FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Yang, DF Stewart, TJ Smith, KK Georgi, D Abrams, SI Liu, KB AF Yang, Dafeng Stewart, Trina J. Smith, Kimberly K. Georgi, David Abrams, Scott I. Liu, Kebin TI Downregulation of IFN-gamma R in association with loss of Fas function is linked to tumor progression SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE IFN-gamma R; Fas; immunoselection; tumor progression; tumor escape ID COLON-CARCINOMA CELLS; CTL ADOPTIVE IMMUNOTHERAPY; ANTIGEN-LOSS VARIANTS; CD8(+) T-CELLS; INTERFERON-GAMMA; IN-VIVO; METASTATIC MELANOMA; MEDIATED APOPTOSIS; INFILTRATING LYMPHOCYTES; IMMUNOCOMPETENT MICE AB work in the recognition and destruction of tumor cells, and it has been demonstrated that lymphocytes and IFN-gamma are the primary tumor suppressors of the immune system. However, the immune system can concurrently select for tumor variants with reduced immunogenicity and aggressive phenotypes. We report here that tumor escape variants that have survived CTL adoptive immunotherapy exhibited decreased expression levels of both Fas and IFN-gamma R in vitro. Furthermore, examination of spontaneously arising mouse primary mammary carcinoma and lung metastases revealed that both Fas and IFN-gamma R protein levels were dramatically lower in lung metastases than in primary tumors in vivo. Functional disruption of either the Fas- or the IFN-gamma signaling pathway enhanced the colonization efficiency of preexisting metastatic tumor cells, whereas disruption of both Fas and IFN-gamma R pathways resulted in synergistic augmentation of the colonization efficiency of the preexisting metastatic tumor cells, as determined by experimental lung metastases assay. Gene expression profiling revealed that altered expression of genes involved in immediate IFN-gamma R signaling, the interferon primary response, apoptosis and tumor colonization is associated with loss of IFN-gamma R function and enhanced metastatic potential. Interestingly, disruption of IFN-gamma R function did not alter tumor cell susceptibility to CTL-mediated cytotoxicity, but is linked to enhanced infiltration of endogenous T cells in the tumor microenvironment in vivo. These findings suggest that coordinate downregulation of Fas and IFN-gamma R, 2 key components of cancer immunosurveillance system on tumor cells, leads to a more aggressive metastatic phenotype. (C) 2007 Wiley-Liss, Inc. C1 [Yang, Dafeng; Liu, Kebin] Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. [Stewart, Trina J.; Abrams, Scott I.] NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. [Smith, Kimberly K.; Georgi, David] Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA. RP Liu, KB (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, 1459 Laney Walker Blvd, Augusta, GA 30912 USA. EM Kliu@mcg.edu RI Stewart, Trina/F-5967-2012; OI Stewart, Trina/0000-0003-3220-9231; Liu, Kebin/0000-0003-1965-7240 FU Intramural NIH HHS NR 67 TC 20 Z9 21 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 15 PY 2008 VL 122 IS 2 BP 350 EP 362 DI 10.1002/ijc.23090 PG 13 WC Oncology SC Oncology GA 242DJ UT WOS:000251704400013 PM 17918178 ER PT J AU Diwakar, G Zhang, DM Jiang, SL Hornyak, TJ AF Diwakar, Ganesh Zhang, Deming Jiang, Shunlin Hornyak, Thomas J. TI Neurofibromin as a regulator of melanocyte development and differentiation SO JOURNAL OF CELL SCIENCE LA English DT Article DE neurofibromin; melanocyte; development ID RECEPTOR TYROSINE KINASE; AU-LAIT MACULES; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; MAST-CELLS; NF1 GENE; TYPE-1 NEUROFIBROMATOSIS; DOPACHROME TAUTOMERASE; BENIGN NEUROFIBROMAS; IN-VIVO; PROTEIN AB Patients with the genetic disease type I neurofibromatosis (NF1) exhibit characteristic pigmentary lesions associated with loss of a single allele of NF1, encoding the 260 kDa protein neurofibromin. To understand the basis for these pigmentary problems, the properties of melanocytes haploinsufficient for the murine gene Nf1 were studied using Nf1(+/-) knockout mice. We demonstrate that neurofibromin regulates the Kit-Mitf signaling axis in vivo during melanocyte development. Primary Nf1(+/-) melanocytes were purified by FACS to measure melanogenic gene expression. We found that Nf1(+/-) melanocytes exhibit higher levels of melanogenic gene expression than their wild-type counterparts. Both prior to and following Kit stimulation, Nf1(+/-) melanocytes also exhibit increased activation of the MAP kinase pathway compared with primary cells. The melanogenic response of primary melanocytes to Mek inhibition is consistent with the changes observed with Nf1 haploinsufficiency; however, these changes differ from those observed with their immortalized counterparts. The observation that reduction of neurofibromin, either from haploinsufficiency in the case of primary melanocytes or from neurofibromin knockdown in the case of melan-a cells, enhances melanogenic gene expression suggests that neurofibromin plays a dominant role to MEK activity in controlling melanogenic gene expression in murine melanocytes. C1 [Diwakar, Ganesh; Zhang, Deming; Jiang, Shunlin; Hornyak, Thomas J.] NCI, Dermatol Branch, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hornyak, TJ (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Natl Inst Hlth, 10 Ctr Dr, Bethesda, MD 20892 USA. EM hornyakt@mail.nih.gov FU Intramural NIH HHS; NIAMS NIH HHS [R01 AR47951] NR 59 TC 18 Z9 18 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN 15 PY 2008 VL 121 IS 2 BP 167 EP 177 DI 10.1242/jcs.013912 PG 11 WC Cell Biology SC Cell Biology GA 249QJ UT WOS:000252243600007 PM 18089649 ER PT J AU Sohn, HW Pierce, SK Tzeng, SJ AF Sohn, Hae Won Pierce, Susan K. Tzeng, Shiang-Jong TI Live cell imaging reveals that the inhibitory Fc gamma RIIB destabilizes B cell receptor membrane-lipid blocks immune synapse formation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESONANCE ENERGY-TRANSFER; ANTIGEN RECEPTOR; LIVING CELLS; RAFTS; INITIATION; TRANSLOCATION; POLYMORPHISM; AFFINITY; DISEASE; STEP AB The Fc gamma RIIB is a potent regulator of BCR signaling and as such plays a decisive role in controlling autoimmunity. The use of advanced imaging technologies has provided evidence that the earliest events in Ag-induced BCR signaling include the clustering of the BCR, the selective and transient association of the clustered BCR with raft lipids, and the concentration of BCR clusters in an immune synapse. That lipid rafts play a role in Fc gamma RIIB's regulation of BCR signaling was suggested by recent studies showing that a lupus-associated loss of function mutation resulted in the receptor's exclusion from lipid rafts and the failure to regulate BCR signaling. In this study, we provide evidence from both biochemical analyses and fluorescence resonance energy transfer in conjunction with both confocal and total internal reflection microscopy in living cells that the Fc gamma RIIB, when coligated with the BCR, associates with lipid rafts and functions both to destabilize the association of the BCR with raft lipids and to block the subsequent formation of the B cell's immune synapse. These results define new early targets of Fc gamma RIIB inhibitory activity in the Ag-induced B cell activation pathway. C1 [Sohn, Hae Won; Pierce, Susan K.; Tzeng, Shiang-Jong] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Tzeng, SJ (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 213, Rockville, MD 20852 USA. EM sjtzeng@niaid.nih.gov FU Intramural NIH HHS NR 26 TC 31 Z9 38 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 15 PY 2008 VL 180 IS 2 BP 793 EP 799 PG 7 WC Immunology SC Immunology GA 250HG UT WOS:000252290000014 PM 18178817 ER PT J AU Rankin, AL Reed, AJ Oh, S Picca, CC Guay, HM Larkin, J Panarey, L Aitken, MK Koeberlein, B Lipsky, PE Tomaszewski, JE Naji, A Caton, AJ AF Rankin, Andrew L. Reed, Amy J. Oh, Soyoung Picca, Cristina Cozzo Guay, Heath M. Larkin, Joseph, III Panarey, Laura Aitken, Malinda K. Koeberlein, Brigitte Lipsky, Peter E. Tomaszewski, John E. Naji, Ali Caton, Andrew J. TI CD4(+) T cells recognizing a single self-peptide expressed by APCs induce spontaneous autoimmune arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; TRANSGENIC MICE; HOMEOSTATIC EXPANSION; SYNOVIAL INFLAMMATION; FUNCTIONAL IMPAIRMENT; THYMIC SELECTION; POSITIVE CELLS; LYMPH-NODES; IN-VITRO AB We have examined processes leading to the spontaneous development of autoimmune inflammatory arthritis in transgenic mice containing CD4(+) T cells targeted to a nominal Ag (hemagglutinin (HA)) and coexpressing HA driven by a MHC class II promoter. Despite