces atherogenic risk in LDLr-KO mice fed a Western diet containing ezetimibe. These findings identify distinct roles for liver and intestinal ABCG5/G8 in modulating sterol metabolism and atherosclerosis. C1 NHLBI, Mol Dis Sect, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. RP Freeman, LA (reprint author), NHLBI, Mol Dis Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM litaf@mail.nih.gov NR 66 TC 28 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2007 VL 48 IS 1 BP 114 EP 126 DI 10.1194/jlr.M600353-JLR200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121AW UT WOS:000243130000012 PM 17060690 ER PT J AU Igarashi, M DeMar, JC Ma, KZ Chang, L Bell, JM Rapoport, SI AF Igarashi, Miki DeMar, James C., Jr. Ma, Kaizong Chang, Lisa Bell, Jane M. Rapoport, Stanley I. TI Upregulated liver conversion of alpha-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet SO JOURNAL OF LIPID RESEARCH LA English DT Article DE deprivation; incorporation; turnover; synthesis; pulse labeling; diet; brain; polyunsaturated fatty acid ID LOW-DENSITY-LIPOPROTEIN; POLYUNSATURATED FATTY-ACIDS; THIN-LAYER CHROMATOGRAPHY; AIN-93 PURIFIED DIETS; BLOOD-BRAIN-BARRIER; IN-VIVO; NUTRITIONAL DEPRIVATION; EICOSAPENTAENOIC ACID; KINETIC-ANALYSIS; AWAKE RATS AB We quantified incorporation rates of plasmaderived alpha-linolenic acid (alpha-LNA, 18:3n-3) into "stable" liver lipids and the conversion rate of alpha-LNA to docosahexaenoic acid (DHA, 22:6n-3) in male rats fed, after weaning, an n-3 PUFA-adequate diet (4.6% alpha-LNA, no DHA) or an n-3 PUFA-deficient diet (0.2% alpha-LNA, no DHA) for 15 weeks. Unanesthetized rats were infused intravenously with [1-C-14]alpha-LNA, and arterial plasma was sampled until the liver was micro-waved at 5 min. Unlabeled alpha-LNA and DHA concentrations in arterial plasma and liver were reduced > 90% by deprivation, whereas unlabeled arachidonic acid (20:4n-6) and docosapentaenoic acid (22:5n-6) concentrations were increased. Deprivation did not change alpha-LNA incorporation coefficients into stable liver lipids but increased synthesis-incorporation coefficients of DHA from alpha-LNA by 6.6-, 8.4-, and 2.3-fold in triacylglycerol, phospholipid, and cholesteryl ester, repectively. Assuming that synthesized-incorporated DHA even tually would be secreted within lipoproteins, calculated liver DHA secretion rates equaled 2.19 and 0.82 mu mol/day in the n-3 PUFA-adequate and -deprived rats, respectively. These rates exceed the published rates of brain DHA consumption by 6- and 10-fold, respectively, and should be sufficient to maintain normal and reduced brain DHA concentrations, respectively, in the two dietary conditions. Igarashi, M., J. C. DeMar, Jr., K. Ma, L. Chang, J. M. Bell, and S. I. Rapoport. Upregulated liver conversion of alpha-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Igarashi, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM mikii@mail.nih.gov RI Igarashi, Miki/B-1085-2017 FU Intramural NIH HHS NR 67 TC 73 Z9 75 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2007 VL 48 IS 1 BP 152 EP 164 DI 10.1194/jlr.M600396-JLR200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121AW UT WOS:000243130000016 PM 17050905 ER PT J AU Wei, Y Ito, Y AF Wei, Yun Ito, Yoichiro TI Isolation of hyperoside and luteolin-glucoside from Agrimonia pilosa Ledeb using stepwise elution by high-speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE stepwise countercurrent chromatography; isolation and purification; hyperoside; luteolin-glucoside; Agrimonia pilosa ledeb ID PREPARATIVE ISOLATION AB Preparative high-speed countercurrent chromatography was successfully used forisolation and purification of hyperoside and luteolin-glucoside from Agrimonia pilosa Ledeb. The separation was performed by stepwise clution with a pair of two-phase solvent systems composed of ethyl acetate-methanol-water at volume ratios of 50:1:50 and 5:1:5, which had been selected by analytical high-speed countercurrent chromatography (HSCCC). Using a preparative unit of the HSCCC centrifuge, about a 300 mg amount of the crude extract was separated, yielding 7.3 mg of hyperoside and 10.4 mg of luteolin-glucoside at a high purity of over 97%. C1 NHLBI, NIH, Ctr Biochem & Biophys, Bethesda, MD 20892 USA. Beijing Univ Chem Technol, Fac Sci, Dept Appl Chem, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, NIH, Ctr Biochem & Biophys, Bldg 50,Room 3334, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 13 TC 9 Z9 9 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2007 VL 30 IS 9-12 BP 1465 EP 1473 DI 10.1080/10826070701277091 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 173PC UT WOS:000246884000019 ER PT J AU Xie, Y Liang, Y Chen, HW Zhang, TY Ito, Y AF Xie, Y. Liang, Y. Chen, H.-W. Zhang, T.-Y. Ito, Y. TI Preparative isolation and purification of anthraquinones from Cassia seed by high-speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE high-speed countercurrent chromatography (HSCC); Cassia seed; anthraquinones; HPLC ID COIL PLANET CENTRIFUGE; SEPARATION; ISOFLAVONES; FLAVONOIDS; ALKALOIDS; EXTRACT; L. AB A high-speed countercurrent chromatography (HSCCC) technique in a semipreparative scale has been applied to separate and purify anthraquinones from the extract of Cassia seeds. A high efficiency of HSCCC separation was achieved on a two-phase solvent system of n-hexane-ethyl acetate-methanol-water (4:1:3:2, v/v/ v/v) by eluting the lower mobile phase at a flow rate of 1.5 mL/min under a revolution speed of 750 rpm. A total of five well separated peaks were obtained in the HSCCC chromatogram, and their purities were determined by HPLC-UV absorption spectrometry. These peaks were characterized by ESI-MSn and the data compared with the reference standards. Five peaks were identified as 1,2,6-trihydroxy-7, 8-dimethoxy-3- methylanthraquinone (7 mg), 1,2,6,8-tetrahydroxy-7-methoxy-3-methylanthraquinone (4 mg), 2-hydroxy- 1,6,7,8-teramethoxy-3-methylanthraquinone (9 mg), 6-dihydroxy-1,7,8-trimethoxy-3-methylanthraquinone (2 mg), and 1,2-dihydroxy-6,7,8tri-methoxy-3-methylanthraquinone (3 mg) from 100 mg of the sample. The purifies of obtained fractions were 98, 95, 96, 95, and 96%, respectively. HSCCC, thus, provides a cost effective alternative to preparative scale HPLC for the semi-preparative-scale separation and purification of anthraquinones from Cassia seeds. With appropriate modifications, the technique can also be applicable to other herbs in general. C1 NHLBI, NIH, Ctr Biochem & Biophys, Bethesda, MD 20892 USA. Beijing Inst New Technol Applicat, Beijing, Peoples R China. S China Normal Univ, Sch Chem & Environm, Inst Analyt Chem, Guangzhou, Peoples R China. RP Ito, Y (reprint author), NHLBI, NIH, Ctr Biochem & Biophys, Bldg 50,Room 3334,50 S Dr MSC 8014, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 17 TC 8 Z9 10 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2007 VL 30 IS 9-12 BP 1475 EP 1488 DI 10.1080/10826070701277117 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 173PC UT WOS:000246884000020 ER PT J AU Cao, XL Huang, DF Dong, YM Zhao, H Ito, Y AF Cao, Xueli Huang, Danfeng Dong, Yinmao Zhao, Hua Ito, Yoichiro TI Separation of aloins A and B from Aloe vera exudates by high speed countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE Aloe vera; aloins A and B; high speed countercurrent chromatography ID CONSTITUENTS AB Aloin is the main anthraquinone in aloe leaf, which occurs naturally as a mixture of two diastereoisomers, aloin A and aloin B, and currently served as one of the important control constituents in most of the commercial aloe products. High speed countercurrent chromatography (HSCCC) has been employed for the preparative separation of individual isomers combined with preseparation on silica gel chromatography. Three solvent systems composed of chloroform-methanol-water (4:2:3), ethyl acetate-methanol-water (5:1:5), and butanol-ethyl acetate-water (1:3:4) have been used in HSCCC. 6 g of extract of dry aloe leaf exudates yielded 202 mg of aloin A (> 98%) and 140 mg aloin B (> 96%). Their structures have been confirmed by FAB-MS and (HNMR)-H-1 through gradient enhanced nuclear overhauser effect spectroscopy (Goesy). C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. Beijing Technol & Business Univ, Sch Chem & Environm Engn, Beijing Key Lab Plant Resource Res & Dev, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 50,Rm 3334, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 6 TC 16 Z9 16 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2007 VL 30 IS 9-12 BP 1657 EP 1668 DI 10.1080/10826070701224887 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 173PC UT WOS:000246884000030 ER PT J AU Roman, JM Abbott, E Xu, X Fox, SD Veenstra, TD Issaq, HJ AF Roman, John M. Abbott, Eric Xu, Xia Fox, Stephen D. Veenstra, Timothy D. Issaq, Haleem J. TI Optimization of experimental parameters for packed column supercritical fluid chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE optimization; experimental parameters; packed column; supercritical fluid chromatography ID MASS SPECTROMETRY AB The present research is a study of experimental parameters that affect the resolution of a test mixture of estrogens by packed column supercritical fluid chromatography. The parameters that were evaluated included fluid flow rate, effect on resolution and retention times of the type and concentration of four organic modifiers, namely methanol, ethanol, isopropanol, and acetonitrile. Also, the effect of column type on the resolution of a mixture of estrogen metabolites was studied. Two packing materials cyanopropyl silica and Betasil diol silica were selected for this study. The following percentages of each of the packing materials were used in columns connected in series for the separation of the test mixture:100.0% CPS, 37.5% CPS/62.5% Diol, 50% CPS/50% Diol, 62.5 CPS/32.5% Diol, and 100.0% Diol. The results indicated that connecting two columns having the same dimensions (a ratio of one-to-one CPS/Diol) in series gave the best resolution. There was no effect on retention times or resolution when the two columns were reversed, i.e., column order has no effect. Also, retention times were a function of the organic modifier; methanol gave the shortest retention times, with approximately the same separation factor as the other three modifiers. C1 NCI, SAIC Frederick Inc, Adv Technol program, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, SAIC Frederick Inc, Adv Technol program, Lab Proteom & Analyt Technol, POB B, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov NR 8 TC 8 Z9 10 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2007 VL 30 IS 13-16 BP 2037 EP 2044 DI 10.1080/10826070701435046 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 197FF UT WOS:000248539300014 ER PT J AU Wang, X Liu, JH Zhang, TY Ito, YC AF Wang, Xiao Liu, Jianhua Zhang, Tianyou Ito, Yoichiro TI Rapid and simple method for quality control of raw materials of herbs by HSCCC SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE countercurrent chromatography; quality control; TCM ID COUNTER-CURRENT CHROMATOGRAPHY; PURIFICATION; SEPARATION; EFFICIENT AB The component of the traditional Chinese medicine (TCM) can be influenced by soils, climates, and growth stages. The quality of TCM mostly depends on the quality of the raw materials of the used herbs. A portable instrument and simple analysis method are urgently needed to be used for quality control of the raw herbs. In this study, analytical CCC (Model HS06) was applied to analyze three herbs including Fructus Arctii (Arctium lappa L.), Cortex Magnoliae Officinalis (Magnolia officinalis Rehd. et Wils.), and Fructus Psoraleae (Psoralea corylitolia L.), which were collected from different growth locations. The results showed that analytical CCC gave similar resolution as preparative CCC. In this analytical CCC operation, the crude sample is loaded directly without any pre-treatment, and only 1-10 mg sample is used for each injection. The separation time is often shorter than 1 hour and can compete with that of HPLC. HSCCC chromatograms can be used as the comparison patterns for the content control of the major bioactive compounds. The results demonstrated that it is feasible to control the raw herb's quality by analytical CCC. C1 NHLBI, Ctr Biochem & Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. Shandong Acad Sci, Shandong Anal & Test Ctr, Shandong, Peoples R China. Beijing UE Biotech Co Ltd, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, Natl Inst Hlth, Bldg 50,Room 3334, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov RI liang, xu/A-2138-2012 NR 8 TC 14 Z9 15 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2007 VL 30 IS 17 BP 2585 EP 2592 DI 10.1080/10826070701540522 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 225XL UT WOS:000250551400007 ER PT J AU Cao, XL Li, T Ito, YC AF Cao, Xue-Li Li, Ting Ito, Yoichiro TI Separation of chicken egg-white lysozyme by high-speed countercurrent chromatography using a reverse micellar system SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE high-speed countercurrent chromatography (HSCCC); Lysozyme; Reverse micellar extraction (RME) ID PURIFICATION; EXTRACTION; PROTEINS AB High-speed countercurrent chromatography (HSCCC) was employed for the first time to separate lysozyme from chicken egg-white using a reverse micellar system with 50 mM bis-(2-ethylhexyl) sulfosuccinate sodium (AOT) dissolved in isooctane and aqueous buffer. Lysozyme is separated from other main proteins through one step separation, and relatively high activity recovery (over 80%) can be achieved when applied to the purification of a preseparated sample, while a low recovery problem exists when applied to separate lysozyme from crude chicken eggwhite samples due to the interference of a large amount of other proteins. However, this method has advantages over traditional reverse micellar extraction (RME) for its simple continuous elution mode and high separation efficiency, and it is promising for scale-up. C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. Beijing Technol & Business Univ, Beijing Key Lab Plant Resource Res, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, 50 S Dr,Room 334, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 18 TC 4 Z9 5 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2007 VL 30 IS 17 BP 2593 EP 2603 DI 10.1080/10826070701540555 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 225XL UT WOS:000250551400008 ER PT J AU Shinomiya, K Kobayashi, K Oshima, H Okada, T Yanagidaira, K Ito, Y AF Shinomiya, Kazufusa Kobayashi, Koji Oshima, Hisashi Okada, Tadashi Yanagidaira, Kazuhiro Ito, Yoichiro TI Protein and cell separations using nonsynchronous coil planet centrifuge SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE nonsynchronous coil planet centrifuge; countercurrent chromatography; planetary motion; protein separation; polymer phase system; acceleration; elutriation; blood cell separation; mast cell separation ID COUNTERCURRENT CHROMATOGRAPHY; PARTITION CHROMATOGRAPHY; ROTATING SEALS; CORIOLIS-FORCE; MAST-CELLS; MOTION AB The nonsynchronous coil planet centrifuge has a unique mode of planetary motion in that it allows a freely adjustable rotational rate of the coiled separation column at a given revolution speed. This paper describes a series of studies using the apparatus fabricated in our laboratory on the countercurrent chromatographic separation of proteins with aqueous-aqueous polymer phase systems, experimental and theoretical analysis of the effect of planetary motion on protein separation, and application to elutriation of cells such as blood cell components and mast cells using a single-phase physiological buffer solution. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. Aichi Med Univ, Dept Physiol, Aichi, Japan. Nihon Univ, Coll Sci & Technol, Machining Technol Ctr, Tokyo 102, Japan. NIH, NHLBI, Ctr Biochem & Biophys, Bethesda, MD USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1,Narashinodai, Funabashi, Chiba 2748555, Japan. EM kshino@pha.nihon-u.ac.jp NR 18 TC 3 Z9 3 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2007 VL 30 IS 18 BP 2681 EP 2698 DI 10.1080/10826070701560579 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 225XM UT WOS:000250551500003 ER PT J AU de Sousa, PL de Souza, SL Silva, AC de Souza, RE de Castro, RM AF de Sousa, Paulo L. de Souza, Sandra L. Silva, Afonso C. de Souza, Ricardo E. de Castro, Raul Manhaes TI Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl2: changes in T-1 relaxation times during postnatal development SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE contrast agent; MEMRI; manganese; brain development; blood-brain barrier; T-1 relaxation time ID CENTRAL NERVOUS-SYSTEM; IN-VIVO; MOUSE-BRAIN; DIFFUSION TENSOR; 3D MRI; NEUROTOXICITY; EXPOSURE; MALNUTRITION; MYELINATION; METABOLISM AB Purpose: To measure regional T-1 changes in the postnatal rat brain following systemic administration of the contrast agent manganese chloride (MnCl2). Materials and Methods: MnCl2 (120 mM) was administered intravenously (i.v.) at 1.25 mL/hour to a dose of 175 mg/kg body weight. MRI experiments were performed on anaesthetized animals (32 male Wistar rats, postnatal days (PDs) 11, 16, 21, and 31) at 2.0 T. Regions of interest (ROIs) were drawn in sagittal slices and placed over five brain regions: olfactory bulb, cerebellum, cortex, thalamus, and hypothalamus. The signal intensities of each ROI were measured and fitted to a three-parameter function to estimate T-1 values. Results: In the brains of animals who did not receive the contrast agent (control group), we observed a consistent age-dependent decrease in T-1 values. In the brains of manganese-infused animals (manganese group), however, T-1 values were significantly lower than in the control group, indicating the uptake of manganese, but no dependence of T-1 on age was found. C1 CNRS, Ctr Biophys Mol, F-45071 Orleans 2, France. Univ Fed Pernambuco, Dept Anat, Recife, PE, Brazil. Univ Fed Pernambuco, Dept Fis, BR-50739 Recife, PE, Brazil. Univ Fed Pernambuco, Dept Nutr, Recife, PE, Brazil. NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP de Sousa, PL (reprint author), CNRS, Ctr Biophys Mol, Rue Charles Sadron, F-45071 Orleans 2, France. EM loureiro@cnrs-orleans.fr RI Silva, Afonso/A-7129-2009 FU Intramural NIH HHS NR 42 TC 15 Z9 15 U1 0 U2 1 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 JAN PY 2007 VL 25 IS 1 BP 32 EP 38 DI 10.1002/jmri.20792 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 122TV UT WOS:000243250800004 PM 17173304 ER PT J AU Velan, SS Durst, C Lemieux, SK Raylman, RR Sridhar, R Spencer, RG Hobbs, GR Thomas, MA AF Velan, S. Sendhil Durst, Christopher Lemieux, Susan K. Raylman, Raymond R. Sridhar, Rajagopalan Spencer, Richard G. Hobbs, Gerald R. Thomas, M. Albert TI Investigation of muscle lipid metabolism by localized one- and two-dimensional MRS techniques using a clinical 3T MRI/MRS scanner SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE IMCL; EMCL; unsaturated fatty acids; MRS; muscle ID MAGNETIC-RESONANCE-SPECTROSCOPY; FATTY-ACID-COMPOSITION; IN-VIVO; SKELETAL-MUSCLE; H-1-NMR SPECTROSCOPY; INSULIN-RESISTANCE; NEUTRAL LIPIDS; PHOSPHOLIPIDS; UNSATURATION; ACCUMULATION AB Purpose: To demonstrate the feasibility of estimating the relative intra- and extramyocellular lipid (IMCL and EMCL) pool magnitudes and calculating the degree of lipid unsaturation within soleus muscle using single-voxel localized one- and two-dimensional (1D and 2D) MR spectroscopy (MRS). Materials and Methods: Localized 1D point resolved spectroscopy (PRESS) and 2D correlation spectroscopy (LCOSY) were performed in incidental locations in the soleus muscle of 10 healthy subjects. A GE 3-T MRI/MRS scanner and a quadrature extremity transmit/receive coil was used . Results: The 1D and 2D MR spectra were used to compute IMCL/creatine (Cr) and ECML/Cr ratios. In addition to cross peaks between the methyl and methylene protons in the high-field region, the 2D spectra showed cross peaks due to J-coupling between allylic, diallylic methylene protons, and olefinic protons. The cross-peak volume ratios also provided a measure of double bonds, suggesting that this ratio can be used to assess unsaturation within IMCL and EMCL lipid pools. Conclusion: We have demonstrated the feasibility of detecting 2D cross peaks between different groups of IMCL and EMCL, including the unsaturated protons within these two lipids pools. This protocol may be easily extended to study the lipids present in other tissues. C1 W Virginia Univ, Ctr Adv Imaging & Radiol, Morgantown, WV 26506 USA. Howard Univ, Dept Radiat Oncol, Washington, DC 20059 USA. NIA, NMR Unit, NIH, Baltimore, MD 21224 USA. W Virginia Univ, Dept Stat, Morgantown, WV 26506 USA. Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. Howard Univ, Dept Genet & Human Genet, Washington, DC 20059 USA. Howard Univ, Ctr Canc, Washington, DC 20059 USA. RP Velan, SS (reprint author), W Virginia Univ, Ctr Adv Imaging & Radiol, Morgantown, WV 26506 USA. EM svelan@hsc.wvu.edu RI Thomas, m. albert/A-6176-2012; Velan, S. Sendhil/B-6374-2017; OI Velan, S. Sendhil/0000-0002-4096-0722; Durst, Christopher/0000-0003-4236-7524 FU Intramural NIH HHS; NCRR NIH HHS [2G12 RR003048-16A1]; NIMH NIH HHS [1R1MH065695-01A1] NR 40 TC 27 Z9 27 U1 0 U2 6 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 JAN PY 2007 VL 25 IS 1 BP 192 EP 199 DI 10.1002/jmri.20786 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 122TV UT WOS:000243250800024 PM 17152056 ER PT J AU Soto, E Espinoza, J Nien, JK Kusanovic, JP Erez, O Richani, K Santolaya-Forgas, J Romero, R AF Soto, Eleazar Espinoza, Jimmy Nien, Jyh Kae Kusanovic, Juan Pedro Erez, Offer Richani, Karina Santolaya-Forgas, Joaquin Romero, Roberto TI Human beta-defensin-2: A natural antimicrobial peptide present in amniotic fluid participates in the host response to microbial invasion of the amniotic cavity SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE antimicrobial peptide; preterm labor; human beta defensin-2; intra-amniotic infection; preterm PROM; amniotic fluid ID HUMAN BETA-DEFENSINS; CERVICAL-MUCUS PLUG; ANTIBACTERIAL PROPERTIES; INTRAUTERINE INFECTION; PRETERM BIRTH; PERIODONTAL INFECTION; HUMAN-NEUTROPHILS; EPITHELIAL-CELLS; INNATE IMMUNITY; VERNIX CASEOSA AB Objective. Human beta-defensin-2 (HBD-2) is a potent antimicrobial peptide that is part of the innate immune response. The purpose of this study was to determine whether HBD-2 is present in amniotic fluid and if its concentration changes with microbial invasion of the amniotic cavity (MIAC) and labor. Study design. Amniotic fluid was retrieved by amniocentesis from 318 patients in the following groups: (1) mid-trimester (n = 75); (2) term not in labor (n = 28) and in labor (n = 51); (3) preterm labor and intact membranes without MIAC who delivered at term (n 36), who delivered preterm without MIAC (n 52), and preterm labor with MIAC who delivered preterm (n 25); and (4) preterm premature rupture of membranes (preterm PROM) with (n 25) and without MIAC (n 26). MIAC was defined as a positive amniotic fluid culture for microorganisms. Amniotic fluid HBD-2 concentrations were determined using a sensitive and specific ELISA. Non-parametric statistics were used for analysis. Results. (1) HBD-2 was detected in all amniotic fluid samples; (2) the concentration of HBD-2 did not change with gestational age from mid-trimester to term (p = 0.8); (3) intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of HBD-2 in both women with preterm labor and intact membranes, and women with preterm PROM (p < 0.05 for each comparison); (4) patients with preterm labor and a negative amniotic fluid culture who delivered preterm had a higher median amniotic fluid HBD-2 concentration than those with preterm labor who delivered at term (p = 0.001); and (5) among patients with preterm labor without MIAC, those who had intra-amniotic inflammation (amniotic fluid white blood cell count 4100 cells per mL) had a higher median amniotic fluid concentration of HBD-2 than those without this condition (p < 0.002). Conclusion. (1) Amniotic fluid contains HBD-2, a natural antimicrobial peptide, and this may account for some of the antimicrobial activity of amniotic fluid; (2) amniotic fluid HBD-2 concentrations are increased in women with MIAC, regardless of the membrane status (intact membranes or PROM); and (3) we propose that amniotic fluid HBD-2 is part of the innate immune system within the amniotic cavity. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS [ZIA HD002400-18] NR 75 TC 37 Z9 37 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2007 VL 20 IS 1 BP 15 EP 22 DI 10.1080/14767050601036212 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 145KY UT WOS:000244865100003 PM 17437194 ER PT J AU Kusanovic, JP Espinoza, J Romero, R Hoppensteadt, D Nien, JK Kim, CJ Erez, O Soto, E Fareed, J Edwin, S Chaiworapongsa, T Than, NG Yoon, BH Gomez, R Papp, Z Hassan, SS AF Kusanovic, Juan Pedro Espinoza, Jimmy Romero, Roberto Hoppensteadt, Debra Nien, Jyh Kae Kim, Chong Jai Erez, Offer Soto, Eleazar Fareed, Jawed Edwin, Sam Chaiworapongsa, Tinnakorn Than, Nador G. Yoon, Bo Hyun Gomez, Ricardo Papp, Zoltan Hassan, Sonia S. TI Plasma protein Z concentrations in pregnant women with idiopathic intrauterine bleeding and in women with spontaneous preterm labor SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE coagulation; pregnancy; protein Z; amniotic fluid; parturition; thrombin; anti-protein Z antibodies; vaginal bleeding ID FACTOR-V-LEIDEN; Z DEFICIENCY; ISCHEMIC STROKE; AMNIOTIC-FLUID; PROTHROMBOTIC PHENOTYPE; INTRAAMNIOTIC INFECTION; PREMATURE LABOR; Z ANTIBODIES; PARTURITION; INHIBITOR AB Objectives. Preterm parturition has been associated with decidual vascular disorders and excessive thrombin generation. The objective of this study was to examine maternal plasma concentrations of protein Z in normal pregnancies, as well as in those presenting with spontaneous preterm labor (PTL) and intrauterine bleeding during pregnancy. Study design. A cross-sectional study was designed to include patients with preterm labor and intact membranes and those with idiopathic intrauterine bleeding during pregnancy. Protein Z plasma concentrations were measured in the following groups: (1) normal pregnant women (n = 71); (2) patients at term with (n = 67) and without labor (n = 88); (3) patients with spontaneous PTL before 34 weeks who were classified into: (a) PTL with intra-amniotic infection/inflammation (IAI; n = 35), (b) PTL without IAI (n = 54), and (c) patients with PTL who delivered at term (n = 49); and (4) patients with idiopathic intrauterine bleeding in the second and third trimester who were divided into: (a) subsequent spontaneous PTL and delivery, and (b) term delivery. Maternal plasma protein Z concentration was measured by a specific and sensitive immunoassay. Moreover, the amniotic fluid concentration of protein Z was determined in a subset of patients with preterm labor (n = 30). Results. (1) There was no correlation between maternal plasma protein Z concentration and gestational age in normal pregnant women. (2) The mean maternal plasma concentration of protein Z was significantly lower in women during spontaneous labor at term than in those not in labor (mean 2.15 mg/mL (95% CI 2.01-2.29) vs. mean 2.45 +/- 0.52 mg/mL (95% CI 2.34 -2.56), respectively; p = 0.001). (3) Women with PTL without IAI who delivered preterm had a significantly lower mean protein Z concentration than normal pregnant women (mean 2.12 mg/mL (95% CI 1.98-2.26) vs. mean 2.39 mg/mL (95% CI 2.28-2.5); p = 0.008). (4) Of interest, PTL with IAI was not associated with lower plasma concentrations of protein Z, nor were those with PTL who delivered at term (p > 0.05 for each). (5) No differences were found in the maternal plasma concentrations of anti-protein Z antibodies between normal pregnancies and those with spontaneous PTL. (6) Patients with idiopathic intrauterine bleeding who had spontaneous PTL and delivery had a significantly lower mean plasma protein Z concentration than those who delivered at term (mean 1.24 mg/mL (95% CI 1.08-1.4) vs. mean 1.49 +/- 0.47 mg/mL (95% CI 1.33-1.65), respectively; p = 0.03). (7) Amniotic fluid was found to contain immunoreactive protein Z. Conclusions. (1) Patients with PTL leading to preterm delivery in the absence of IAI had a significantly lower plasma concentration of protein Z than those with normal pregnancies. (2) Patients with idiopathic intrauterine bleeding and subsequently spontaneous PTL and delivery had a significantly lower plasma concentration of protein Z than those with idiopathic intrauterine bleeding who delivered at term. (3) Protein Z was present in the amniotic fluid of patients with PTL. Collectively, these observations suggest that a subgroup of patients with PTL have a hemostatic disorder that involves bleeding/thrombosis as a mechanism of disease. C1 NICHD, Perinatol Res Branch, DHHS, NIH, Detroit, MI 48201 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. Pontificia Univ Catolica Chile, CEDIP, Sotero Rio Hosp, Puente Alto, Chile. Semmelweis Univ, Dept Obstet & Gynecol 1, Budapest, Hungary. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch,DHHS,NIH, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS [Z01 HD002400-16] NR 88 TC 18 Z9 18 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2007 VL 20 IS 6 BP 453 EP 463 DI 10.1080/14767050701398272 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 183ZV UT WOS:000247611800004 PM 17674255 ER PT J AU Gotsch, F Romero, R Friel, L Kusanovic, JP Espinoza, J Erez, O Than, NG Mittal, P Edwin, S Yoon, BH Kim, CJ Mazaki-Tovi, S Chaiworapongsa, T Hassan, SS AF Gotsch, Francesca Romero, Roberto Friel, Lara Kusanovic, Juan Pedro Espinoza, Jimmy Erez, Offer Than, Nandor Gabor Mittal, Pooja Edwin, Samuel Yoon, Bo Hyun Kim, Chong Jai Mazaki-Tovi, Shali Chaiworapongsa, Tinnakorn Hassan, Sonia S. TI CXCL10/IP-10: A missing link between inflammation and anti-angiogenesis in preeclampsia? SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE pregnancy; CXCL10; IP-10; chemokine; chemotactic cytokine; small for gestational age; SGA; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; GAMMA-INDUCIBLE PROTEIN-10; CELL-ALPHA-CHEMOATTRACTANT; CHEMOKINE RECEPTOR CXCR3; TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; BED SPIRAL ARTERIES; MULTIPLE-SCLEROSIS PATIENTS; BOWEL ALLOGRAFT-REJECTION AB Objective. Interferon (IFN)-gamma inducible protein, CXCL10/IP-10, is a member of the CXC chemokine family with proinflammatory and anti-angiogenic properties. This chemokine has been proposed to be a key link between inflammation and angiogenesis. The aim of this study was to determine whether preeclampsia and delivery of a small for gestational age (SGA) neonate are associated with changes in maternal serum concentration of CXCL10/IP-10. Study design. This cross-sectional study included patients in the following groups: (1) non-pregnant women (N = 49); (2) women with normal pregnancies (N = 89); (3) patients with preeclampsia (N = 100); and (4) patients who delivered an SGA neonate (N = 78). SGA was defined as birth weight below the 10(th) percentile. Maternal serum concentrations of CXCL10/IP-10 were measured by sensitive immunoassay. Non-parametric statistics were used for analysis. Results. (1) Patients with normal pregnancies had a significantly higher median serum concentration of CXCL10/IP-10 than non-pregnant women (median 116.1 pg/mL, range 40.7-1314.3 vs. median 90.3 pg/mL, range 49.2-214.7, respectively; p = 0.002); (2) no significant correlation was found between maternal serum concentration of CXCL10/ IP-10 and gestational age (between 19 and 38 weeks); (3) there were no differences in median serum CXCL10/IP-10 concentrations between patients who delivered an SGA neonate and those with normal pregnancies (median 122.4 pg/mL, range 37.3-693.5 vs. median 116.1 pg/mL, range 40.7-1314.3, respectively; p > 0.05); (4) patients with preeclampsia had a higher median serum concentration of CXCL10/IP-10 than normal pregnant women (median 156.4 pg/mL, range 47.4-645.9 vs. median 116.1 pg/mL, range 40.7-1314.3, respectively; p < 0.05); (5) patients with preeclampsia had a higher median concentration of CXCL10/IP-10 than those who delivered an SGA neonate (median 156.4 pg/mL, range 47.4-645.9 vs. median 122.4 pg/mL, range 37.3-693.5, respectively; p < 0.05). Conclusions. Patients with preeclampsia have significantly higher serum concentrations of CXCL10/IP-10 than both normal pregnant women and mothers who have SGA neonates. These results are likely to reflect an anti-angiogenic state as well as an enhanced systemic inflammatory response in patients with preeclampsia. Alternatively, since preeclampsia and SGA share several mechanisms of disease, it is possible that a higher concentration of this chemokine may contribute to the clinical presentation of preeclampsia in patients with a similar intrauterine insult. C1 Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. NICHD, NIH, DHHS, Perinatol Res Branch, Bethesda, MD USA. Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. Wayne State Univ, Sch Med, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS [Z01 HD002400-16] NR 236 TC 37 Z9 39 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2007 VL 20 IS 11 BP 777 EP 792 DI 10.1080/14767050701483298 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 223WF UT WOS:000250403300001 PM 17943641 ER PT J AU Kusanovic, JP Romero, R Espinoza, J Gotsch, F Edwin, S Chaiworapongsa, T Mittal, P Soto, E Erez, O Mazaki-Tovi, S Than, NG Friel, LA Yoon, BH Mazor, M Hassan, SS AF Kusanovic, Juan Pedro Romero, Roberto Espinoza, Jimmy Gotsch, Francesca Edwin, Samuel Chaiworapongsa, Tinnakorn Mittal, Pooja Soto, Eleazar Erez, Offer Mazaki-Tovi, Shali Than, Nandor Gabor Friel, Lara A. Yoon, Bo Hyun Mazor, Moshe Hassan, Sonia S. TI Maternal serum soluble CD30 is increased in pregnancies complicated with acute pyelonephritis SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE sCD30; cytokines; Th2 immune response; SIRS; sepsis; pro-inflammatory; anti-inflammatory; pregnancy ID RESPIRATORY-DISTRESS SYNDROME; NECROSIS-FACTOR RECEPTOR; GENERALIZED SHWARTZMAN REACTION; INFLAMMATORY RESPONSE SYNDROME; B VIRUS-INFECTION; HODGKINS-DISEASE; KI-1 ANTIGEN; CELL-LINES; ANTIINFLAMMATORY CYTOKINES; EXPERIMENTAL PREECLAMPSIA AB Objectives. Normal pregnancy is characterized by activation of the innate immunity and suppression of the adaptive limb of the immune response. However, pregnant women are more susceptible to the effects of infection and microbial products than non-pregnant women. CD30 is a member of the tumor necrosis factor receptor superfamily and is preferentially expressed by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) is proposed to be an index of Th2 immune response. High serum concentrations of sCD30 have been found in the acute phase of viral infections, such as HIV1 and hepatitis B. There is, however, conflicting evidence about serum sCD30 concentration in patients with bacterial infections. The objective of this study was to determine whether there are changes in the serum concentration of sCD30 in pregnant women with pyelonephritis. Methods. This cross-sectional study included normal pregnant women (N = 89) and pregnant women with pyelonephritis (N = 41). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests were used for comparisons. A p value 50.05 was considered statistically significant. Results. (1) Pregnant women with pyelonephritis had a significantly higher median serum concentration of sCD30 than those with a normal pregnancy (median 44.3 U/mL, range 16 -352.5 vs. median 29.7 U/mL, range 12.2 -313.2, respectively; p < 0.001), and (2) No significant differences were found in the median maternal serum concentration of sCD30 between pregnant women with pyelonephritis who had a positive blood culture compared to those with a negative blood culture (median 47.7 U/mL, range 17.1 -118.8 vs. median 42.6 U/mL, range 16 -352.5, respectively; p = 0.86). Conclusions. Acute pyelonephritis during pregnancy is associated with a higher maternal serum concentration of sCD30 than normal pregnancy. This finding is novel and suggests that pregnant women with pyelonephritis may have a complex immune state in which there is activation of some components of what is considered a Th2 immune response. C1 NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA. EM nichdrprbchiefstaff@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS [Z01 HD002400-16, Z99 HD999999] NR 103 TC 12 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PY 2007 VL 20 IS 11 BP 803 EP 811 DI 10.1080/14767050701492851 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 223WF UT WOS:000250403300004 PM 17853184 ER PT J AU Diabate, A Dabire, RK Millogo, N Lehmann, T AF Diabate, Abdoulaye Dabire, Roch K. Millogo, Niama Lehmann, Tovi TI Evaluating the effect of postmating isolation between molecular forms of Anopheles gambiae (Diptera : Culicidae) SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE molecular forms; Anopheles gambiae; postmating ID INCIPIENT SPECIATION; CHROMOSOMAL FORM; WEST-AFRICA; COMPLEX; DIFFERENTIATION; DROSOPHILA; PATTERNS; GILES; AREA; MALI AB Multiple families representing all possible combinations of crosses between the two molecular forms of Anopheles gambiae sensu stricto Giles and their hybrids were set up using forced mating between offspring of wild-collected females. The results showed that the reproductive output of hybrids and their backcrosses was similar to that of the pure forms as measured by egg batch size, hatching rate, and larval development success. No sex ratio distortion was found among the offspring. We concluded that postmating developmental barriers do not contribute to the isolation between the molecular forms. C1 NIAID, NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA. RP Diabate, A (reprint author), NIAID, NIH, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM a_diabate@hotmail.com FU Intramural NIH HHS NR 24 TC 41 Z9 43 U1 2 U2 5 PU ENTOMOLOGICAL SOCIETY AMERICA PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD JAN PY 2007 VL 44 IS 1 BP 60 EP 64 DI 10.1603/0022-2585(2007)44[60:ETEOPI]2.0.CO;2 PG 5 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 124JZ UT WOS:000243365400008 PM 17294921 ER PT J AU Miller, FG Kaptchuk, TJ AF Miller, F. G. Kaptchuk, T. J. TI Acupuncture trials and informed consent SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO CONTROLS; ETHICAL-ISSUES; OSTEOARTHRITIS; NEEDLE; KNEE AB Participants are often not informed by investigators who conduct randomised, placebo-controlled acupuncture trials that they may receive a sham acupuncture intervention. Instead, they are told that one or more forms of acupuncture are being compared in the study. This deceptive disclosure practice lacks a compelling methodological rationale and violates the ethical requirement to obtain informed consent. Participants in placebo-controlled acupuncture trials should be provided an accurate disclosure regarding the use of sham acupuncture, consistent with the practice of placebo-controlled drug trials. C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Osher Inst, Boston, MA USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov FU NCCIH NIH HHS [R01 AT001414, 1 R01 AT001414-01] NR 23 TC 12 Z9 13 U1 0 U2 2 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 JAN 1 PY 2007 VL 33 IS 1 BP 43 EP 44 DI 10.1136/jme.2006.016535 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 123OV UT WOS:000243306100011 PM 17209110 ER PT J AU Hurst, SA Perrier, A Pegoraro, R Reiter-Theil, S Forde, R Slowther, AM Garrett-Mayer, E Danis, M AF Hurst, S. A. Perrier, A. Pegoraro, R. Reiter-Theil, S. Forde, R. Slowther, A-M Garrett-Mayer, E. Danis, M. TI Ethical difficulties in clinical practice: experiences of European doctors SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID CONSULTATION; CARE; SERVICE; COMMITTEES; BIOETHICS; DILEMMAS AB Background: Ethics support services are growing in Europe to help doctors in dealing with ethical difficulties. Currently, insufficient attention has been focused on the experiences of doctors who have faced ethical difficulties in these countries to provide an evidence base for the development of these services. Methods: A survey instrument was adapted to explore the types of ethical dilemma faced by European doctors, how they ranked the difficulty of these dilemmas, their satisfaction with the resolution of a recent ethically difficult case and the types of help they would consider useful. The questionnaire was translated and given to general internists in Norway, Switzerland, Italy and the UK. Results: Survey respondents (n = 656, response rate 43%) ranged in age from 28 to 82 years, and averaged 25 years in practice. Only a minority (17.6%) reported having access to ethics consultation in individual cases. The ethical difficulties most often reported as being encountered were uncertain or impaired decision-making capacity (94.8%), disagreement among caregivers (81.2%) and limitation of treatment at the end of life (79.3%). The frequency of most ethical difficulties varied among countries, as did the type of issue considered most difficult. The types of help most often identified as potentially useful were professional reassurance about the decision being correct (47.5%), someone capable of providing specific advice (41.1%), help in weighing outcomes (36%) and clarification of the issues (35.9%). Few of the types of help expected to be useful varied among countries. Conclusion: Cultural differences may indeed influence how doctors perceive ethical difficulties. The type of help needed, however, did not vary markedly. The general structure of ethics support services would not have to be radically altered to suit cultural variations among the surveyed countries. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Geneva, Fac Med, Inst Biomed Eth, Geneva, Switzerland. Univ Hosp Geneva, Gen Internal Med Serv, Geneva, Switzerland. Fdn Lanza, Padua, Italy. Univ Basel, Inst Appl Eth & Med Eth, Basel, Switzerland. Norwegian Med Assoc, Res Inst, Oslo, Norway. Univ Oxford, Ethox Ctr, Headington, England. Johns Hopkins Univ, Baltimore, MD USA. RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM mdanis@cc.nih.gov RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 29 TC 58 Z9 58 U1 2 U2 8 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 JAN 1 PY 2007 VL 33 IS 1 BP 51 EP 57 DI 10.1136/jme.2005.014266 PG 7 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 123OV UT WOS:000243306100014 PM 17209113 ER PT J AU Alter, BP Rosenberg, PS Brody, LC AF Alter, Blanche P. Rosenberg, Philip S. Brody, Lawrence C. TI Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2 SO JOURNAL OF MEDICAL GENETICS LA English DT Review ID SHARED GENETIC SUSCEPTIBILITY; FANCONI-ANEMIA; BREAST-CANCER; HELICASE BRIP1; BRAIN-TUMORS; BRCA2; MICE; LEUKEMIA; RISK; TUMORIGENESIS AB Patients with biallelic mutations in BRCA2 are in Fanconi anaemia group D1. We analysed the severity of the mutations in 27 cases, classified according to their association with breast cancer in heterozygotes, and their predicted functional effect. Twenty mutations were frameshifts or truncations, three involved splice sites, five were missense variants of unknown severity and two were benign polymorphisms. Five patients had VACTERL-H association. Leukaemia was reported in 13 patients, and solid tumours in 15; 6 patients had two or more malignancies. The cumulative probability of any malignancy was 97% by age 5.2 years. IVS7 + 1G -> A and IVS7 + 2T -> G were associated with AML, and 886delGT and 6174delT with brain tumours. However, patients with other alleles remained at very high risk of these events. Missense mutations formed a distinct cluster in a highly conserved region of the BRCA2 protein. The small group of patients with biallelic mutations in BRCA2 is distinctive in the severity of the phenotype, and early onset and high rates of leukaemia and specific solid tumours, and may comprise an extreme variant of Fanconi anaemia. Several of the alleles were not associated with cancer in presumed carriers, and thus counselling presents more uncertainties than usual. C1 NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NIH, Genome Technol Branch, NHGRI, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Alter, BP (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Execut Blvd,Execut Plaza S,Room 7020, Rockville, MD 20852 USA. EM alterb@mail.nih.gov FU Intramural NIH HHS NR 36 TC 106 Z9 108 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2007 VL 44 IS 1 BP 1 EP 9 DI 10.1136/jmg.2006.043257 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 123OR UT WOS:000243305700001 PM 16825431 ER PT J AU Jiao, XD Sultana, A Garg, P Ramamurthy, B Vemuganti, GK Gangopadhyay, N Hejtmancik, JF Kannabiran, C AF Jiao, Xiaodong Sultana, Afia Garg, Prashant Ramamurthy, Balasubramanya Vemuganti, Geeta K. Gangopadhyay, Nibaran Hejtmancik, J. Fielding Kannabiran, Chitra TI Autosomal recessive corneal endothelial dystrophy (CHED2) is associated with mutations in SLC4A11 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID POSTERIOR POLYMORPHOUS DYSTROPHY; GENETIC-LINKAGE; CELL-GROWTH; HEREDITARY; PROLIFERATION; CHROMOSOME-20; TRANSPORTERS AB Objective: To map and identify the gene for autosomal recessive congenital hereditary endothelial dystrophy (CHED2, OMIM 217700), a disorder characterised by diffuse bilateral corneal clouding that may lead to visual impairment and requiring corneal transplantation. Methods: Members of 16 families with autosomal recessive CHED were genotyped for 13 microsatellite markers at the CHED2 locus on chromosome 20p13-12. Two-point linkage analysis was carried out using the FASTLINK version of the MLINK program. Mutation screening was carried out by amplification of exons and flanking regions by polymerase chain reaction, followed by direct automated sequencing. Results: Linkage and haplotype analysis placed the disease locus within a 2.2 cM (1.3 Mb) interval flanked by D20S198 and D20S889, including SLC4A11. The maximum limit of detection score of 11.1 was obtained with D20S117 at theta=0. Sequencing of SLC4A11 showed homozygotic mutations in affected members from 12 of 16 families. Conclusion: These results confirm that mutations in the SLC4A11 gene cause autosomal recessive CHED. C1 LV Prasad Eye Inst, Hyderabad 500034, Andhra Pradesh, India. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Kannabiran, C (reprint author), LV Prasad Eye Inst, Banjara Hills, Hyderabad 500034, Andhra Pradesh, India. EM chitra@lvpei.org OI Kannabiran, Chitra/0000-0001-8435-0320 NR 18 TC 52 Z9 54 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2007 VL 44 IS 1 BP 64 EP 68 DI 10.1136/jmg.2006.044644 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 123OR UT WOS:000243305700010 PM 16825429 ER PT J AU Johnston, JJ Walker, RL Davis, S Facio, F Turner, JT Bick, DP Daentl, DL Ellison, JW Meltzer, PS Biesecker, LG AF Johnston, Jennifer J. Walker, Robert L. Davis, Sean Facio, Flavia Turner, Joyce T. Bick, David P. Daentl, Donna L. Ellison, Jay W. Meltzer, Paul S. Biesecker, Leslie G. TI Zoom-in comparative genomic hybridisation arrays for the characterisation of variable breakpoint contiguous gene syndromes SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID GREIG; MUTATIONS AB Contiguous gene syndromes cause disorders via haploinsufficiency for adjacent genes. Some contiguous gene syndromes (CGS) have stereotypical breakpoints, but others have variable breakpoints. In CGS that have variable breakpoints, the extent of the deletions may be correlated with severity. The Greig cephalopolysyndactyly contiguous gene syndrome (GCPSCGS) is a multiple malformation syndrome caused by haploinsufficiency of GLI3 and adjacent genes. In addition, non-CGS GCPS can be caused by deletions or duplications in GLI3. Although fluorescence in situ hybridisation (FISH) can identify large deletion mutations in patients with GCPS or GCPS-CGS, it is not practical for identification of small intragenic deletions or insertions, and it is difficult to accurately characterise the extent of the large deletions using this technique. We have designed a custom comparative genomic hybridisation (CGH) array that allows identification of deletions and duplications at kilobase resolution in the vicinity of GLI3. The array averages one probe every 730 bp for a total of about 14 000 probes over 10 Mb. We have analysed 16 individuals with known or suspected deletions or duplications. In 15 of 16 individuals (14 deletions and 1 duplication), the array confirmed the prior results. In the remaining patient, the normal CGH array result was correct, and the prior assessment was a false positive quantitative polymerase chain reaction result. We conclude that high-density CGH array analysis is more sensitive than FISH analysis for detecting deletions and provides clinically useful results on the extent of the deletion. We suggest that high-density CGH array analysis should replace FISH analysis for assessment of deletions and duplications in patients with contiguous gene syndromes caused by variable deletions. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. Shriners Hosp No Calif, Sacramento, CA USA. Mayo Clin, Dept Med Genet, Rochester, MN USA. RP Johnston, JJ (reprint author), Room 4C72,49 Convent Dr, Bethesda, MD 20892 USA. EM jjohnsto@mail.nih.gov NR 7 TC 9 Z9 10 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2007 VL 44 IS 1 AR e59 DI 10.1136/jmg.2006.042473 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 123OR UT WOS:000243305700013 PM 17098889 ER PT J AU Oh, B Kim, SY Kim, DJ Lee, JY Lee, JK Kimm, K Park, BL Shin, HD Kim, TH Park, EK Koh, JM Kim, GS AF Oh, Bermseok Kim, Shin-Yoon Kim, Duk Jae Lee, Jong Yong Lee, Jong-Keuk Kimm, Kuchan Park, Byung Lae Shin, Hyoung Doo Kim, Tae-Ho Park, Eui Kyun Koh, Jung-Min Kim, Ghi Su TI Associations of catalase gene polymorphisms with bone mineral density and bone turnover markers in postmenopausal women SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; DEFICIENCY; RISK; DIFFERENTIATION; OVEREXPRESSION; MITOCHONDRIA; OSTEOPOROSIS AB Background: Oxidative stress has been recently suggested to play a part in the development of osteoporosis. Catalase is a major antioxidant enzyme that detoxifies hydrogen peroxide by converting it into water and oxygen, thereby preventing cellular injury by oxidative stress. Aims: To examine the associations between the catalase gene (CAT) polymorphisms and bone mineral density (BMD) and bone turnover markers in postmenopausal Korean women. Methods: All exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Among 18 variants identified by a direct sequence method, four polymorphisms were selected and genotyped in all study participants (n = 560). BMD at the lumbar spine and proximal femur was measured using dual-energy x ray absorptiometry. Serum osteocalcin concentrations and bone-specific alkaline phosphatase activity were determined by an immunoradiometric assay and an immunoassay, respectively. Results: The mean (standard deviation) age of the participants was 59.4 (7.2) years. Multivariate analysis showed an association of the +22348C -> T polymorphism with BMD at the lumbar spine (p = 0.01 in the dominant model) and at femur neck (p = 0.05 in the dominant model), and with serum osteocalcin level (p = 0.008 in the dominant model). Haplotype analyses showed that HT4 (-20T, +144C, +22348T, +33078A) was significantly associated with higher BMD at various sites (p < 0.001 - 0.03) and with lower serum osteocalcin levels (p = 0.01 in the codominant model). Conclusions: These findings indicate that the +22348C -> T polymorphism and HT4 of CAT may be useful genetic markers for bone metabolism. C1 Univ Ulsan, Coll Med, Asan Med Ctr, Div Endocrinol & Metab, Seoul 138736, South Korea. NHGRI, NIH, Seoul, South Korea. Kyungpook Natl Univ Hosp, Skeletal Dis Genome Res Ctr, Taegu, South Korea. SNP Genet, Div Genet Epidemiol, Seoul, South Korea. RP Kim, GS (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Div Endocrinol & Metab, Seoul 138736, South Korea. EM gskim3@amc.seoul.kr NR 30 TC 21 Z9 22 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2007 VL 44 IS 1 AR e62 DI 10.1136/jmg.2006.042259 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 123OR UT WOS:000243305700016 PM 17209132 ER PT J AU Stewart, DR Corless, CL Rubin, BP Heinrich, MC Messiaen, LM Kessler, LJ Zhang, PJ Brooks, DG AF Stewart, Douglas R. Corless, Christopher L. Rubin, Brian P. Heinrich, Michael C. Messiaen, Ludwine M. Kessler, Lisa J. Zhang, Paul J. Brooks, David G. TI Mitotic recombination as evidence of alternative pathogenesis of gastrointestinal stromal tumours in neurofibromatosis type 1 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID NEURONAL INTESTINAL DYSPLASIA; NF1 GENE; VONRECKLINGHAUSENS DISEASE; INTERSTITIAL-CELLS; MUTATIONS; CAJAL; POLYMORPHISM; ASSOCIATION; HYPERPLASIA; INSIGHTS AB Background: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder resulting in the growth of a variety of tumours, and is inherited in an autosomal dominant pattern. Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that commonly harbour oncogenic mutations in KIT or PDGFRA and are thought to arise from the interstitial cells of Cajal (ICC; the pacemaker cells of the gut). Aim: To characterise two patients with NF1 and GISTs. Methods: Two patients were genotyped for germline mutations in NF1. GISTs from both patients were genotyped for somatic mutations in KIT and PDGFRA. Loss of heterozygosity (LOH) of NF1 in one GIST was assessed by genotyping seven micro-satellite markers spanning 2.39 Mb of the NF1 locus in the tumour and in genomic DNA. The known germline mutation in NF1 was confirmed in GIST DNA by sequencing. The copy number of the mutated NF1 allele was determined by multiplex ligand-dependent probe amplification. Results: GISTs from both patients were of wild type for mutations in KIT and PDGFRA. In the GIST with adequate DNA, all seven markers were informative and showed LOH at the NF1 locus; sequencing of NF1 from that GIST showed no wild-type sequence, suggesting that it was lost in the tumour. Multiplex ligand-dependent probe amplification analysis showed that two copies of all NF1 exons were present. Conclusions: This is the first evidence of mitotic recombination resulting in a reduction to homozygosity of a germline NF1 mutation in an NF1-associated GIST. We hypothesise that the LOH of NF1 and lack of KIT and PDGFRA mutations are evidence of an alternative pathogenesis in NF1-associated GISTs. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Univ Washington, Med Ctr, Dept Anat Pathol, Seattle, WA 98195 USA. Univ Alabama, Dept Genet, Birmingham, AL USA. Hosp Univ Penn, Dept Med Genet, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Merck & Co Inc, Whitehouse Stn, PA USA. RP Stewart, DR (reprint author), NHGRI, NIH, 49 Convent Dr,Bldg 49,Room 4A62, Bethesda, MD 20892 USA. EM drstewart@mail.nih.gov FU Intramural NIH HHS NR 44 TC 30 Z9 33 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2007 VL 44 IS 1 AR e61 DI 10.1136/jmg.2006.043075 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 123OR UT WOS:000243305700015 PM 17209131 ER PT J AU Atkinson, NL Massett, HA Mylks, C Hanna, B Deering, MJ Hesse, BW AF Atkinson, Nancy L. Massett, Holly A. Mylks, Christy Hanna, Bethany Deering, Mary Jo Hesse, Bradford W. TI User-centered research on breast cancer patient needs and prefferences of an internet-based clinical trial matching system SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE software design; user-computer interface; breast neoplasms; personal health records; qualitative research; user-centered design; human-computer interaction ID BARRIERS; PARTICIPATION; ENROLLMENT; RECRUITMENT AB Background: Internet-based clinical trial matching systems have the potential to streamline the search process for women with breast cancer seeking alternative treatments. A prototype system was developed to leverage the capabilities of a personal health record system for the purpose of identifying clinical trials. Objective: This study examines how breast cancer patients perceive and interact with a preliminary version of an Internet-based clinical trial matching system, while taking into account the demands of diagnosis and treatment decision making. Methods: Breast cancer patients participated in small group discussions and interacted with the prototype website in a two-phase qualitative research process. The first phase explored the experience of breast cancer patients (n=8) with treatment decision making, initial responses to the idea of Internet-based clinical trial matching systems, and reactions to the prototype site. In the second phase, a different set of breast cancer patients (n=7) reviewed revised website content and presentation and participated in a usability test in which they registered on the system and completed a personal health record to set up the matching process. Results: Participants were initially skeptical of the prototype system because it emphasized registration, had a complicated registration process, and asked for complex medical information. Changing content and attending to usability guidelines improved the experience for women in the second phase of the research and enabled the identification of functionality and content issues, such as lack of clear information and directions on how to use the system. Conclusions: This study showed that women felt favorably about the idea of using the Internet to search for clinical trials but that such a system needed to meet their expectations for credibility and privacy and be sensitive to their situation, Developers can meet these expectations by conforming to established usability guidelines and testing improvements with breast cancer patients. Future research is needed to verify these findings and to continue to improve systems of this nature. C1 [Atkinson, Nancy L.] Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. [Massett, Holly A.; Mylks, Christy] NCI, Operat Res Off, NIH, Rockville, MD USA. [Hanna, Bethany] Sch Nutr Assoc, Alexandria, VA USA. [Deering, Mary Jo] NCI, Ctr Bioinformat, NIH, Rockville, MD USA. [Hesse, Bradford W.] NCI, Hlth Commun & Informat Res Branch, NIH, Rockville, MD USA. RP Atkinson, NL (reprint author), Univ Maryland, Dept Publ & Community Hlth, Suite 2387 Valley Dr, College Pk, MD 20742 USA. EM atkinson@umd.edu NR 23 TC 13 Z9 13 U1 1 U2 5 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2007 VL 9 IS 2 AR e13 DI 10.2196/jmir.9.2.e13 PG 27 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 263IW UT WOS:000253211800008 PM 17513284 ER PT J AU Beckjord, EB Rutten, LJF Squiers, L Arora, NK Volckmann, L Moser, RP Hesse, BW AF Beckjord, Ellen Burke Rutten, Lila J. Finney Squiers, Linda Arora, Neeraj K. Volckmann, Lindsey Moser, Richard P. Hesse, Bradford W. TI Use of the Internet to communicate with health care providers in the United States: Estimates from the 2003 and 2005 Health Information National Trends Surveys (HINTS) SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE Internet; patient-provider communication; electronic mail; information services; trends and utilization; medical informatics; trends; health education; health services; demography; data collection; health care surveys; neoplasms; regression analysis ID E-MAIL COMMUNICATION; ELECTRONIC COMMUNICATION; PATIENT COMMUNICATION; ONLINE COMMUNICATION; FAMILY-PRACTICE; DIGITAL DIVIDE; PHYSICIANS USE; EMAIL; EHEALTH; SYSTEM AB Background: Despite substantial evidence that the public wants access to Internet-based communication with health care providers, online patient-provider communication remains relatively uncommon, and few studies have examined sociodemographic and health-related factors associated with the use of online communication with health care providers at a population level. Objective: The aim of the study was to use nationally representative data to report on the prevalence of and changes in use of online patient-provider communication in 2003 and 2005 and to describe sociodemographic and health-related factors associated with its use. Methods: Data for this study are from two iterations of the Health Information National Trends Survey (HINTS 2003, HINTS 2005). In both years, respondents were asked whether they had ever used email or the Internet to communicate with a doctor or a doctor's office. Adult Internet users in 2003 (n = 3982) and 2005 (n = 3244) were included in the present study. Multivariate logistic regression analysis was conducted to identify predictors for electronic communication with health care providers. Results: In 2003, 7% of Internet users had communicated online with an health care provider; this prevalence significantly increased to 10% in 2005. In multivariate analyses, Internet users with more years of education, who lived in a metro area, who reported poorer health status or who had a personal history of cancer were more likely to have used online patient-provider communication. Conclusions: Despite wide diffusion of the Internet, online patient-provider communication remains uncommon but is slowly increasing. Policy-level changes are needed to maximize the availability and effectiveness of online patient-provider communication for health care consumers and health care providers. Internet access remains a significant barrier to online patient-provider communication. C1 [Beckjord, Ellen Burke] NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Off Prevent Oncol,NIH, Bethesda, MD 20892 USA. [Beckjord, Ellen Burke; Rutten, Lila J. Finney; Volckmann, Lindsey; Moser, Richard P.; Hesse, Bradford W.] NCI, DCCPS, BRP, HCIRB,NIH, Bethesda, MD 20892 USA. [Squiers, Linda] NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. [Arora, Neeraj K.] NCI, DCCPS, Appl Res Program, Outcomes Res Branch,NIH, Bethesda, MD 20892 USA. RP Beckjord, EB (reprint author), NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Off Prevent Oncol,NIH, 6130 Execut Blvd EPN,4051A,MSC 7365, Bethesda, MD 20892 USA. EM beckjore@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 41 TC 80 Z9 81 U1 1 U2 17 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2007 VL 9 IS 3 AR e20 DI 10.2196/jmir.9.3.e20 PG 21 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 263IZ UT WOS:000253212100001 PM 17627929 ER PT J AU Keselman, A Tse, T Browne, A Ngo, L Zeng, Q AF Keselman, Alla Tse, Tony Browne, Allen Ngo, Long Zeng, Qing TI Assessing consumer health vocabulary familiarity: An exploratory study SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE consumer health vocabulary; patients; vocabulary; informatics; health education; readability; comprehension; health; evaluation studies ID LITERACY; INFORMATION; QUALITY; SPANISH AB Background: Accurate assessment of the difficulty of consumer health texts is a prerequisite for improving readability. General purpose readability formulas based primarily on word length are not well suited for the health domain, where short technical terms may be unfamiliar to consumers. To address this need, we previously developed a regression model for predicting "average familiarity" with consumer health vocabulary (CHV) terms. Objective: The primary goal was to evaluate the ability of the CHV term familiarity model to predict (1) surface-level familiarity of health-related terms and (2) understanding of the underlying meaning (concept familiarity) among actual consumers. Secondary goals involved exploring the effect of demographic factors (eg, health literacy) on surface-level and concept-level familiarity and describing the relationship between the two levels of familiarity. Methods: Survey instruments for assessing surface-level familiarity (45 items) and concept-level familiarity (15 items) were developed. All participants also completed a demographic survey and a standardized health literacy assessment, S-TOFHLA. Results: Based on surveys completed by 52 consumers, linear regression suggests that predicted CHV term familiarity is a statistically significantly predictor (P < .001) of participants' surface-level and concept-level familiarity performance. Health literacy was a statistically significant predictor of surface-level familiarity scores (P < .001); its effect on concept-level familiarity scores warrants further investigation (P = 0.06). Educational level was not a significant predictor of either type of familiarity. Participant scores indicated that conceptualization lagged behind recognition, especially for terms predicted as "likely to be familiar" (P = .006). Conclusions: This exploratory study suggests that the CHV term familiarity model is predictive of consumer recognition and understanding of terms in the health domain. Potential uses of such a model include readability formulas tailored to the consumer health domain and tools to "translate" professional medical documents into text that is more accessible to consumers. The study also highlights the usefulness of distinguishing between surface-level term familiarity and deeper concept understanding and presents one method for assessing familiarity at each level. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Decis Sci Grp, Boston, MA 02467 USA. NIH, Natl Lib Med, Bethesda, MD 20892 USA. Aquilent Inc, Laurel, MD USA. RP Keselman, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Decis Sci Grp, 75 Francis St, Boston, MA 02467 USA. EM qzeng@dsg.harvard.edu FU Intramural NIH HHS; NLM NIH HHS [R01 LM007222, R01 LM007222-05] NR 12 TC 20 Z9 20 U1 1 U2 5 PU JOURNAL OF MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2007 VL 9 IS 1 AR e5 DI 10.2196/jmir.9.1.e5 PG 7 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 148KT UT WOS:000245074100006 PM 17478414 ER PT J AU Zeng, QT Divita, G Keselman, A Crowell, J Browne, AC Goryachev, S Ngo, L AF Zeng, Qing T. Divita, Guy Keselman, Alla Crowell, Jon Browne, Allen C. Goryachev, Sergey Ngo, Long TI Term identification methods for consumer health vocabulary development SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE consumer health information; vocabulary; natural language processing ID TERMINOLOGY; INFORMATION AB Background: The development of consumer health information applications such as health education websites has motivated the research on consumer health vocabulary (CHV). Term identification is a critical task in vocabulary development. Because of the heterogeneity and ambiguity of consumer expressions, term identification for CHV is more challenging than for professional health vocabularies. Objective: For the development of a CHV, we explored several term identification methods, including collaborative human review and automated term recognition methods. Methods: A set of criteria was established to ensure consistency in the collaborative review, which analyzed 1893 strings. Using the results from the human review, we tested two automated methods-C-value formula and a logistic regression model. Results: The study identified 753 consumer terms and found the logistic regression model to be highly effective for CHV term identification (area under the receiver operating characteristic curve = 95.5%). Conclusions: The collaborative human review and logistic regression methods were effective for identifying terms for CHV development. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Decis Syst Grp, Boston, MA 02115 USA. NIH, LHNCBC, Natl Lib Med, DHHS, Bethesda, MD 20892 USA. Management Syst Designers Inc, Fairfax, VA USA. Aquilent Inc, Laurel, MD USA. RP Zeng, QT (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Decis Syst Grp, Thorn 304,75 Francis St, Boston, MA 02115 USA. EM qzeng@dsg.harvard.edu FU Intramural NIH HHS; NLM NIH HHS [R01 LM07222, R01 LM007222] NR 31 TC 15 Z9 15 U1 0 U2 6 PU JOURNAL MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PY 2007 VL 9 IS 1 AR e4 DI 10.2196/jmir.9.1.e4 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 148KT UT WOS:000245074100005 PM 17478413 ER PT J AU Yabroff, KR Freedman, A Brown, ML Ballard-Barbash, R McNeel, T Taplin, S AF Yabroff, K. Robin } Freedman, Andrew Brown, Martin L. Ballard-Barbash, Rachel McNeel, Timothy Taplin, Stephen TI Trends in abnormal cancer screening results in the United States of America SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID INTERLABORATORY COMPARISON PROGRAM; CURRENT LABORATORY PRACTICES; HEALTH INTERVIEW SURVEY; SERVICES TASK-FORCE; CERVICAL-CANCER; CERVICOVAGINAL CYTOLOGY; COST-EFFECTIVENESS; COLORECTAL-CANCER; CUMULATIVE RISK; MAMMOGRAPHY AB Background Although recent trends in the use of recommended breast and cervical cancer screening have been well documented in the USA, little is known about trends in the prevalence of abnormal screening results. Methods Trends in abnormal screening results for mammography and Papanicolaou (Pap) smear were assessed descriptively using data from the 1987 and 2000 National Health Interview Surveys. Estimates were stratified by sociodemographic characteristics of the populations who reported ever receiving screening. All comparisons were evaluated with two-sided tests of statistical significance. Results The age-standardized prevalence of abnormal Pap smears increased from 12.9% (95% confidence interval [CI] 12.1-13.8%) of women ever screened in 1987 to 20.3% (95% CI 19.5-21.0%) in 2000, and the age-standardized prevalence of abnormal mammogram results increased from 18.8% (95% CI 17.0-20.7%) to 21.6% (95% CI 20.5-22.7%) of women ever screened over the same period. Among women aged 40 years and older who reported ever receiving both a Pap smear and a mammogram, 29.6% (95% CI: 27.3-32.2%) in 1987 and 35% (95% CI: 33.8-36.2%) in 2000 reported either an abnormal Pap smear or an abnormal mammogram. In 2000, abnormal screening results were positively associated with reported frequency of recent screening (P<0.001). Conclusions A substantial portion of women in the USA reporting cancer screening also report having had abnormal results, although the magnitude of trends between 1987 and 2000 vary by screening test. Additional research is needed to assess the relative contributions of changes in CIassification of test results, test characteristics and changes in underlying screening histories to increases in abnormal screening results. C1 NCI, Hlth Serv, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Hlth Serv & Econ, Bethesda, MD 20892 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM yabroffr@ail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 44 TC 6 Z9 6 U1 0 U2 4 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2007 VL 14 IS 2 BP 67 EP 72 DI 10.1258/096914107781261909 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 214EI UT WOS:000249718400004 PM 17626704 ER PT J AU Boeshans, KM Mueser, TC Ahvazi, B AF Boeshans, Karen M. Mueser, Timothy C. Ahvazi, Bijan TI A three-dimensional model of the human transglutaminase 1: insights into the understanding of lamellar ichthyosis SO JOURNAL OF MOLECULAR MODELING LA English DT Article DE keratinocyte transglutaminase 1; lamellar ichthyosis; mutations; metal ions; isomerization; molecular modeling ID RECESSIVE CONGENITAL ICHTHYOSIS; CIS PEPTIDE-BONDS; KERATINOCYTE TRANSGLUTAMINASE; STRUCTURAL BASIS; CIS/TRANS ISOMERIZATION; PROTEIN STRUCTURES; CRYSTAL-STRUCTURE; CALCIUM-IONS; MUTATIONS; ENZYME AB The stratum corneum, the outer layer of the epidermis, serves as a protective barrier to isolate the skin from the external environment. Keratinocyte transglutaminase 1 (TGase 1) catalyzes amide crosslinking between glutamine and lysine residues on precursor proteins forming the impermeable layers of the epidermal cell envelopes (CE), the highly insoluble membranous structures of the stratum corneum. Patients with the autosomal recessive skin disorder lamellar ichthyosis (LI) appear to have deficient cross-linking of the cell envelope due to mutations identified in TGase 1, linking this enzyme to LI. In the absence of a crystal structure, molecular modeling was used to generate the structure of TGase 1. We have mapped the known mutations of TGase 1 from our survey obtained from a search of PubMed and successfully predicted the impact of these mutations on LI. Furthermore, we have identified Ca(2+) binding sites and propose that Ca(2+) induces a cis to trans isomerization in residues near the active site as part of the enzyme transamidation activation. Docking experiments suggest that substrate binding subsequently induces the reverse cis to trans isomerization, which may be a significant part of the catalytic process. These results give an interpretation at the molecular level of previously reported mutations and lead to further insights into the structural model of TGase 1, providing a new basis for understanding LI. C1 NIAMS, Xray Crystallog Facil, Bethesda, MD 20892 USA. NIAMSD, Xray Crystallog Fac, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. Univ Toledo, Dept Chem, Toledo, OH 43606 USA. RP Ahvazi, B (reprint author), NIAMS, Xray Crystallog Facil, MSC 8024,50 South Dr,Bldg 50,Room 