being subjected to multiple tolerance mechanisms, autoreactive CD4(+) T cells accumulate in the periphery of these mice and promote systemic proinflammatory cytokine production. The majority of mice spontaneously develop inflammatory arthritis, which is accompanied by an enhanced regional immune response in lymph nodes draining major joints. Arthritis development is accompanied by systemic B cell activation; however, neither B cells nor Ab is required for arthritis development, since disease develops in a B cell-deficient background. Moreover, arthritis also develops in a recombinase activating gene-deficient background, indicating that the disease process is driven by CD4(+) T cells recognizing the neo-self HA Ag. These findings show that autoreactive CD4(+) T cells recognizing a single self-Ag, expressed by systemically distributed APCs, can induce arthritis via a mechanism that is independent of their ability to provide help for autoantibody production. C1 [Rankin, Andrew L.; Reed, Amy J.; Oh, Soyoung; Picca, Cristina Cozzo; Guay, Heath M.; Larkin, Joseph, III; Panarey, Laura; Aitken, Malinda K.; Caton, Andrew J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Reed, Amy J.; Koeberlein, Brigitte; Naji, Ali] Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA. [Tomaszewski, John E.] Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. [Tomaszewski, John E.] Univ Penn, Med Ctr, Lab Med, Philadelphia, PA 19104 USA. [Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Caton, AJ (reprint author), Wistar Inst Anat & Biol, Room 262,3601 Spruce St, Philadelphia, PA 19104 USA. EM caton@wistar.org RI Larkin, Joseph/H-2990-2012 FU NIAID NIH HHS [T32 AI055428] NR 48 TC 21 Z9 21 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 15 PY 2008 VL 180 IS 2 BP 833 EP 841 PG 9 WC Immunology SC Immunology GA 250HG UT WOS:000252290000019 PM 18178822 ER PT J AU Foulds, KE Rotte, MJ Paley, MA Singh, B Douek, DC Hill, BJ O'Shea, JJ Watford, WT Seder, RA Wu, CY AF Foulds, Kathryn E. Rotte, Masashi J. Paley, Michael A. Singh, Babu Douek, Daniel C. Hill, Brenna J. O'Shea, John J. Watford, Wendy T. Seder, Robert A. Wu, Chang-You TI IFN-gamma mediates the death of Th1 cells in a paracrine manner SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-BETA CHAIN; CD4 T-CELLS; INTERFERON-GAMMA; T(H)1 CELLS; INDOLEAMINE 2,3-DIOXYGENASE; DENDRITIC CELLS; IN-VIVO; EXPRESSION; MEMORY; MICE AB Th1 cells have different capacities to develop into memory cells based on their production of IFN-gamma. In this study, the mechanism by which a homogenous population of IFN-gamma-producing CD4 T cells was eliminated in vivo was assessed. When such cells were transferred into naive mice and activated with Ag, a striking decrease in the frequency of cells in the spleen and lung was observed. However, administration of neutralizing anti-IFN-gamma Ab at the time of Ag challenge largely prevented the elimination of such cells. To determine whether IFN-gamma was mediating its effects directly and/or indirectly, the ability of IFN-gamma to effectively signal in such cells was assessed in vitro. Indeed, there was reduced phosphorylation of STAT1 in response to IFN-gamma as well as markedly reduced expression of the IFN-gamma R beta-chain. Furthermore, transfer of such cells into IFN-gamma R-deficient mice limited their death following activation with Ag. Together, these data suggest that IFN-gamma acts in a paracrine manner to mediate the death of activated IFN-gamma-producing Th1 cells. In contrast to Ag stimulation, administration of CpG alone resulted in the elimination of Th1 cells in IFN-gamma R(-/-) mice. These results show that in response to Ag stimulation, the death of IFN-gamma-producing effector Th1 cells is controlled in an IFN-gamma-dependent manner, whereas in response to innate activation, the death of IFN-gamma-producing Th1 cells can occur through an IFN-gamma-independent pathway. Collectively, these data show the multiple mechanisms by which Th1 effector cells are efficiently eliminated in vivo. C1 [Foulds, Kathryn E.; Rotte, Masashi J.; Paley, Michael A.; Singh, Babu; Seder, Robert A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Douek, Daniel C.; Hill, Brenna J.] NIAID, Human Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [O'Shea, John J.; Watford, Wendy T.] NIAMSD, Mol Immunol Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Wu, Chang-You] Zhongshan Med Sch Univ, Dept Immunol, Guangzhou, Peoples R China. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 3512, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov NR 32 TC 21 Z9 22 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2008 VL 180 IS 2 BP 842 EP 849 PG 8 WC Immunology SC Immunology GA 250HG UT WOS:000252290000020 PM 18178823 ER PT J AU Souto-Carneiro, MM Fritsch, R Sepulveda, N Lagareiro, MJ Morgado, N Longo, NS Lipsky, PE AF Souto-Carneiro, M. Margarida Fritsch, Ruth Sepulveda, Nuno Lagareiro, M. Joao Morgado, Nuno Longo, Nancy S. Lipsky, Peter E. TI The NF-kappa B canonical pathway is involved in the control of the exnucleolytic processing of coding ends during V(D)J recombination SO JOURNAL OF IMMUNOLOGY LA English DT Article ID C-H TRANSCRIPTION; ANHIDROTIC ECTODERMAL DYSPLASIA; CELL TERMINAL DIFFERENTIATION; PROLIFERATIVE RESPONSES; SIGNALING PATHWAYS; SELECTIVE DEFECTS; IMMUNE-RESPONSES; HUMAN-DISEASE; RAG PROTEINS; CHAIN CDR3 AB V(D)J recombination is essential to produce an Ig repertoire with a large range of Ag specificities. Although NF-kappa B-binding sites are present in the human and mouse IgH, Ig kappa, and Ig lambda enhancer modules and RAG expression is controlled by NF-kappa B, it is not known whether NF-kappa B regulates V(D)J recombination mechanisms after RAG-mediated dsDNA breaks. To clarify the involvement of NF-kappa B in human V(D)J recombination, we amplified Ig gene rearrangements from individual peripheral B cells of patients with X-linked anhidrotic ectodermal dysplasia with hyper-IgM syndrome (HED-ID) who have deficient expression of the NF-kappa B essential modulator (NEMO/Ikk gamma). The amplification of nonproductive Ig gene rearrangements from HED-ID) B cells reflects the influence of the Ikky-mediated canonical NF-kappa B pathway on specific molecular mechanisms involved in V(D)J recombination. We found that the CDR3(H), from HED-ID B cells were abnormally long, as a result of a marked reduction in the exonuclease activity on the V, D, and J germline coding ends, whereas random N-nucleotide addition and palindromic overhangs (P nucleotides) were comparable to controls. This suggests that an intact canonical NF-kappa B pathway is essential for normal exonucleolytic activity during human V(D)J recombination, whereas terminal deoxynucleotide transferase, Artemis, and DNA-dependent protein kinase catalytic subunit activity are not affected. The generation of memory B cells and somatic hypermutation were markedly deficient confirming a role for NF-kappa B in these events of B cell maturation. However, selection of the primary B cell repertoire appeared to be intact and was partially able to correct the defects generated by abnormal V(D)J recombination. C1 [Souto-Carneiro, M. Margarida; Fritsch, Ruth; Longo, Nancy S.; Lipsky, Peter E.] NIAMSD, Natl Inst Hlth, Autoimmun Branch, Bethesda, MD 20892 USA. [Souto-Carneiro, M. Margarida; Sepulveda, Nuno; Lagareiro, M. Joao; Morgado, Nuno] Gulbenkian Inst Sci, Oeiras, Portugal. [Fritsch, Ruth] Med Univ Vienna, Vienna, Austria. [Sepulveda, Nuno] Univ Lisbon, Ctr Stat & Applicat, P-1699 Lisbon, Portugal. RP Lipsky, PE (reprint author), NIAMSD, Natl Inst Hlth, Autoimmun Branch, Room 6D47C,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov RI Fritsch-sTork, Ruth/G-9702-2012; Souto-Carneiro, Margarida/C-4386-2016 OI Souto-Carneiro, Margarida/0000-0001-6923-0590 FU Intramural NIH HHS NR 68 TC 6 Z9 6 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 15 PY 2008 VL 180 IS 2 BP 1040 EP 1049 PG 10 WC Immunology SC Immunology GA 250HG UT WOS:000252290000041 PM 18178844 ER PT J AU Belogurov, AA Kurkova, IN Friboulet, A Thomas, D Misikov, VK Zakharova, MY Suchkov, SV Kotov, SV Alehin, AI Avalle, B Souslova, EA Morse, HC Gabibov, AG Pononlarenko, NA AF Belogurov, Alexey A., Jr. Kurkova, Inna N. Friboulet, Alain Thomas, Daniel Misikov, Viktor K. Zakharova, Maria Yu. Suchkov, Sergey V. Kotov, Sergey V. Alehin, Alexander I. Avalle, Berangere Souslova, Ekaterina A. Morse, Herbert C., III Gabibov, Alexander G. Pononlarenko, Natalia A. TI Recognition and degradation of myelin basic protein peptides by serum autoantibodies: Novel biomarker for multiple sclerosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DNA-HYDROLYZING AUTOANTIBODIES; ANTIMYELIN ANTIBODIES; CATALYTIC ANTIBODIES; IMMUNODOMINANT EPITOPE; DISEASE; CLEAVAGE; ANTIGEN; MRI; SUSCEPTIBILITY; DEIMINATION AB The pathologic role of autoantibodies in autoimmune disease is widely accepted. Recently, we reported that anti-myelin basic protein (MBP) serum Abs from multiple sclerosis (MS) patients exhibit proteolytic activity toward the autoantigen. The aim of this study is to determine MBP epitopes specific for the autoantibodies in MS and compare these data with those from other neuronal disorders (OND), leading to the generation of new diagnostic and prognostic criteria. We constructed a MBP-derived recombinant "epitope library" covering the entire molecule. We used ELISA and PAGE/surface-enhanced laser desorption/ionization mass spectroscopy assays to define the epitope binding/cleaving activities of autoantibodies isolated from the sera of 26 MS patients, 22 OND patients, and 11 healthy individuals. The levels of autoantibodies to MBP fragments 48-70 and 85-170 as well as to whole MBP and myelin oligodendrocyte glycoprotein molecules were significantly higher in the sera of MS patients than in those of healthy donors. In contrast, selective reactivity to the two MBP fragments 43-68 and 146-170 distinguished the OND and MS patients. Patients with MS (77% of progressive and 85% of relapsing-remitting) but only 9% of patients with OND and no healthy donors were positive for catalysis, showing pronounced epitope specificity to the encephalitogenic MBP peptide 81-103. This peptide retained its substrate properties when flanked with two fluorescent proteins, providing a novel fluorescent resonance energy transfer approach for MS studies. Thus, anti-MBP autoantibody-mediated, epitope-specific binding and cleavage may be regarded as a specific characteristic of MS compared with OND and healthy donors and may serve as an additional biomarker of disease progression. C1 [Belogurov, Alexey A., Jr.; Kurkova, Inna N.; Zakharova, Maria Yu.; Souslova, Ekaterina A.; Gabibov, Alexander G.; Pononlarenko, Natalia A.] Russian Acad Sci, Inst Bioorgan Chem, Moscow, Russia. [Alehin, Alexander I.] Russian Acad Sci, Clin Hosp, Moscow, Russia. [Misikov, Viktor K.; Suchkov, Sergey V.; Kotov, Sergey V.] Vladimirsky Moscow REg Clin Inst, Moscow, Russia. [Friboulet, Alain; Thomas, Daniel; Avalle, Berangere] Univ Technol Compiegne, CNRS, Unite Mixte Rech, F-60206 Compiegne, France. [Morse, Herbert C., III] NIAID, Immunopathol Lab, Natl Inst Hlth, Rockville, MD 20852 USA. [Gabibov, Alexander G.] Russian Acad Sci, Inst Gene Biol, Moscow, Russia. RP Gabibov, AG (reprint author), Russian Acad Sci, Inst Bioorgan Chem, Miklucho Maklaia 16-10, Moscow, Russia. EM gabibov@ibch.ru RI Kotov, Sergey/E-4451-2017; OI Kotov, Sergey/0000-0002-8706-7317; Ponomarenko, Natalia/0000-0003-3129-3515; Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS NR 48 TC 57 Z9 63 U1 0 U2 8 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 15 PY 2008 VL 180 IS 2 BP 1258 EP 1267 PG 10 WC Immunology SC Immunology GA 250HG UT WOS:000252290000063 PM 18178866 ER PT J AU Guinane, CM Sturdevant, DE Herron-Olson, L Otto, M Smyth, DS Villaruz, AE Kapur, V Hartigan, PJ Smyth, CJ Fitzgerald, JR AF Guinane, Caitriona M. Sturdevant, Daniel E. Herron-Olson, Lisa Otto, Michael Smyth, Davida S. Villaruz, Amer E. Kapur, Vivek Hartigan, Patrick J. Smyth, Cyril J. Fitzgerald, J. Ross TI Pathogenomic analysis of the common bovine Staphylococcus aureus clone (ET3): Emergence of a virulent subtype with potential risk to public health SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PANTON-VALENTINE LEUKOCIDIN; TOXIC-SHOCK-SYNDROME; METHICILLIN-RESISTANT; MOLECULAR POPULATION; STREPTOLYSIN-S; PHI-PVL; GENES; STRAINS; AGR; MASTITIS AB A common clone (ET3) of Staphylococcus aureus is responsible for a large proportion of cases of bovine mastitis and occasionally causes zoonotic infections of humans. In the present study, we report the identification of a virulent clonal subtype (ST151) of ET3, which resulted in increased tissue damage and mortality in a mouse model of mastitis. ST151 has undergone extensive diversification in virulence and regulatory-gene content, including the acquisition of genetic elements encoding toxins not made by other ET3 strains. Furthermore, ST151 had elevated levels of RNAIII and cytolytic toxin-gene expression, consistent with the enhanced virulence observed during experimental infection. Previously, the ST151 clone was shown to be hypersusceptible to the acquisition of vancomycin-resistance genes from Enterococcus spp. Taken together, these data indicate the emergence of a virulent subtype of the common ET3 clone, which could present an enhanced risk to public health. C1 [Guinane, Caitriona M.; Fitzgerald, J. Ross] Univ Edinburgh, New Royal Infirm, Ctr Infect Dis, Edinburgh EH16 4SB, Midlothian, Scotland. [Hartigan, Patrick J.] Trinity Coll Dublin, Moyne Inst Prevent Med, Dept Physiol, Dublin, Ireland. [Smyth, Davida S.; Smyth, Cyril J.] Trinity Coll Dublin, Moyne Inst Prevent Med, Dept Microbiol, Dublin, Ireland. [Sturdevant, Daniel E.] NIAID, Res Technol Branch, NIH, Hamilton, MT USA. [Otto, Michael; Villaruz, Amer E.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Herron-Olson, Lisa; Kapur, Vivek] Univ Minnesota, Dept Vet Pathobiol, St Paul, MN 55108 USA. [Herron-Olson, Lisa; Kapur, Vivek] Univ Minnesota, Biomed Genom Ctr, St Paul, MN 55108 USA. RP Fitzgerald, JR (reprint author), Univ Edinburgh, New Royal Infirm, Ctr Infect Dis, Chancellors Bldg, Edinburgh EH16 4SB, Midlothian, Scotland. EM Ross.Fitzgerald@ed.ac.uk RI Kapur, Vivek/F-7610-2013; OI Kapur, Vivek/0000-0002-9648-0138; Otto, Michael/0000-0002-2222-4115 NR 40 TC 24 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2008 VL 197 IS 2 BP 205 EP 213 DI 10.1086/524689 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TX UT WOS:000252399200006 PM 18177250 ER PT J AU Lim, JK Louie, CY Glaser, C Jean, C Johnson, B Johnson, H McDermott, DH Murphy, PM AF Lim, Jean K. Louie, Christine Y. Glaser, Carol Jean, Cynthia Johnson, Bernard Johnson, Hope McDermott, David H. Murphy, Philip M. TI Genetic deficiency of chemokine receptor CCR5 is a strong risk factor for symptomatic West Nile Virus infection: A meta-analysis of 4 cohorts in the US epidemic SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Biodefense and Emerging Infectious Diseases CY MAY 16, 2007 CL NIH, Bethesda, MD HO NIH ID CCR5 PROMOTER POLYMORPHISM; UNITED-STATES; ENCEPHALITIS; MUTATION; BRAIN AB West Nile virus (WNV) causes disease in similar to 20% of infected humans. We previously reported that homozygosity for CCR5 Delta 32, a nonfunctional variant of chemokine receptor CCR5, is markedly increased among symptomatic WNV-seropositive patients from Arizona and Colorado. To confirm this, we analyzed cohorts from California and Illinois. An increase in CCR5-deficient subjects was found in both (for California, , lodds ratio [OR], 4.2 [95% confidence interval {CI}, 1.5-11.9] [P= .004]; for Illinois, OR, 3.1 [95% CI, 0.9-11.2] [P = .06]). A meta-analysis of all 4 cohorts showed an OR of 4.2 (95% CI, 2.1-8.3 [P < .0001]). Thus, CCR5 deficiency is a strong and consistent risk factor for symptomatic WNV infection in the United States. C1 [Lim, Jean K.; Louie, Christine Y.; McDermott, David H.; Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, Natl Inst Hlth, Bethesda, MD 20892 USA. [Glaser, Carol; Jean, Cynthia] Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Richmond, CA USA. [Johnson, Bernard; Johnson, Hope] Illinois Dept Publ Hlth, Div Labs, Chicago, IL USA. RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Lab Mol Immunol, Natl Inst Hlth, 9000 Rockville Pike,Bldg 10,Rm 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov OI McDermott, David/0000-0001-6978-0867 FU Intramural NIH HHS NR 15 TC 111 Z9 116 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2008 VL 197 IS 2 BP 262 EP 265 DI 10.1086/524691 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TX UT WOS:000252399200013 PM 18179388 ER PT J AU Andreasen, V Viboud, C Simonsen, L AF Andreasen, Viggo Viboud, Cecile Simonsen, Lone TI Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: Implications for pandemic control strategies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; MORTALITY; IMPACT; TRANSMISSION; POPULATION; DYNAMICS; VIRUS; AGE AB Background. The 1918-1919 A/H1N1 influenza pandemic killed similar to 50 million people worldwide. Historical records suggest that an early pandemic wave