1345, Bethesda, MD 20892 USA. EM ahvazib@mail.nih.gov FU Intramural NIH HHS NR 50 TC 18 Z9 20 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1610-2940 J9 J MOL MODEL JI J. Mol. Model. PD JAN PY 2007 VL 13 IS 1 BP 233 EP 246 DI 10.1007/s00894-006-0144-9 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Chemistry; Computer Science GA 109RQ UT WOS:000242326700025 PM 17024410 ER PT J AU Polozova, A Salem, N AF Polozova, Alla Salem, Norman, Jr. TI Role of liver and plasma lipoproteins in selective transport of n-3 fatty acids to tissues: A comparative study of C-14-DHA and H-3-oleic acid tracers SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD DE omega-3; docosahexaenoic acid; DHA; lipoproteins; fatty acid transport ID RECEPTOR CLASS-B; SUDDEN CARDIAC DEATH; BLOOD-BRAIN-BARRIER; PERFORMANCE LIQUID-CHROMATOGRAPHY; CAPILLARY ENDOTHELIAL-CELLS; DOCOSAHEXAENOIC ACID; FISH-OIL; BINDING PROTEIN; DIFFERENTIAL INCORPORATION; DIETARY-CHOLESTEROL AB We conducted a study aimed at a direct comparison of the plasma dynamics and uptake of docosahexaenoic (DHA) and oleic (OA) fatty acids by various organs. C-14-DHA and H-3-OA were intravenously co-injected into mice. At 5 min after injection, more than 40% of the C-14-DHA, but less than 20% of the H-3-OA, labels was associated with the liver. Heart uptake of C-14-DHA was three to four times greater compared to the H-3-OA label. Brain incorporation of C-14-DHA slowly rose to 0.7% at 24 h, but it remained at the 1-1.5% level for 3H-OA. Total 14 C activity in plasma reached 2% of the injected dose at 20 min and leveled off at 0.5% after 1.5 h. Fifteen percent of C-14-DHA plasma activity at 30 min was associated with non-esterified fatty acids, whereas about 85% was recovered in triglycerides in very low-density lipoprotem (VLDL) and LDL fractions. Only 30% of H-3-OA derived activity was found in the VLDL fraction at 30 min. All H-3 activity in plasma at later time points was in catabolite fractions. These findings demonstrate that liver plays an important role in the initial selectivity for DHA. It is likely that DHA is specifically taken up by liver, esterified, loaded into lipoproteins, and then delivered to brain, heart, and other target tissues. C1 NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. RP Salem, N (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 5625 Fishers Lane,Room 3N-07, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov NR 70 TC 28 Z9 28 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 56 EP 66 DI 10.1007/s12031-007-0039-y PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800010 PM 17901547 ER PT J AU Guo, MQ Stockert, L Akbar, M Kim, HY AF Guo, Mingquan Stockert, Lyubov Akbar, Mohammed Kim, Hee-Yong TI Neuronal specific increase of phosphatidylserine by docosahexaenoic acid SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD DE phosphatidylserine; docosahexaenoic acid; neuronal cells; phosphatidylethanolamine; phosphatidylserine synthase ID HAMSTER OVARY CELLS; RAT-BRAIN; BIOSYNTHETIC DEFECT; MASS-SPECTROMETRY; LIVER; CLONING; OVEREXPRESSION; DECARBOXYLASE; INHIBITION; DEFICIENCY AB Phosphatidylserine (PS), the major acidic phospholipid class in eukaryotic biomembranes, plays an important role in various signaling pathways. We have previously demonstrated that docosahexaenoic acid (DHA, 22:6n-3) positively modulates PS biosynthesis and accumulation in neuronal cells, promoting survival. In this paper, we demonstrate that the increase of PS levels upon DHA enrichment is not a universal mechanism, but specific to neuronal cells. When cells were enriched with 20 mu M DHA, 18:0, 22:6-PS increased in both neuronal (Neuro, 2A) and non-neuronal cells (Chinese hamster ovary K1 cells, NIH-3T3, and human embryonic kidney cells). However, the increase of the total PS level was observed only in Neuro 2A cells because of the fact that other PS species, such as 18:0, 18:1-PS and 18:1, 18:1-PS decreased significantly in non-neuronal cells, compensating for the increase of 18:0, 22:6-PS. DHA enrichment did not affect the messenger RNA levels of PS synthase I (PSSI) and PSS2. Over-expression of genes encoding PSS1 or PSS2 altered neither the PS level nor the effect of DHA on PS increase in both neuronal and non-neuronal cells. From these results, it is concluded that the PS increase by DHA, specifically observed in neuronal cells, may represent a unique mechanism for expanding the PS pool so far known in mammalian cells. C1 NIAAA, Lab Mol Signaling, Natl Inst Hlth, Bethesda, MD 20852 USA. RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, Natl Inst Hlth, 5625 Fishers Ln,Room 3N-07, Bethesda, MD 20852 USA. EM hykim@nih.gov FU Intramural NIH HHS NR 34 TC 21 Z9 22 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 67 EP 73 DI 10.1007/s12031-007-0046-z PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800011 PM 17901548 ER PT J AU Lovinger, DM AF Lovinger, David M. TI Endocannabinoid liberation from neurons in transsynaptic signaling SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD DE endocannabinoids transsynaptic signaling; Cannabis sativa ID LONG-TERM DEPRESSION; ENDOGENOUS CANNABINOID ANANDAMIDE; CEREBELLAR PURKINJE-CELLS; ACID-BINDING-PROTEINS; METABOTROPIC GLUTAMATE; PRESYNAPTIC INHIBITION; RETROGRADE INHIBITION; MEMBRANE-TRANSPORT; FATTY-ACIDS; ACTIVATION AB Endocannabinoids are fatty acid derivatives that have a variety of biological actions, most notably via activation of the cannabinoid receptors. These receptors are also targets for drugs derived from Cannabis sativa. In the nervous system, endocannabinoids act as neuromodulators that depress neurotransmitter release at the presynaptic terminal. In most instances of neural endocannabinoid signaling, the compounds appear to be released from the postsynaptic neuron to act on the presynaptic terminal in a "retrograde" manner. Several common mechanisms involved in postsynaptic endocannabinoid production and presynaptic depression produced via activation of the CB1 cannabinoid receptor have been identified. However, significant problems remain in defining the mechanisms underlying endocannabinoid production, release, and movement across the membrane. These issues are discussed in the present review. C1 NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, Div Intramural Clin & Basic Res,NIH, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, Div Intramural Clin & Basic Res,NIH, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov NR 62 TC 15 Z9 16 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 87 EP 93 DI 10.1007/s12031-007-0043-2 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800014 PM 17901551 ER PT J AU Casas, R Dustman, J Teague, W Gawrisch, K AF Casas, Rachel Dustman, John Teague, Walter Gawrisch, Klaus TI The influence of hydrocarbon chain length, polyunsaturation, and of lipid headgroups on lateral diffusion rates of lipids SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIAAA, NIH, Membrane Biochem & Biophys Lab, Rockville, MD 20852 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 129 EP 129 DI 10.1007/s12031-007-0057-9 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800022 ER PT J AU Eldho, NV Feller, SE Tristram-Nagle, S Polozov, IV Gawrisch, K AF Eldho, Nadukkudy V. Feller, Scott E. Tristram-Nagle, Stephanie Polozov, Ivan V. Gawrisch, Klaus TI Polyunsaturated docosahexaenoic acid vs docosapentaenoic acid - Differences in lipid matrix properties from the loss of one double bond SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIAAA, NIH, Membrane Biochem & Biophys Lab, Rockville, MD 47933 USA. Wabash Coll, Dept Chem, Crawfordsville, IN 15213 USA. Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA USA. RI Tristram-Nagle, Prof. Stephanie/N-7811-2014 OI Tristram-Nagle, Prof. Stephanie/0000-0003-2271-7056 NR 0 TC 0 Z9 0 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 129 EP 130 DI 10.1007/s12031-007-0057-9 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800023 ER PT J AU Castagnet, PI Nussbaum, RL Murphy, EJ AF Castagnet, P. I. Nussbaum, R. L. Murphy, E. J. TI alpha-synuclein gene ablation decreases astrocyte fatty acid uptake and alters fatty acid trafficking SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 134 EP 134 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800032 ER PT J AU Golovko, MY Castagnet, PI Nussbaum, RL Murphy, EJ AF Golovko, Mikhail Y. Castagnet, Paula I. Nussbaum, Robert L. Murphy, Eric J. TI alpha-synuclein expression enhances brain palmitate uptake and difrerentially affects palmitate incorporation and turnover in brain phospholipids SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Sch Med & Hlth Sci, Grand Forks, ND 58202 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 134 EP 134 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800033 ER PT J AU Calderon, F Kim, HY AF Calderon, Frances Kim, Hee-Yong TI Role of docosahexaenoic acid and RXR receptor on neurite growth in hippocampal neurons and neuroblastoma cells SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIAAA, Sect Mass Spectrometry, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 135 EP 136 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800036 ER PT J AU Demar, JC Ma, K Chang, L Bell, J Rapoport, SI AF Demar, James C. Ma, Kaizong Chang, Lisa Bell, Jane Rapoport, Stanley I. TI Brain conversion of linoleic acid to arachidonic acid is not a major source of the arachidonate found in brain phospholipids of adult rats SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIA, NIH, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 135 EP 135 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800035 ER PT J AU Lee, HJ Rao, J Chang, L Rapoport, SI Bazinet, RP AF Lee, Ho-Joo Rao, Jagadeesh Chang, Lisa Rapoport, Stanley I. Bazinet, Richard P. TI The effects of carbamazepine on the metabolism of arachidonic and docosahexaenoic acid in the brain of the awake rat SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIA, NIH, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. EM hojoolee@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 139 EP 139 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800044 ER PT J AU Maoz, D Mayette, J Nguyen, HN Lee, HJ Rapoport, SI Bhattachajee, AK Bazinet, RP AF Maoz, Daniel Mayette, Jana Nguyen, Henry N. Lee, Ho-Joo Rapoport, Stanley I. Bhattachajee, Abesh K. Bazinet, Richard P. TI Regional effects of aging on the fatty acid concentration of various phospholipids in the rhesus monkey brain SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIA, NIH, Brain Physiol & Metab Sect, Rockville, MD 20852 USA. EM danielmaoz@walla.co.il NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 139 EP 139 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800043 ER PT J AU Akbar, M Kim, HY AF Akbar, Mohammed Kim, Hee-Yong TI Docosahexaenoic acid: A positive cross-talk mediator between membrane phosphatidylserine and akt kinase SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIAAA, Sect Mass Spectrometry, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 140 EP 140 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800045 ER PT J AU Niu, SL Mitchell, DC Lim, SY Wen, ZM Kim, HY Salem, NJ Litman, BJ AF Niu, Shui-Lin Mitchell, Drake C. Lim, Sun-Young Wen, Zhi-Ming Kim, Hee-Yong Salem, Norman J. Litman, Burton J. TI N-3 fatty acid deficiency leads to reduced g-protein-coupiled signaling efficiency in retinal rod outer segments SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIAAA, Lab Membrane Biophys & Biochem, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 140 EP 141 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800047 ER PT J AU Stockert, L Guo, MQ Akbar, M Kim, HY AF Stockert, Lyubov Guo, Mingquan Akbar, Mohammed Kim, Hee-Yong TI Neuronal phosphatidylserine accumulation modulated by docosahexaenoic acid and PSSI and PSS2 gene silencing SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIAAA, Sect Mass Spectrometry, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 140 EP 140 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800046 ER PT J AU Polozova, A Mook, W Salem, N AF Polozova, Alla Mook, William Salem, Norman, Jr. TI Effect of dietary DHA depletion on plasma lipoprotein content SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 141 EP 142 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800049 ER PT J AU Bailey, BW Lewis, J Mitchell, DC AF Bailey, Brian W. Lewis, Jennifer Mitchell, Drake C. TI Flumazenil binding in synaptosomes varies between female and male rats fed an n-3-deficient diet SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NIAAA, NIH, Lab Membrane Biochem & Biophys, Bethesda, MD USA. RI Bailey, Brian/B-1732-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 142 EP 143 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800051 ER PT J AU SanGiovanni, JP Chew, EY Sperduto, RD Ferris, FL AF SanGiovanni, J. P. Chew, E. Y. Sperduto, R. D. Ferris, F. L. CA AREDS Res Grp TI The relationship of omega-3 long-chain polyunsaturated fatty acid intake and regular aspirin use with Neovascular age-related macular degeneration SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT International Workshop on Brain Uptake and Utilization of Fatty Acids, Lipids and Lipoproteins CY OCT 07-09, 2004 CL Bethesda, MD C1 NEI, NIH, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. RI SanGiovanni, John Paul/A-7605-2008 NR 0 TC 1 Z9 1 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 1 BP 142 EP 142 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 213MD UT WOS:000249670800050 ER PT J AU Eliezer, G Joanna, MH Efrat, D Conor, MS Gozes, I AF Eliezer, Giladi Joanna, M. Hill Efrat, Dresner Conor, M. Stack Gozes, Illana TI Vasoactive intestinal peptide (VIP) regulates activity-dependent neuroprotective protein (ADNP) expression in vivo SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article ID EMBRYONIC GROWTH; GENE-EXPRESSION; MOUSE; ANTAGONIST; MICE; EMBRYOGENESIS; BEHAVIOR; BRAIN; BLOCKADE; STRATEGY AB Vasoactive intestinal peptide (VIP) is an important mediator of development during the neural tube closure period of embryogenesis and may regulate, in part, the expression of activity-dependent neuroprotective protein (ADNP), which is essential for neural tube closure and embryogenesis. To evaluate the impact of VIP expression in vivo on ADNP and the related protein ADNP2 the current study examined gene expression in adult wild-type (VIP +/ +) and VIP null (VIP -/-) offspring of VIP deficient mothers (VIP+/-) comparing them to wild-type offspring of wild-type mothers. Quantitative real time polymerase chain reaction (PCR), using an ABI Prisma cycler