struck Europe during the summer of 1918. Methods. We obtained surveillance data that were compiled weekly, during 1910-1919, in Copenhagen, Denmark; the records included medically treated influenza-like illnesses (ILIs), hospitalizations, and deaths by age. We used a Serfling seasonal regression model to quantify excess morbidity and mortality, and we estimated the reproductive number (R) for the summer, fall, and winter pandemic waves. Results. A large epidemic occurred in Copenhagen during the summer of 1918; the age distribution of deaths was characteristic of the 1918-1919 A/H1N1 pandemic overall. That summer wave accounted for 29%-34% of all excess ILIs and hospitalizations during 1918, whereas the case-fatality rate (0.3%) was many-fold lower than that of the fall wave (2.3%). Similar patterns were observed in 3 other Scandinavian cities. R was substantially higher in summer (2.0-5.4) than in fall (1.2-1.6) in all cities. Conclusions. The Copenhagen summer wave may have been caused by a precursor A/H1N1 pandemic virus that transmitted efficiently but lacked extreme virulence. The R measured in the summer wave is likely a better approximation of transmissibility in a fully susceptible population and is substantially higher than that found in previous US studies. The summer wave may have provided partial protection against the lethal fall wave. C1 [Andreasen, Viggo] Roskilde Univ Ctr, Dept Sci, DK-4000 Roskilde, Denmark. [Viboud, Cecile] Fogarty Int Ctr, Bethesda, MD USA. [Simonsen, Lone] NIAID, NIH, Bethesda, MD 20892 USA. RP Andreasen, V (reprint author), Roskilde Univ Ctr, Dept Sci, DK-4000 Roskilde, Denmark. EM viggo@ruc.dk OI Simonsen, Lone/0000-0003-1535-8526 FU Intramural NIH HHS [Z99 TW999999] NR 40 TC 119 Z9 121 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2008 VL 197 IS 2 BP 270 EP 278 DI 10.1086/524065 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TX UT WOS:000252399200015 PM 18194088 ER PT J AU Strickler, HD Fazzari, M Kovacs, A Isasi, C Napolitano, LA Minkoff, H Gange, S Young, M Sharp, GB Kaplan, RC Cohen, M Gunter, MJ Harris, TG Yu, H Schoenbaum, E Landay, AL Anastos, K AF Strickler, Howard D. Fazzari, Melissa Kovacs, Andrea Isasi, Carmen Napolitano, Laura A. Minkoff, Howard Gange, Stephen Young, Mary Sharp, Gerald B. Kaplan, Robert C. Cohen, Mardge Gunter, Marc J. Harris, Tiffany G. Yu, Herbert Schoenbaum, Ellie Landay, Alan L. Anastos, Kathryn TI Associations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 with HIV disease progression in women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PROSTATE-CANCER CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; BREAST-CANCER; FACTOR-I; ANTIRETROVIRAL THERAPY; APOPTOSIS INDUCTION; HORMONE; INFECTION; IGFBP-3; PHOSPHORYLATION AB Background. The insulin-like growth factor (IGF) axis has been hypothesized to influence the rate of human immunodeficiency virus (HIV) disease progression. This premise is based largely on laboratory models showing that IGF-I stimulates thymic growth and increases lymphocyte numbers and that IGF-binding protein (IGFBP)-3 has an opposing effect, inhibiting hematopoietic stem cell development. Methods. We studied 1422 HIV-infected women enrolled in a large cohort that entailed semiannual follow-up (initiated in 1994). Baseline serum samples were tested for IGF-I and IGFBP-3 to determine their associations with incident clinical acquired immunodeficiency syndrome (AIDS) and CD4(+) T cell count decline prior to April 1996 (before the era of highly active antiretroviral therapy [HAART]). Results. Low IGF-I levels (P-trend = .02) and high IGFBP-3 levels (P-trend = .02) were associated with rapid CD4(+) T cell count decline. Only IGFBP-3, however, was significantly associated with AIDS incidence (hazard ratio for highest vs. lowest quartile, 2.65 [95% confidence interval, 1.30-5.42]; P-trend = .02) in multivariable models. Conclusions. These findings suggest that serum levels of IGFBP-3 (and possibly IGF-I) are associated with the rate of HIV disease progression in women and, more broadly, that interindividual heterogeneity in the IGF axis may influence HIV pathogenesis. If correct, the IGF axis could be a target for interventions to slow HIV disease progression and extend the time before use of HAART becomes necessary. C1 [Strickler, Howard D.; Fazzari, Melissa; Isasi, Carmen; Kaplan, Robert C.; Gunter, Marc J.; Harris, Tiffany G.; Schoenbaum, Ellie; Anastos, Kathryn] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA. [Kovacs, Andrea] Univ So Calif, Los Angeles, CA USA. [Napolitano, Laura A.] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. [Gange, Stephen] Johns Hopkins Univ, Baltimore, MD USA. [Sharp, Gerald B.] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. [Young, Mary] Georgetown Univ, Washington, DC USA. [Cohen, Mardge; Landay, Alan L.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Cohen, Mardge; Landay, Alan L.] John H Stroger Hosp Cook Cty, Chicago, IL USA. [Yu, Herbert] Yale Univ, New Haven, CT USA. RP Strickler, HD (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer 1308-B, Bronx, NY 10461 USA. EM strickle@aecom.yu.edu RI Kaplan, Robert/A-2526-2011; OI Gange, Stephen/0000-0001-7842-512X FU NCRR NIH HHS [M01 RR000079, M01-RR-00071, M01-RR-00083, M01-RR-00079, M01 RR000083, M01 RR000071]; NIAID NIH HHS [U01-AI-34993, P30 AI051519, R01 AI052065-01, U01 AI034994, U01 AI042590, AI-51519, U01-AI-31834, U01 AI034993, U01 AI031834, U01-AI-35004, U01-AI-34989, U01 AI035004, U01 AI034989, U01-AI-34994, R01 AI052065, U01-AI-42590]; NICHD NIH HHS [U01-HD-32632, U01 HD032632] NR 43 TC 9 Z9 9 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2008 VL 197 IS 2 BP 319 EP 327 DI 10.1086/524848 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 251TX UT WOS:000252399200022 PM 18177247 ER PT J AU Nijboer, F Furdea, A Gunst, I Mellinger, J McFarland, DJ Birbaumer, N Kubler, A AF Nijboer, Femke Furdea, Adrian Gunst, Ingo Mellinger, Juergen McFarland, Dennis J. Birbaumer, Niels Kuebler, Andrea TI An auditory brain-computer interface (BCI) SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE brain-computer interface; locked-in state; EEG; sensorimotor rhythm; auditory feedback; motivation ID COMMUNICATION; FEEDBACK; ALS AB Brain-computer interfaces (BCIs) translate brain activity into signals controlling external devices. BCIs based on visual stimuli can maintain communication in severely paralyzed patients, but only if intact vision is available. Debilitating neurological disorders however, may lead to loss of intact vision. The current study explores the feasibility of an auditory BCI. Sixteen healthy volunteers participated in three training sessions consisting of 30 2-3 min runs in which they learned to increase or decrease the amplitude of sensorimotor rhythms (SMR) of the EEG. Half of the participants were presented with visual and half with auditory feedback. Mood and motivation were assessed prior to each session. Although BCI performance in the visual feedback group was superior to the auditory feedback group there was no difference in performance at the end of the third session. Participants in the auditory feedback group learned slower, but four out of eight reached an accuracy of over 70% correct in the last session comparable to the visual feedback group. Decreasing performance of some participants in the visual feedback group is related to mood and motivation. We conclude that with sufficient training time an auditory BCI may be as efficient as a visual BCI Mood and motivation play a role in learning to use a BCI. (C) 2007 Elsevier B.V. All rights reserved. C1 [Nijboer, Femke; Furdea, Adrian; Gunst, Ingo; Mellinger, Juergen; Birbaumer, Niels; Kuebler, Andrea] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. [McFarland, Dennis J.] New York State Dept Hlth, Wadsworth Ctr Labs & Res, Lab Nervous Syst Disorders, Albany, NY 12201 USA. [Birbaumer, Niels] NINDS, NIH, Human Cortical Physiol Unit, Bethesda, MD 20892 USA. RP Nijboer, F (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM fernke.nijboer@uni-tuebingen.de; adrian.furdea@uni-tuebingen.de; ingo.gunst@gmx.de; juergen.mellinger@uni-tuebingen.de; mcfarlan@wadsworth.org; niels.birbaumer@uni-tuebingen.de; andrea.kuebler@uni-tuebingen.de OI Kubler, Andrea/0000-0003-4876-0415 FU NICHD NIH HHS [R01 HD030146] NR 17 TC 141 Z9 145 U1 2 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 15 PY 2008 VL 167 IS 1 BP 43 EP 50 DI 10.1016/j.jneumeth.2007.02.009 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 248OU UT WOS:000252164300006 PM 17399797 ER PT J AU Reis, J Swayne, OB Vandermeeren, Y Camus, M Dimyan, MA Harris-Love, M Perez, MA Ragert, P Rothwell, JC Cohen, LG AF Reis, Janine Swayne, Orlando B. Vandermeeren, Yves Camus, Mickael Dimyan, Michael A. Harris-Love, Michelle Perez, Monica A. Ragert, Patrick Rothwell, John C. Cohen, Leonardo G. TI Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID LATENCY AFFERENT INHIBITION; INTERVAL INTRACORTICAL INHIBITION; PAIRED ASSOCIATIVE STIMULATION; SELECTIVE FINGER MOVEMENT; USE-DEPENDENT PLASTICITY; DORSAL PREMOTOR CORTEX; CROSS-MODAL PLASTICITY; HAND MUSCLE ACTIVATION; HUMAN CEREBRAL-CORTEX; ISCHEMIC NERVE BLOCK AB Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electro-physiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail. C1 [Swayne, Orlando B.; Rothwell, John C.] Inst Neurol, Sobell Dept Motor Neurosci, London WC1N 3BG, England. [Reis, Janine; Swayne, Orlando B.; Vandermeeren, Yves; Camus, Mickael; Dimyan, Michael A.; Harris-Love, Michelle; Perez, Monica A.; Ragert, Patrick; Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Reis, J (reprint author), NINDS, Human Cort Physiol Sect, NIH, 10 Ctr Dr,Bldg 10,Rm 10,5 N226, Bethesda, MD 20892 USA. RI Dimyan, Michael/B-1715-2012; Harris-Love, Michelle/J-1388-2014; OI Harris-Love, Michelle/0000-0001-5571-3858; Dimyan, Michael/0000-0002-9715-9741; Rothwell, John/0000-0003-1367-6467 FU Intramural NIH HHS; Medical Research Council [G0500258] NR 182 TC 261 Z9 265 U1 6 U2 42 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 15 PY 2008 VL 586 IS 2 BP 325 EP 351 DI 10.1113/jphysiol.2007.144824 PG 27 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 255SX UT WOS:000252678800004 PM 17974592 ER PT J AU Thacker, EL Chen, H Patel, AV McCullough, ML Calle, EE Thun, MJ Schwarzschild, MA Ascherio, A AF Thacker, Evan L. Chen, Honglei Patel, Alpa V. McCullough, Marjorie L. Calle, Eugenia E. Thun, Michael J. Schwarzschild, Michael A. Ascherio, Alberto TI Recreational physical activity and risk of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; epidemiology; cohort study; behavioral risk factors; physical activity ID II NUTRITION COHORT; URIC-ACID LEVELS; CANCER PREVENTION; EXERCISE; DIAGNOSIS; ACCURACY AB The purpose of this study was to investigate associations between recreational physical activity and Parkinson's disease (PD) risk. We prospectively followed 143,325 participants in the Cancer Prevention Study 11 Nutrition Cohort from 1992 to 2001 (mean age at baseline = 63). Recreational physical activity was estimated at baseline from the reported number of hours per week on average spent performing light intensity activities (walking, dancing) and moderate to vigorous intensity activities (jogging/running, lap swimming, tennis/racquetball, bicycling/stationary bike, aerobics/calisthenics). Incident cases of PD (n = 413) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Risk of PD declined in the highest categories of baseline recreational activity. The RR comparing the highest category of total recreational activity (men >= 23 metabolic equivalent task-hours/week [MET-h/wk], women >= 18.5 MET-h/wk) to no activity was 0.8 (95% CI: 0.6, 1.2; P trend = 0.07). When light activity and moderate to vigorous activity were examined separately, only the latter was found to be associated with PD risk. The RR comparing the highest category of moderate to vigorous activity (men >= 16 MET-h/wk, women >= 11.5 MET-h/wk) to the lowest (0 MET-h/wk) was 0.6 (95% CI: 0.4, 1.0; P trend = 0.02). These results did not differ significantly by gender. The results were similar when we excluded cases with symptom onset in the first 4 years of follow-up. Our results may be explained either by a reduction in PD risk through moderate to vigorous activity, or by decreased baseline recreational activity due to preclinical PD. (D 2007 Movement Disorder Society. C1 [Thacker, Evan L.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Patel, Alpa V.; McCullough, Marjorie L.; Calle, Eugenia E.; Thun, Michael J.] Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Thacker, EL (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. EM ethacker@post.harvard.edu OI Thacker, Evan/0000-0002-3813-0885; Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [NS048517, R01 NS048517, R01 NS048517-01A2] NR 22 TC 64 Z9 67 U1 1 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN 15 PY 2008 VL 23 IS 1 BP 69 EP 74 DI 10.1002/mds.21772 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 258WS UT WOS:000252901400010 PM 17960818 ER PT J AU Kimes, AS Chefer, SI Matochik, JA Contoreggi, CS Vaupel, DB Stein, EA Mukhin, AG AF Kimes, Alane S. Chefer, Svetlana I. Matochik, John A. Contoreggi, Carlo S. Vaupel, D. Bruce Stein, Elliot A. Mukhin, Alexey G. TI Quantification of nicotinic acetylcholine receptors in the human brain with PET: Bolus plus infusion administration of 2-[F-18]F-A85380 SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; GRAPHICAL ANALYSIS; PARKINSON-DISEASE; BINDING; NONSMOKERS; SMOKERS; NEURORECEPTOR; EQUILIBRIUM; ALPHA4BETA2; DENSITY AB Quantitative analysis of most positron emission tomography (PET) data requires arterial blood sampling and dynamic scanning when the radioligand is administered as a bolus injection. Less invasive studies can be accomplished if the radioligand is administered as a bolus plus constant infusion (B/I). The purpose of the current study was to evaluate a B/I paradigm for quantifying high affinity nicotinic acetylcholine receptors (nAChRs) with PET and 2-[F-18]F-A85380 (2FA). Seven volunteers underwent a study in which 2FA was administered as a bolus injection and another study in which the 2FA was administered by B/I (Kbolus = 500 min). We evaluated the feasibility of using scans of a 2 h duration starting 6 h after the start of the 2FA administration and data from venous blood. Radioactivity in the brain and in arterial and venous plasma reached steady state by 6 h. Volumes of distribution (V-T) calculated from the ratio of radioactivity in the brain areas of interest to the radioactivity corresponding to unbound, unmetabolized 2FA in venous plasma at steady state in the B/I studies were very similar to those calculated from time activity curves of unbound, unmetabolized 2FA in arterial plasma and regional brain radioactivity from 8-h dynamic scans after bolus administration of 2FA. The results of repeated PET studies with 2FA showed a high reproducibility of V-T, measurements. We conclude that B/I methodology will be useful for clinical and research studies of brain nAChRs. Published by Elsevier Inc. C1 [Kimes, Alane S.; Chefer, Svetlana I.; Matochik, John A.; Contoreggi, Carlo S.; Vaupel, D. Bruce; Stein, Elliot A.; Mukhin, Alexey G.] NIDA, IRP, NIH, DHHS,Neuroimaging Res Branch, Baltimore, MD 21224 USA. RP Mukhin, AG (reprint author), NIDA, IRP, NIH, DHHS,Neuroimaging Res Branch, Baltimore, MD 21224 USA. EM a.mukhin@duke.edu RI Stein, Elliot/C-7349-2008 FU Intramural NIH HHS [Z01 DA000405-11] NR 30 TC 26 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2008 VL 39 IS 2 BP 717 EP 727 DI 10.1016/j.neuroimage.2007.09.015 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 241CL UT WOS:000251634400017 PM 17962044 ER PT J AU Ono, F AF Ono, Fumihito TI An Emerging Picture of Synapse Formation: A Balance of Two Opposing Pathways SO SCIENCE SIGNALING LA English DT Article AB The neuromuscular junction (NMJ) is a well-studied chemical synapse and has served as a tractable model system to clarify how synapse formation occurs. Proteins on both the presynaptic and postsynaptic sides collaborate to induce the high-density accumulation of acetylcholine receptors (AChRs) at the NMJ. Two opposing pathways work in this process: A dispersing pathway works through acetylcholine and the AChR, and a clustering pathway works through agrin and the transmembrane tyrosine kinase MuSK. The molecular mechanisms underlying these two signaling cascades are beginning to be understood. C1 NIAAA, Lab Mol Physiol, Bethesda, MD 20892 USA. RP Ono, F (reprint author), NIAAA, Lab Mol Physiol, Bethesda, MD 20892 USA. EM onof@mail.nih.gov RI ono, fumihito/A-6570-2008 NR 32 TC 6 Z9 6 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JAN 15 PY 2008 VL 1 IS 2 AR pe3 DI 10.1126/stke.12pe3 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V10UU UT WOS:000207489700002 PM 18270167 ER PT J AU Divi, RL Doerge, DR Twaddle, NC Shockley, ME Claire, MCS Harbaugh, JW Harbaugh, SW Poirier, MC AF Divi, Rao L. Doerge, Daniel R. Twaddle, Nathan C. Shockley, Marie E. Claire, Marisa C. St. Harbaugh, Jefftey W. Harbaugh, Steven W. Poirier, Miriam C. TI Metabolism