revealed regionally specific reductions of ADNP mRNA in the brains of VIP null mice compared with the brains of wildtype offspring of a wild-type mother. ADNP was significantly reduced in the cortex and hypothalamus of VIP null mice, but not in the hippocampus or thalamus. ADNP2 exhibited a similar pattern but reached a statistically significant reduction only in the hypothalamus. The mRNA for ADNP and ADNP2 also tended to be reduced in the cortex and hippocampus of the wild-type littermates of the VIP null mice, indicating that the VIP genotype of the mother may have had an impact on the ADNP expression of her offspring, regardless of their own VIP genotype. These results showed that VIP regulated brain ADNP expression in a regionally specific manner and indicated that both maternal and offspring VIP genotype may influence ADNP expression in the brain. C1 Tel Aviv Univ, Dept Human Mol Genet & Biochem, Adams Super Ctr Brain Studies, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Dept Human Mol Genet, LEG fMRI Inst, IL-69978 Tel Aviv, Israel. Cornell Univ, Dept Neurobiol & Behav, Ithaca, NY 14853 USA. NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. RP Gozes, I (reprint author), Tel Aviv Univ, Dept Human Mol Genet & Biochem, Adams Super Ctr Brain Studies, IL-69978 Tel Aviv, Israel. EM igozes@post.tau.ac.il NR 36 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 EI 1559-1166 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 278 EP 283 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900007 ER PT J AU Weihel, E Scafer, MKH Kashiotis, AM Mahal, T Wiesenfeld-Hallin, Z Erickson, J Eiden, LE AF Weihel, Eberhard Scafer, Martin K-H Kashiotis, Anna M. Mahal, Tobias Wiesenfeld-Hallin, Zsuzsanna Erickson, Jeff Eiden, Lee E. TI Pre- and postsynaptic control of spinal and supraspinal glutamatergic neurotransmission by pacap during neuropathic pain SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT C1 Univ Marburg, Med Ctr, Inst Anat, Marburg, Germany. Karolinska Inst, Stockholm, Sweden. LSU, Ctr Neurosci, New Orleans, LA USA. NIMH, Mol Neurosci Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 311 EP 311 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900016 ER PT J AU Ravni, A Au, R Chow, BKC Fournier, A Vaudry, H Eiden, LE Vaudry, D AF Ravni, Aurelia Au, Ruby Chow, Bill K. C. Fournier, Alain Vaudry, Hubert Eiden, Lee E. Vaudry, David TI Serpin b1a controls the antiapoptotic effects of PACAP and NGF in PC12 cells SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT C1 Univ Rouen, INSERM U413, Lab Cellular & Mol Neuroendocrinol, IFRMP 23, F-76821 Mont St Aignan, France. Univ Hong Kong, Dept Zool, Hong Kong, Hong Kong, Peoples R China. Univ Quebec, Inst Natl Rech Sci Sante, Inst Armand Frappier, Pointe Claire, PQ H9R 1G6, Canada. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD USA. RI Chow, Billy/D-3064-2009 OI Chow, Billy/0000-0003-3390-0307 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 313 EP 314 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900021 ER PT J AU Mustafal, T Walsh, J Maurizio, G Eiden, LE AF Mustafal, Tomris Walsh, James Maurizio, Grimaldi Eiden, Lee E. TI The bovine PACl-hop receptor: insights into PACAP signaling through calcium in neural cell function SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT C1 NIMH, Mol Neurosci Sect, Bethesda, MD 20892 USA. So Res Inst, Neuropharmacol Lab, Birmingham, AL 35205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 318 EP 318 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900033 ER PT J AU Jensen, RT Moody, TW Ito, T Coy, DH AF Jensen, R. T. Moody, T. W. Ito, T. Coy, D. H. TI Pharmacology of vasoactive intestinal peptide (VIP) and receptor cellular signaling in pancreatic acinar cells SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT C1 NIDDK, NCI, NIH, Bethesda, MD USA. Kyushu Univ, Kyushu, Japan. Tulane Univ, New Orleans, LA 70118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 321 EP 321 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900040 ER PT J AU Eiden, L AF Eiden, Lee TI PACAP signaling: A paradigm for homeostatic response to stress through combinatorial activation of multiple pathways SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT C1 NIMH, Mol Neurosci Sect, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 326 EP 326 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900053 ER PT J AU Gerdin, MJ Eiden, LE AF Gerdin, Matthew J. Eiden, Lee E. TI Combinatorial regulation of Ier3 (PACAP-regulated gene 1) transcription and erk activation by cAMP and calcium SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT C1 NIMH, Mol Neurosci Sect, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 326 EP 327 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900054 ER PT J AU Giladi, E Hill, JM Stack, C Gozes, I AF Giladi, Eliezer Hill, Joanna M. Stack, Conor Gozes, Illana TI VIP regulates the ADNP expression in vivo SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT C1 Tel Aviv Univ, Dept Human Genet & Biochem, IL-69978 Tel Aviv, Israel. NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Neurobiol & Behav, Ithaca, NY 14853 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 329 EP 329 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900060 ER PT J AU Samal, B Eiden, LE AF Samal, Babru Eiden, Lee E. TI Discovering the functional relevance of novel genes captured in microarray screening: Lessons from new PACAP-dependent transcripts of peripheral and central nervous systems SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 8th International Symposium on VIP, PACAP and Related Peptides CY SEP 03-08, 2007 CL Manchester, VT C1 NIMH, NIH, Lab Cellular & Mol Regulat, Mol Neurosci Sect, Bethesda, MD 20892 USA. NIMH, NIH, IRP Bioinformat Core, Bethesda, MD 20892 USA. RI Samal, Babru/C-5563-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 33 IS 3 BP 344 EP 344 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 224HA UT WOS:000250436900099 ER PT J AU Matsuoka, Y Gray, AJ Hirata-Fukae, C Minami, SS Waterhouse, EG Mattson, MP LaFerla, FM Gozes, I Aisen, PS AF Matsuoka, Yasuji Gray, Audrey J. Hirata-Fukae, Chiho Minami, S. Sakura Waterhouse, Emily Graeme Mattson, Mark P. LaFerla, Frank M. Gozes, Illana Aisen, Paul S. TI Intranasal NAP administration reduces accumulation of amyloid peptide and tau hyperphosphorylation in a transgenic mouse model of Alzheimer's disease at early pathological stage SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE Alzheimer's disease; tau; phosphorylation; beta-amyloid peptide; NAP; neuroprotection; intranasal administration; transgenic mouse; therapy ID NEUROPROTECTIVE PROTEIN ADNP; PAIRED HELICAL FILAMENTS; A-BETA; BINDING; PHOSPHORYLATION; MICROTUBULES; SPECIFICITY; ANTIBODIES; INTERACTS; EPITOPES AB Accumulation of P-amyloid (AD) peptide and hyperphosphorylation of tau in the brain are pathological hallmarks of Alzheimer's disease (AD). Agents altering these pathological events might modify clinical disease progression. NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln) is an octapeptide that has shown neuroprotective effects in various in vitro and in vivo neurodegenerative models. Previous studies showed that NAP protected against A beta-induced neurotoxicity, inhibited AD aggregation, and, by binding to tubulin, prevented disruption of micro-tubules. In this study, we investigated the effect of NAP on AD and tau pathology using a transgenic mouse model that recapitulates both aspects of AD. We administered NAP intranasally (0.5 mu g/mouse per day, daily from Monday through Friday) for 3 mo, starting from 9 mo of age, which is a prepathological stage in these mice. NAP treatment significantly lowered levels of A beta 1-40 and 1-42 in brain. In addition, NAP significantly reduced levels of hyperphosphorylated tau. Of particular interest, hyperphosphorylation at the threonine 231 site was reduced; phosphorylation at this site influences microtubule binding. Our results indicate that NAP treatment of transgenic mice initiated at an early stage reduced both A beta and tau pathology, suggesting that NAP might be a potential therapeutic agent for AD. C1 Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Mol Genet & Biochem,Adams Super Ctr Br, Lab Mol Neuroendocrinol,Lily & Avraham Gildor Cha, IL-69978 Tel Aviv, Israel. RP Matsuoka, Y (reprint author), Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. EM ym56@georgetown.edu RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS; NIA NIH HHS [AG022455] NR 34 TC 99 Z9 101 U1 3 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 31 IS 2 BP 165 EP 170 DI 10.1385/JMN/31:02:165 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 144MM UT WOS:000244800300008 PM 17478890 ER PT J AU Hill, JM Hauser, JM Sheppard, LM Abebe, D Spivak-Pohis, I Kushnir, M Deitch, I Gozes, I AF Hill, Joanna M. Hauser, Janet M. Sheppard, Lia M. Abebe, Daniel Spivak-Pohis, Irit Kushnir, Michal Deitch, Iris Gozes, Illana TI Blockage of VIP during mouse embryogenesis modifies adult behavior and results in permanent changes in brain chemistry SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Review DE anxiety-like behavior; social behavior; activity-dependent neuroprotective protein (ADNP); autism; neuronal survival; synaptogenesis; neurodevelopmental disorders ID VASOACTIVE-INTESTINAL-PEPTIDE; DEPENDENT NEUROPROTECTIVE PROTEIN; FETAL ALCOHOL SYNDROME; EYE-MOVEMENT SLEEP; EMBRYONIC GROWTH; DOWN-SYNDROME; NEUROTROPHIC FACTOR; DEFICIENT MICE; VALPROIC ACID; FUNCTIONAL EXPRESSION AB Vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis. Blockage of VIP with a VIP antagonist during this period results in growth restriction, microcephaly, and developmental delays. Similar treatment of neonatal rodents also causes developmental delays and impaired diurnal rhythms, and the adult brains of these animals exhibit neuronal dystrophy and increased VIP binding. These data suggest that blockage of VIP during the development of the nervous system can result in permanent changes to the brain. In the current study, pregnant mice were treated with a VIP antagonist during embryonic days 8 through 10. The adult male offspring were examined in tests of novelty, paired activity, and social recognition. Brain tissue was examined for several measures of chemistry and gene expression of VIP and related compounds. Glial cells from the cortex of treated newborn mice were plated with neurons and examined for VIP binding and their ability to enhance neuronal survival. Treated adult male mice exhibited increased anxiety-like behavior and deficits in social behavior. Brain tissue exhibited regionally specific changes in VIP chemistry and a trend toward increased gene expression of VIP and related compounds that reached statistical significance in the VIP receptor, VPAC-1, in the female cortex. When compared to control astrocytes, astrocytes from treated cerebral cortex produced further increases in neuronal survival with excess synaptic connections and reduced VIP binding. In conclusion, impaired VIP activity during mouse embryogenesis resulted in permanent changes to both adult brain chemistry/cell biology and behavior with aspects of autism-like social deficits. C1 Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. NICHD, Lab Dev Neurosci, NIH, Bethesda, MD 21029 USA. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. EM igozes@post.tau.ac.il FU Intramural NIH HHS NR 107 TC 18 Z9 18 U1 4 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2007 VL 31 IS 3 BP 183 EP 200 DI 10.1385/JMN/31:03:183 PG 18 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 169JP UT WOS:000246588800001 PM 17726225 ER PT J AU Blanco, I de Serres, F Janciauskiene, S Arbesu, D Fernandez-Bustillo, E Carcaba, V Nita, I Astudillo, A AF Blanco, Ignacio de Serres, Frederick Janciauskiene, Sabina Arbesu, Daniel Fernandez-Bustillo, Enrique Carcaba, Victoriano Nita, Izabela Astudillo, Aurora TI Estimates of the prevalence and number of Fibromyalgia syndrome patients and their alpha-1 antitrypsin phenotypic distribution in ten countries SO JOURNAL OF MUSCULOSKELETAL PAIN LA English DT Review DE fibromyalgia syndrome; fibromyalgia syndrome prevalence; alpha-1 antitrypsin deficiency; epidemiological studies ID OBSTRUCTIVE PULMONARY-DISEASE; PI PHENOTYPES; ALPHA(1)-ANTITRYPSIN DEFICIENCY; RHEUMATIC-DISEASES; GENERAL-POPULATION; ALPHA-ANTITRYPSIN; MUSCULOSKELETAL DISEASES; FINNISH POPULATION; LUNG-FUNCTION; SERUM AB Objectives: During the last few years, clinical, epidemiological, and pathological evidence has suggested that inherited alpha-1 antitrypsin [AAT] deficiency might play a role in the development of the fibromyalgia syndrome [FMS], probably because of the loss of AAT anti-inflammatory efficacy. The objective of this study was to estimate the prevalence and number of FMS patients, and their AAT phenotypic distribution worldwide. Methods: A critical review selecting reliable studies on the subject. Results: Studies on AAT gene frequencies and FMS prevalence were retrieved for ten countries worldwide, namely Canada, the United States of America [USA], Denmark, Finland, Germany, Italy, the Netherlands, Spain, Sweden, and Pakistan. The severe deficiency Z allele was found in all these countries, with very high frequencies in Denmark and Sweden [23 and 27 per 1,000, respectively], high frequencies in Italy and Spain [16 and 17], intermediate frequencies in Germany, the Netherlands, Canada, and the USA [10 to 14], and a low frequency in Pakistan [nine per 1,000]. The calculated prevalence of AAT deficiency and the number of FMS patients with AAT deficiency were 1/10 and 25,408 in Canada, 1/11 and 478,681 in the US, 1/9 and 3,124 in Denmark, 1/36 and 726 in Finland, 1/16 and 48,523 in Germany, 1/13 and 84,876 in Italy, 1115 and 9,639 in the Netherlands, 1/4 and 114,359 in Spain, 1/11 and 9,065 in Sweden, and 1/25 and 85.965 in Pakistan. Our calculations predict that AAT deficiency would remain undetected in around nine percent of FMS patients, with about eight percent of them carrying moderate deficiency phenotypes [MS, SS, and MZ], and less than one percent with severe deficiency phenotypes [SZ and ZZ]. Conclusions: Therefore, AAT phenotype characterization should be recommended in FMS patients and the possible efficacy of AAT replacement therapy in severe deficiency FMS patients should warrant further Studies. C1 Hosp Valle Nalon, Dept Internal Med, Sama De Langreo 33920, Principado Astu, Spain. NIEHS, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Malmo Univ Hosp, Dept Clin Sci, S-20502 Malmo, Sweden. Hosp Valle Nalon, Dept Rehabil Med, Sama De Langreo 33920, Principado