and pharmacokinetics of the combination Zidovudine plus Lamivudine in the adult Erythrocebus patas monkey determined by liquid chromatography-tandem mass spectrometric analysis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Combivir; AZT; AZT-glucuronide; AMT; 3TC; tandem mass spectrometry; serum ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; ANTIRETROVIRAL NUCLEOSIDE; MITOCHONDRIAL COMPROMISE; DRUG-INTERACTIONS; INFECTED PATIENTS; PREGNANT BABOON; RHESUS-MONKEYS; THERAPY; INFANTS AB Because of their similarity to humans, non-human primates constitute useful preclinical models in which to examine potential human drug toxicities. Antiretroviral nucleoside reverse transcriptase inhibitor (NRTI) toxicity is currently under investigation in Erythrocebus patas monkeys, and whereas NRTI pharmacokinetics have been studied in other monkey species, pharmacokinetics for Zidovudine plus Lamivudine (AZT/3TC) dosing have not been reported in the patas. Here we present 24 h serum pharmacokinetic parameters after a single oral exposure to the combination of AZT (40 mg) and 3TC (24 mg), doses equivalent to a human daily dose of Combivir (R). The patas (n = 3) AZT/3TC pharmacokinetic profiles were similar to those seen in other primate species. Average maximum serum concentrations (C-max) for AZT and 3TC were 2.35 and 2.65 mu g/ml, respectively, and were observed at 0.83 h (T-max). C-max was 13.34 mu g/ml for the AZT-glucuronide (AZT-G) and was 0.023 mu g/ml for the potentially toxic minor metabolite 3'-amino-3'-deoxythymidine (AMT), both occurring at about 1 h after dosing. Similar elimination half-times, 0.70 and 0.68 h(-1), were found for AZT and AZT-G, respectively, while 3TC was eliminated about half as fast (0.33 h(-1)) resulting in AUC((0-infinity)) values of 6.97 mu g/ml h for 3TC, 2.99 mu g/ml h for AZT, 20.5 mu g/ml h for AZT-G and 0.002 for AMT 6.97 mu g/ml h. This study shows similar metabolism and pharmacokinetics for oral administration of AZT/3TC in the adult patas monkey, other primate species and humans. The data validate the use of the patas monkey for studies of NRTI toxicity. Published by Elsevier Inc. C1 [Divi, Rao L.; Shockley, Marie E.; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBR,CCR, NIH, Bethesda, MD 20892 USA. [Doerge, Daniel R.; Twaddle, Nathan C.] Natl Ctr Toxicol Res, Div Biochem Toxicol, FDA, Jefferson, AR 72079 USA. [Claire, Marisa C. St.; Harbaugh, Jefftey W.; Harbaugh, Steven W.] BioQual Inc, Rockville, MD 20850 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, LCBR,CCR, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov FU Intramural NIH HHS NR 35 TC 5 Z9 5 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 15 PY 2008 VL 226 IS 2 BP 206 EP 211 DI 10.1016/j.taap.2007.09.007 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 255IY UT WOS:000252652900011 PM 17949768 ER PT J AU Seidenfeld, J Horstmann, E Emanuel, EJ Grady, C AF Seidenfeld, Justine Horstmann, Elizabeth Emanuel, Ezekiel J. Grady, Christine TI Participants in phase 1 oncology research trials - Are they vulnerable? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID I CLINICAL-TRIALS; QUALITY-OF-LIFE; PATIENT EXPECTATIONS; DECISION-MAKING; ETHICS; PROGNOSIS; BENEFITS; AGENTS; RISKS AB Phase I oncology trials involve risk and offer a relatively low prospect of benefit to participants. Some claim that participants constitute a vulnerable population requiring special protections. We undertook this study to determine whether phase I oncology trial participants have demographic and health status characteristics of a vulnerable population. We reviewed participant demographic and health status data from phase I trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute that began between 1991 and 2002 and from 11 previously published studies. Main outcome measures were median age, sex, race/ethnicity, performance status, previous therapy, educational achievement level, and health insurance coverage. Almost 10 000 participants in trials sponsored by the Cancer Therapy Evaluation Program had a median age of 57 years, 90% self-identified as white, 93% had near-normal performance status, 85% had some form of health insurance, and 92% had been previously treated for cancer; 20 000 individuals from published studies had comparable profiles. The demographic and health status characteristics of phase I oncology trial participants are not those of a rap conventional vulnerable population and suggest little reason to assume that, as a group, they have a compromised ability to understand information or to make informed and voluntary decisions. C1 [Seidenfeld, Justine; Horstmann, Elizabeth; Emanuel, Ezekiel J.; Grady, Christine] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM cgrady@nih.gov NR 37 TC 29 Z9 29 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 14 PY 2008 VL 168 IS 1 BP 16 EP 20 DI 10.1001/archinternmed.2007.6 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 249RX UT WOS:000252248500003 PM 18195190 ER PT J AU Jochim, RC Teixeira, CR Laughinghouse, A Mu, JB Oliveira, F Gomes, RB Elnaiem, DE Valenzuela, JG AF Jochim, Ryan C. Teixeira, Clarissa R. Laughinghouse, Andre Mu, Jianbing Oliveira, Fabiano Gomes, Regis B. Elnaiem, Dia-Eldin Valenzuela, Jesus G. TI The midgut transcriptome of Lutzomyia longipalpis: comparative analysis of cDNA libraries from sugar-fed, blood-fed, post-digested and Leishmania infantum chagasi-infected sand flies SO BMC GENOMICS LA English DT Article ID PHLEBOTOMUS-PAPATASI; RECOGNITION PROTEIN; CLONING; GENE; PEPTIDOGLYCAN; EXPRESSION; INHIBITOR; SANDFLIES; SIALOME; VECTOR AB Background: In the life cycle of Leishmania within the alimentary canal of sand flies the parasites have to survive the hostile environment of blood meal digestion, escape the blood bolus and attach to the midgut epithelium before differentiating into the infective metacyclic stages. The molecular interactions between the Leishmania parasites and the gut of the sand fly are poorly understood. In the present work we sequenced five cDNA libraries constructed from midgut tissue from the sand fly Lutzomyia longipalpis and analyzed the transcripts present following sugar feeding, blood feeding and after the blood meal has been processed and excreted, both in the presence and absence of Leishmania infantum chagasi. Results: Comparative analysis of the transcripts from sugar-fed and blood-fed cDNA libraries resulted in the identification of transcripts differentially expressed during blood feeding. This included upregulated transcripts such as four distinct microvillar-like proteins (LuloMVP1, 2, 4 and 5), two peritrophin like proteins, a trypsin like protein (Lltryp1), two chymotrypsin like proteins (LuloChym1A and 2) and an unknown protein. Downregulated transcripts by blood feeding were a microvillar-like protein (LuloMVP3), a trypsin like protein (Lltryp2) and an astacin-like metalloprotease (LuloAstacin). Furthermore, a comparative analysis between blood-fed and Leishmania infected midgut cDNA libraries resulted in the identification of the transcripts that were differentially expressed due to the presence of Leishmania in the gut of the sand fly. This included down regulated transcripts such as four microvillar-like proteins (LuloMVP1,2, 4 and 5), a Chymotrypsin (LuloChym1A) and a carboxypeptidase (LuloCpepA1), among others. Upregulated midgut transcripts in the presence of Leishmania were a peritrophin like protein (LuloPer1), a trypsin-like protein (Lltryp2) and an unknown protein. Conclusion: This transcriptome analysis represents the largest set of sequence data reported from a specific sand fly tissue and provides further information of the transcripts present in the sand fly Lutzomyia longipalpis. This analysis provides the detailed information of molecules present in the midgut of this sand fly and the transcripts potentially modulated by blood feeding and by the presence of the Leishmania parasite. More importantly, this analysis suggests that Leishmania infantum chagasi alters the expression profile of certain midgut transcripts in the sand fly during blood meal digestion and that this modulation may be relevant for the survival and establishment of the parasite in the gut of the fly. Moreover, this analysis suggests that these changes may be occurring during the digestion of the blood meal and not afterwards. C1 [Jochim, Ryan C.; Teixeira, Clarissa R.; Oliveira, Fabiano; Gomes, Regis B.; Elnaiem, Dia-Eldin; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Jochim, Ryan C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Laughinghouse, Andre] NIAID, Entomol Sect, LMVR, NIH, Rockville, MD 20852 USA. [Mu, Jianbing] NIAID, Malaria Genom Sect, LMVR, NIH, Rockville, MD 20852 USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM rjochim@niaid.nih.gov; teixeirac@niaid.nih.gov; alaughing@niaid.nih.gov; jmu@niaid.nih.gov; loliveira@niaid.nih.gov; gomesr@niaid.nih.gov; elnaiemd@niaid.nih.gov; jvalenzuela@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009; Jochim, Ryan/C-6756-2013 OI Oliveira, Fabiano/0000-0002-7924-8038; FU Intramural NIH HHS NR 24 TC 50 Z9 50 U1 0 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JAN 14 PY 2008 VL 9 AR 15 DI 10.1186/1471-2164-9-15 PG 24 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 267WQ UT WOS:000253540300002 PM 18194529 ER PT J AU Tomita, T Kimura, S AF Tomita, Takeshi Kimura, Shioko TI Regulation of mouse Scgb3a1 gene expression by NF-Y and association of CpG methylation with its tissue-specific expression SO BMC MOLECULAR BIOLOGY LA English DT Article ID ETS TRANSCRIPTION FACTORS; RNA-POLYMERASE-II; DNA METHYLATION; B-SUBUNIT; CBF/NF-Y; PROTEIN; HIN-1; FAMILY; UGRP2; INDUCTION AB Background: Secretoglobin (SCGB) 3A1 is a secretory protein of small molecular weight with tumor suppressor function. It is highly expressed in lung and trachea in both human and mouse, with additional tissues expressing the protein that differ depending on the species. However, little is known about the function and transcriptional regulation of this gene in normal mouse tissues. Results: By reporter gene transfection and gel mobility shift analyses, we demonstrated that expression of the mouse Scgb3a1 gene is regulated by a PU-box binding protein and a ubiquitous transcription factor NF-Y that respectively binds to the PU-boxes located at -99 to -105 bp and 158 to -164 bp, and the "CCAAT" binding sites located at -425 to -429 bp and -498 to -502 bp from the transcription start site of the gene. However, the effect of PU-box binding protein on transcriptional activation is minimal as compared to NF-Y, suggesting that NF-Y is a more critical transcription factor for mouse Scgb3a1 gene transcription. Despite that NF-Y is a ubiquitous factor, Scgb3a1 is highly expressed only in mouse lung and mtCC cells that are derived from SV40 transformed mouse Clara cells, but not in ten other mouse tissues/cells examined. Gene methylation analysis revealed that within 600 bp of the Scgb3a1 gene promoter region, there are nine CpG methylation sites present, of which two CpGs closest to the transcription start site of the gene are unmethylated in the tissues/cells expressing Scgb3a1. Conclusion: A ubiquitous transcription factor NF-Y binds to and activates expression of the mouse Scgb3a1 gene and tissue-specific expression of the gene is associated with CpG methylation of the promoter. C1 [Tomita, Takeshi; Kimura, Shioko] NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Tomita, T (reprint author), NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. EM tomitat@mail.nih.gov; kimuras@mail.nih.gov FU Intramural NIH HHS [Z01 BC010449-06, Z99 CA999999] NR 40 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2199 J9 BMC MOL BIOL JI BMC Mol. Biol. PD JAN 14 PY 2008 VL 9 AR 5 DI 10.1186/1471-2199-9-5 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 273YE UT WOS:000253967400003 PM 18194566 ER PT J AU Meaburn, KJ Misteli, T AF Meaburn, Karen J. Misteli, Tom TI Locus-specific and activity-independent gene repositioning during early tumorigenesis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ORDER CHROMATIN ARRANGEMENTS; SPATIAL GENOME ORGANIZATION; MAMMARY EPITHELIAL-CELLS; EWING SARCOMA-CELLS; CHROMOSOME TERRITORIES; BREAST-CANCER; NUCLEAR-ORGANIZATION; INTERPHASE NUCLEI; INACTIVE GENES; X-CHROMOSOME AB The mammalian genome is highly organized within the cell nucleus. The nuclear position of many genes and genomic regions changes during physiological processes such as proliferation, differentiation, and disease. It is unclear whether disease-associated positioning changes occur specifically or are part of more global genome reorganization events. Here, we have analyzed the spatial position of a defined set of cancer-associated genes in an established mammary epithelial three-dimensional cell culture model of the early stages of breast cancer. We find that the genome is globally reorganized during normal and tumorigenic epithelial differentiation. Systematic mapping of changes in spatial positioning of cancer-associated genes reveals gene-specific positioning behavior and we identify several genes that are specifically repositioned during tumorigenesis. Alterations of spatial positioning patterns during differentiation and tumorigenesis were unrelated to gene activity. Our results demonstrate the existence of activity-independent genome repositioning events in the early stages of tumor formation. C1 [Meaburn, Karen J.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov OI Meaburn, Karen/0000-0002-1327-5957 FU Intramural NIH HHS NR 67 TC 80 Z9 84 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 14 PY 2008 VL 180 IS 1 BP 39 EP 50 DI 10.1083/jcb.200708204 PG 12 WC Cell Biology SC Cell Biology GA 256RH UT WOS:000252746800007 PM 18195100 ER PT J AU Lim, Y Lim, ST Tomar, A Gardel, M Bernard-Trifilo, JA Chen, XL Uryu, SA Canete-Soler, R Zhai, J Lin, H Schlaepfer, WW Nalbant, P Bokoch, G Ilic, D Waterman-Storer, C Schlaepfer, DD AF Lim, Yang Lim, Ssang-Taek Tomar, Alok Gardel, Margaret Bernard-Trifilo, Joie A. Chen, Xiao Lei Uryu, Sean A. Canete-Soler, Rafaela Zhai, Jinbin Lin, Hong Schlaepfer, William W. Nalbant, Perihan Bokoch, Gary Ilic, Dusko Waterman-Storer, Clare Schlaepfer, David D. TI PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; MIGRATING CELLS; BINDING PROTEIN; SIGNALING EVENTS; MATRIX ADHESIONS; LEADING-EDGE; NULL CELLS; KINASE FAK; C-SRC; ACTIVATION AB Integrin binding to matrix proteins such as fibronectin (FN) leads to formation of focal adhesion (FA) cellular contact sites that regulate migration. RhoA GTPases facilitate FA formation, yet FA-associated RhoA-specific guanine nucleotide exchange factors (GEFs) remain unknown. Here, we show that proline-rich kinase-2 (Pyk2) levels increase upon loss of focal adhesion kinase (FAK) in mouse embryonic fibroblasts (MEFs). Additionally, we demonstrate that Pyk2 facilitates deregulated RhoA activation, elevated FA formation, and enhanced cell proliferation by promoting p190RhoGEF expression. In normal MEFs, p190RhoGEF knockdown inhibits FN-associated RhoA activation, FA formation, and cell migration. Knockdown of p190RhoGEF-related GEFH1 does not affect FA formation in FAK(-/-) or normal MEFs. p190RhoGEF overexpression enhances RhoA activation and FA formation in MEFs dependent on FAK binding and associated with p190RhoGEF FA recruitment and tyrosine phosphorylation. These studies elucidate a compensatory function for Pyk2 upon FAK loss and identify the FAK-p190RhoGEF complex as an important integrin-proximal regulator of FA formation during FN-stimulated cell motility. C1 [Lim, Yang; Lim, Ssang-Taek; Tomar, Alok; Chen, Xiao Lei; Uryu, Sean A.; Schlaepfer, David D.] Univ Calif San Diego, Moores Canc Ctr, Dept Reprod Med, La Jolla, CA 92093 USA. [Gardel, Margaret] Univ Chicago, Dept Phys, Chicago, IL 60637 USA. [Bernard-Trifilo, Joie A.] Millipores Biosci, Temecula, CA 92590 USA. [Canete-Soler, Rafaela; Zhai, Jinbin; Lin, Hong; Schlaepfer, William W.] Univ Penn, Div Neuropathol, Philadelphia, PA 19104 USA. [Nalbant, Perihan; Bokoch, Gary] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. [Ilic, Dusko] Stemlifeline Inc, San Carlos, CA 94070 USA. [Waterman-Storer, Clare] NIH, Heart Lung & Blood Inst, Bethesda, MD 20892 USA. RP Schlaepfer, DD (reprint author), Univ Calif San Diego, Moores Canc Ctr, Dept Reprod Med, La Jolla, CA 92093 USA. EM dschlaepfer@ucsd.edu RI Gardel, Margaret/D-1703-2012; OI Waterman, Clare/0000-0001-6142-6775 FU NCI NIH HHS [R01 CA087038, R01 CA075240, CA75240, CA102310, R01 CA102310, R29 CA075240, CA87038]; NIGMS NIH HHS [R01 GM067230, GM67230, U01 GM067230]; NINDS NIH HHS [NS515722] NR 50 TC 120 Z9 123 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 14 PY 2008 VL 180 IS 1 BP 187 EP 203 DI 10.1083/jcb.200708194 PG 17 WC Cell Biology SC Cell Biology GA 256RH UT WOS:000252746800018 PM 18195107 ER PT J AU Beck-Engeser, GB Lum, AM Huppi, K Caplen, NJ Wang, BB Wabl, M AF Beck-Engeser, Gabriele B. Lum, Amy M. Huppi, Konrad Caplen, Natasha J. Wang, Bruce B. Wabl, Matthias TI Pvt1-encoded microRNAs in oncogenesis SO RETROVIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; MYC