De A, Spain. Hosp Univ Cent Asturias, Biostat Unit, Oviedo, Principado De A, Spain. Hosp Univ Cent Asturias, Dept Pathol, Oviedo, Principado De A, Spain. RP Blanco, I (reprint author), Hosp Valle Nalon, Dept Internal Med, Sama De Langreo 33920, Principado Astu, Spain. EM ignacio.blanco@sespa.princast.es NR 104 TC 3 Z9 3 U1 0 U2 4 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1058-2452 J9 J MUSCULOSKELET PAIN JI J. Musculoskelet. Pain PY 2007 VL 15 IS 4 BP 9 EP 23 DI 10.1300/J094v15n04_03 PG 15 WC Rehabilitation; Rheumatology SC Rehabilitation; Rheumatology GA 205SY UT WOS:000249136100003 ER PT J AU Agnati, LF Genedani, S Leo, G Forni, A Woods, AS Filaferro, M Franco, R Fuxe, K AF Agnati, L. F. Genedani, S. Leo, G. Forni, A. Woods, A. S. Filaferro, M. Franco, R. Fuxe, K. TI A beta peptides as one of the crucial volume transmission signals in the trophic units and their interactions with homocysteine. Physiological implications and relevance for Alzheimer's disease SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE beta-amyloid peptides; homocysteine; volume transmission; pain threshold; Alzheimer's disease ID CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA; PLASMA HOMOCYSTEINE; PARKINSONS-DISEASE; PRECURSOR PROTEIN; NEURODEGENERATION; NEUROTOXICITY; NOCICEPTION; AGGREGATION; RECEPTOR AB Amyloid peptides (A beta) can operate as volume transmission (VT) signals since they are continuously released from cells of the central nervous system and diffuse in the extra-cellular space of the brain. They have both regulatory and trophic functions on cellular networks. In agreement with A beta regulatory actions on glial-neuronal networks, the present paper reports new findings demonstrating that intrastriatal injections of A beta peptides reduce striatal tyrosine hydroxylase, increase striatal GFAP immunoreactivities and lower pain threshold in experimental rats. Furthermore, it has been demonstrated that exogenous homocysteine (Hcy) binds A beta(1-40) favouring its beta-sheet conformation both in vitro and in vivo and hence the formation of beta-fibrils and development of neurotoxicity. Thus, the hypothesis is discussed that A beta peptides represent crucial VT-signals in the brain and their action is altered by dysmetabolic signals such as high Hcy extra-cellular levels, known to be an important risk factor for Alzheimer's disease. C1 Univ Modena & Reggio Emilia, Physiol Sect, Dept Biomed Sci, I-41100 Modena, Italy. Univ Modena & Reggio Emilia, Pharmacol Sect, Dept Biomed Sci, I-41100 Modena, Italy. Univ Modena & Reggio Emilia, Dept Chem, I-41100 Modena, Italy. IRCCS San Camillo, Venice, Italy. Natl Inst Drug Abuse, Dept Hlth & Human Serv, Baltimore, MD USA. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Agnati, LF (reprint author), Univ Modena & Reggio Emilia, Physiol Sect, Dept Biomed Sci, Via Campi 287, I-41100 Modena, Italy. EM luigiagnati@tin.it RI Franco, Rafael/C-3694-2015; Genedani, Susanna/K-4370-2016; OI Franco, Rafael/0000-0003-2549-4919; Genedani, Susanna/0000-0003-1526-153X; Fuxe, Kjell/0000-0001-8491-4288 NR 48 TC 26 Z9 27 U1 0 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD JAN PY 2007 VL 114 IS 1 BP 21 EP 31 DI 10.1007/s00702-006-0564-9 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 119XO UT WOS:000243048000003 PM 16969627 ER PT J AU Fuxe, K Canals, M Torvinen, M Marcellino, D Terasmaa, A Genedani, S Leo, G Guidolin, D Diaz-Cabiale, Z Rivera, A Lundstrom, L Langel, U Narvaez, J Tanganelli, S Lluis, C Ferre, S Woods, A Franco, R Agnati, LF AF Fuxe, K. Canals, M. Torvinen, M. Marcellino, D. Terasmaa, A. Genedani, S. Leo, G. Guidolin, D. Diaz-Cabiale, Z. Rivera, A. Lundstrom, L. Langel, U. Narvaez, J. Tanganelli, S. Lluis, C. Ferre, S. Woods, A. Franco, R. Agnati, L. F. TI Intramembrane receptor-receptor interactions: a novel principle in molecular medicine SO JOURNAL OF NEURAL TRANSMISSION LA English DT Review DE A2A receptors; D2-like receptors; metabotropic glutamate receptor 5; neuropeptide receptors; receptor heteromers; receptor mosaics; basal ganglia; novel treatment strategies in neuropsychopharmacology; learning and memory ID ADENOSINE A(2A) RECEPTOR; CENTRAL-NERVOUS-SYSTEM; C-FOS EXPRESSION; HEPTASPANNING MEMBRANE-RECEPTORS; METABOTROPIC GLUTAMATE RECEPTORS; BIOLUMINESCENCE ENERGY-TRANSFER; ANGIOTENSIN-II RESPONSIVENESS; BETA-ADRENERGIC RECEPTORS; DOPAMINE D2 RECEPTORS; VENTRAL LIMBIC CORTEX AB In 1980/81 Agnati and Fuxe introduced the concept of intramembrane receptor-receptor interactions and presented the first experimental observations for their existence in crude membrane preparations. The second step was their introduction of the receptor mosaic hypothesis of the engram in 1982. The third step was their proposal that the existence of intramembrane receptor-receptor interactions made possible the integration of synaptic (WT) and extrasynaptic (VT) signals. With the discovery of the intramembrane receptor-receptor interactions with the likely formation of receptor aggregates of multiple receptors, so called receptor mosaics, the entire decoding process becomes a branched process already at the receptor level in the surface membrane. Recent developments indicate the relevance of cooperativity in intramembrane receptor-receptor interactions namely the presence of regulated cooperativity via receptor-receptor interactions in receptor mosaics (RM) built up of the same type of receptor (homo-oligomers) or of subtypes of the same receptor (RM type1). The receptor-receptor interactions will to a large extent determine the various conformational states of the receptors and their operation will be dependent on the receptor composition (stoichiometry), the spatial organization (topography) and order of receptor activation in the RM. The biochemical and functional integrative implications of the receptor-receptor interactions are outlined and long-lived heteromeric receptor complexes with frozen RM in various nerve cell systems may play an essential role in learning, memory and retrieval processes. Intramembrane receptor-receptor interactions in the brain have given rise to novel strategies for treatment of Parkinson's disease (A2A and mGluR5 receptor antagonists), schizophrenia (A2A and mGluR5 agonists) and depression (galanin receptor antagonists). The A2A/D2, A2A/D3 and A2A/mGluR5 heteromers and heteromeric complexes with their possible participation in different types of RM are described in detail, especially in the cortico-striatal glutamate synapse and its extrasynaptic components, together with a postulated existence of A2A/D4 heteromers. Finally, the impact of intramembrane receptor-receptor interactions in molecular medicine is discussed outside the brain with focus on the endocrine, the cardiovascular and the immune systems. C1 Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, S-17177 Stockholm, Sweden. Univ Modena & Reggio Emilia, Dept Biomed Sci, Modena, Italy. IRCCS, Venice, Italy. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. Univ Malaga, Fac Med, Dept Physiol, E-29071 Malaga, Spain. Univ Malaga, Sch Sci, Dept Cell Biol, E-29071 Malaga, Spain. Univ Stockholm, Dept Neurochem, Stockholm, Sweden. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. Natl Inst Drug Abuse, IRP, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. Univ Padua, Dept Anat & Human Physiol, Padua, Italy. RP Fuxe, K (reprint author), Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, S-17177 Stockholm, Sweden. EM Kjell.Fuxe@ki.se RI Ferre, Sergi/K-6115-2014; Rivera, Alicia/L-2098-2014; Franco, Rafael/C-3694-2015; Terasmaa, Anton/I-3312-2015; Tanganelli, Sergio/I-7704-2015; Genedani, Susanna/K-4370-2016; OI Fuxe, Kjell/0000-0001-8491-4288; Narvaez, Jose A./0000-0002-3575-6903; Canals, Meritxell/0000-0002-7942-5006; Guidolin, Diego/0000-0003-2133-3552; Diaz Cabiale, Maria Zaida/0000-0003-4613-9430; Ferre, Sergi/0000-0002-1747-1779; Rivera, Alicia/0000-0002-7282-0441; Franco, Rafael/0000-0003-2549-4919; Terasmaa, Anton/0000-0002-5139-1764; Tanganelli, Sergio/0000-0001-7576-3510; Genedani, Susanna/0000-0003-1526-153X; Diaz-Cabiale, Zaida/0000-0002-1582-2088; Marcellino, Daniel/0000-0002-4618-7267 NR 198 TC 82 Z9 83 U1 0 U2 7 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD JAN PY 2007 VL 114 IS 1 BP 49 EP 75 DI 10.1007/s00702-006-0589-0 PG 27 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 119XO UT WOS:000243048000006 PM 17066251 ER PT J AU Franco, R Lluis, C Canela, EI Mallol, J Agnati, L Casado, V Ciruela, F Ferre, S Fuxe, K AF Franco, R. Lluis, C. Canela, E. I. Mallol, J. Agnati, L. Casado, V. Ciruela, F. Ferre, S. Fuxe, K. TI Receptor-receptor interactions involving adenosine A(1) or dopamine D(1) receptors and accessory proteins SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE adenosine deaminase; hsc73; clustering parkinson; caveolin ID COTRANSFECTED FIBROBLAST CELLS; RAT CEREBRAL-CORTEX; BASAL GANGLIA; NUCLEUS-ACCUMBENS; A(2A) RECEPTORS; SYNERGISTIC INTERACTION; HEPTAHELICAL RECEPTORS; MEDIATED MODULATION; MULTIPLE LEVELS; SF9 CELLS AB The molecular basis for the known intramembrane receptor-receptor interactions among heptahelical receptors (G protein coupled receptors, GPCR) was postulated to be heteromerization based on receptor subtype specific interactions between different types of homomers of GPCR. Adenosine and dopamine receptors in the basal ganglia have been fundamental to demonstrate the existence of receptor heteromers and the functional consequences of such molecular interactions. The heterodimer is only one type of heteromeric complex and the evidence is equally compatible with the existence of higher order heteromeric complexes, where also adapter proteins such as homer proteins and scaffolding proteins can exist, assisting in the process of linking the GPCR and ion channel receptors together in a receptor mosaic that may have special integrative value and may constitute the molecular basis for learning and memory. Heteromerization of D(2) dopamine and A(2A) adenosine receptors is reviewed by Fuxe in another article in this special issue. Here, heteromerization between D(1) dopamine and A(1) adenosine receptors is reviewed. Heteromers formed by dopamine D(1) and D(2) receptors and by adenosine A(1) and A(2A) receptors also occur in striatal cells and open new perspectives to understand why two receptors with apparently opposite effects are expressed in the same neuron and in the nerve terminals. The role of accessory proteins also capable of interacting with receptor-receptor heteromers in regulating the traffic and the molecular physiology of these receptors is also discussed. Overall, the knowledge of the reason why such complex networks of receptor-receptor and receptor-protein interactions occur in striatal cells is crucial to develop new strategies to combat neurological and neuropsychiatric diseases. C1 Univ Barcelona, Dept Biochem & Mol Biol, Mol Neurobiol Unit, IDIBAPS, E-08028 Barcelona, Spain. Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy. Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Franco, R (reprint author), Univ Barcelona, Dept Biochem & Mol Biol, Mol Neurobiol Unit, IDIBAPS, Marti Franques 1, E-08028 Barcelona, Spain. EM rfranco@ub.edu RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825 NR 76 TC 37 Z9 38 U1 0 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD JAN PY 2007 VL 114 IS 1 BP 93 EP 104 DI 10.1007/s00702-006-0566-7 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 119XO UT WOS:000243048000008 PM 17024327 ER PT J AU Doolittle, ND Peereboom, DM Christoforidis, GA Hall, WA Palmieri, D Brock, PR Campbell, K Dickey, DT Muldoon, LL O'Neill, BP Peterson, DR Pollock, B Soussain, C Smith, Q Tyson, RM Neuwelt, EA AF Doolittle, Nancy D. Peereboom, David M. Christoforidis, Gregory A. Hall, Walter A. Palmieri, Diane Brock, Penelope R. Campbell, Kathleen Dickey, D. Thomas Muldoon, Leslie L. O'Neill, Brian Patrick Peterson, Darryl R. Pollock, Brad Soussain, Carole Smith, Quentin Tyson, Rose Marie Neuwelt, Edward A. TI Delivery of chemotherapy and antibodies across the blood-brain barrier and the role of chemoprotection, in primary and metastatic brain tumors: report of the eleventh annual blood-brain barrier consortium meeting SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE blood-brain barrier; brain delivery; brain metastases; brain tumors; chemoprotection ID CENTRAL-NERVOUS-SYSTEM; CISPLATIN-INDUCED OTOTOXICITY; INDUCED HEARING-LOSS; CELL LUNG-CANCER; BREAST-CANCER; D-METHIONINE; SODIUM THIOSULFATE; N-ACETYLCYSTEINE; CHILDHOOD HEPATOBLASTOMA; INDIVIDUAL SENSITIVITY AB Although knowledge of molecular biology and cellular physiology has advanced at a rapid pace, much remains to be learned about delivering chemotherapy and antibodies across the blood-brain barrier (BBB) for the diagnosis and treatment of central nervous system (CNS) disease. A meeting, partially funded by an NIH R13 grant, was convened to discuss the state of the science, current knowledge gaps, and future directions in the delivery of drugs and proteins to the CNS, for the treatment of primary and metastatic brain tumors. Meeting topics included CNS metastases and the BBB, and chemoprotection and chemoenhancement in CNS disorders. The discussions regarding CNS metastases generated possibilities of chemoprotection as a means not only to decrease treatment-related toxicity but also to increase chemotherapy dose intensity. The increasing incidence of sanctuary brain metastasis from breast cancer, in part due to the difficulty of monoclonal antibodies (mAbs) such as herceptin to cross the BBB, was one of the most salient "take home" messages of the meeting. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Cleveland Clin Fdn, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. Ohio State Univ, Med Ctr, Dept Radiol, Columbus, OH 43210 USA. Univ Minnesota, Dept Neurosurg, Minneapolis, MN 55455 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NHS Trust, London, England. Great Ormond St Hosp Sick Children, UCLH NHS Trust, Middlesex Hosp, London WC1N 3JH, England. So Illinois Univ, Sch Med, Springfield, IL 62794 USA. Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. Finch Univ Hlth Sci Chicago Med Sch, Dept Physiol & Biophys, N Chicago, IL 60064 USA. Univ Texas San Antonio, San Antonio, TX 78229 USA. Texas Tech, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu RI Palmieri, Diane/B-4258-2015 FU NCI NIH HHS [R13 CA 86959-05] NR 58 TC 24 Z9 27 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2007 VL 81 IS 1 BP 81 EP 91 DI 10.1007/s11060-006-9209-y PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 118VC UT WOS:000242970100012 PM 16858513 ER EF