TRANSGENIC MICE; INSERTIONAL MUTAGENESIS; RAT THYMOMAS; MOUSE; TRANSLOCATIONS; ACTIVATION; LYMPHOMA; CANCER; GENES AB Background: The functional significance of the Pvt1 locus in the oncogenesis of Burkitt's lymphoma and plasmacytomas has remained a puzzle. In these tumors, Pvt1 is the site of reciprocal translocations to immunoglobulin loci. Although the locus encodes a number of alternative transcripts, no protein or regulatory RNA products were found. The recent identification of noncoding microRNAs encoded within the PVT1 region has suggested a regulatory role for this locus. Results: The mouse Pvt1 locus encodes several microRNAs. In mouse T cell lymphomas induced by retroviral insertions into the locus, the Pvt1 transcripts, and at least one of their microRNA products, mmu-miR-1204 are overexpressed. Whereas up to seven co-mutations can be found in a single tumor, in over 2,000 tumors none had insertions into both the Myc and Pvt1 loci. Conclusion: Judging from the large number of integrations into the Pvt1 locus-more than in the nearby Myc locus-Pvt1 and the microRNAs encoded by it are as important as Myc in T lymphomagenesis, and, presumably, in T cell activation. An analysis of the co-mutations in the lymphomas likely place Pvt1 and Myc into the same pathway. C1 [Beck-Engeser, Gabriele B.; Wabl, Matthias] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Lum, Amy M.; Wang, Bruce B.] Picobella LLC, Burlingame, CA 94010 USA. [Huppi, Konrad; Caplen, Natasha J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wabl, M (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. EM Gabriele.Beck-Engeser@ucsf.edu; amy@picobella.com; huppi@helix.nih.gov; ncaplen@mail.nih.gov; bruce@picobella.com; mutator@ucsf.edu RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 FU Intramural NIH HHS; NCI NIH HHS [R01 CA100266, R01CA100266] NR 37 TC 54 Z9 57 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 14 PY 2008 VL 5 AR 4 DI 10.1186/1742-4690-5-4 PG 14 WC Virology SC Virology GA 271NI UT WOS:000253794700001 PM 18194563 ER PT J AU Girroir, EE Hollingshead, HE Billin, AN Willson, TM Robertson, GP Sharma, AK Amin, S Gonzalez, FJ Peters, JM AF Girroir, Elizabeth E. Hollingshead, Holly E. Billin, Andrew N. Willson, Timothy M. Robertson, Gavin P. Sharma, Arun K. Amin, Shantu Gonzalez, Frank J. Peters, Jeffrey M. TI Peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines SO TOXICOLOGY LA English DT Article DE peroxisome proliferator-activated receptor; melanoma; breast cancer; nuclear receptor; cell proliferation ID E-2 SIGNALING PATHWAYS; DELTA AGONIST; CARCINOMA-CELLS; BETA; DIFFERENTIATION; EXPRESSION; CHOLESTEROL; ALPHA; MICE; COLON AB The development of peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) ligands for the treatment of diseases including metabolic syndrome, diabetes and obesity has been hampered due to contradictory findings on their potential safety. For example, while some reports show that ligand activation of PPAR beta/delta promotes the induction of terminal differentiation and inhibition of cell growth, other reports suggest that PPAR beta/delta ligands potentiate tumorigenesis by increasing cell proliferation. Some of the contradictory findings could be due in part to differences in the ligand examined, the presence or absence of serum in cell cultures, differences in cell lines or differences in the method used to quantify cell growth. For these reasons, this study examined the effect of ligand activation of PPAR beta/delta on cell growth of two human cancer cell lines, MCF7 (breast cancer) and UACC903 (melanoma) in the presence or absence of serum using two highly specific PPAR beta/delta ligands, GW0742 or GW501516. Culturing cells in the presence of either GW0742 or GW501516 caused upregulation of the known PPAR beta/delta target gene angiopoiefin-like protein 4 (ANGPTL4). Inhibition of cell growth was observed in both cell lines cultured in the presence of either GW0742 or GW501516, and the presence or absence of serum had little influence on this inhibition. Results from the present studies demonstrate that ligand activation of PPAR beta/delta inhibits the growth of both MCF7 and UACC903 cell lines and provide further evidence that PPAR beta/delta ligands are not mitogenic in human cancer cell lines. Published by Elsevier Ireland Ltd. C1 [Girroir, Elizabeth E.; Hollingshead, Holly E.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Girroir, Elizabeth E.; Hollingshead, Holly E.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Hollingshead, Holly E.; Peters, Jeffrey M.] Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA. [Billin, Andrew N.; Willson, Timothy M.] GlaxoSmithKline Inc, Nucl Receptor Discovery Res, Res Triangle Pk, NC 27709 USA. [Robertson, Gavin P.; Sharma, Arun K.; Amin, Shantu] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Penn State Canc Inst, Hershey, PA 17033 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp2l@psu.edu RI Peters, Jeffrey/D-8847-2011; OI Billin, Andrew/0000-0001-7752-0934 FU NCI NIH HHS [R01 CA097999-05, CA124533, CA97999, R01 CA097999, R01 CA124533, R01 CA124533-01] NR 48 TC 40 Z9 43 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 14 PY 2008 VL 243 IS 1-2 BP 236 EP 243 DI 10.1016/j.tox.2007.10.023 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 260HQ UT WOS:000253001800024 PM 18054822 ER PT J AU Iams, JD Romero, R Culhane, JF Goldenberg, RL AF Iams, Jay D. Romero, Roberto Culhane, Jennifer F. Goldenberg, Robert L. TI Preterm birth 2 - Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth SO LANCET LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; HIGH-RISK PREGNANCIES; CERVICAL INTRAEPITHELIAL NEOPLASIA; FISH-OIL SUPPLEMENTATION; ABNORMAL VAGINAL FLORA; LOW-DOSE ASPIRIN; BACTERIAL VAGINOSIS; PERIODONTAL-DISEASE; CERCLAGE TRIAL AB Interventions to reduce the morbidity and mortality of preterm birth can be primary (directed to all women), secondary (aimed at eliminating or reducing existing risk), or tertiary (intended to improve outcomes for preterm infants). Most efforts so far have been tertiary interventions, such as regionalised care, and treatment with antenatal corticosteroids, tocolytic agents, and antibiotics. These measures have reduced perinatal morbidity and mortality; but the incidence of preterm birth is increasing. Advances in primary and secondary care, following strategies used for other complex health problems, such as cervical cancer, will be needed to prevent prematurity-related illness in infants and children. C1 [Iams, Jay D.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Culhane, Jennifer F.; Goldenberg, Robert L.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RP Iams, JD (reprint author), 1654 Upham Dr, Columbus, OH 43210 USA. EM iams.1@osu.edu NR 182 TC 191 Z9 198 U1 2 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN 12 PY 2008 VL 371 IS 9607 BP 164 EP 175 DI 10.1016/S0140-6736(08)60108-7 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 252ND UT WOS:000252452300031 PM 18191687 ER PT J AU Magnus, T Liu, Y Parker, GC Rao, MS AF Magnus, Tim Liu, Ying Parker, Graham C. Rao, Mahendra S. TI Stem cell myths SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE stem cell; homing; immortal; embryonic stem cells; adult stem cells ID MARROW STROMAL CELLS; NEURAL PROGENITOR CELLS; RAT SPINAL-CORD; PANCREATIC BETA-CELLS; AGE-RELATED-CHANGES; BONE-MARROW; ADULT-RAT; IN-VITRO; OSTEOGENESIS IMPERFECTA; DEVELOPMENTAL-CHANGES AB Stem cells, although difficult to define, hold great promise as tools for understanding development and as therapeutic agents. However, as with any new field, uncritical enthusiasm can outstrip reality. In this review, we have listed nine common myths that we believe affect our approach to evaluating stem cells for therapy. We suggest that careful consideration needs to be given to each of these issues when evaluating a particular cell for its use in therapy. Data need to be collected and reported for failed as well as successful experiments and a rigorous scientific approach taken to evaluate the undeniable promise of stem cell biology. C1 [Magnus, Tim; Liu, Ying; Rao, Mahendra S.] NIA, Stem Cell Sect, Neurosci Lab, NIH, Baltimore, MD 21224 USA. [Parker, Graham C.] Wayne State Univ, Childrens Hosp Michigan, Carman & Ann Adams Dept Pediat, Childrens Res Ctr Michigan,Sch Med, Detroit, MI 48201 USA. [Rao, Mahendra S.] Invitrogen Corp, Corp Res Labs, Carlsbad, CA 92008 USA. RP Rao, MS (reprint author), NIA, Stem Cell Sect, Neurosci Lab, NIH, 333 Cassell Dr,Room 406A, Baltimore, MD 21224 USA. EM vzeq2tcr@verizon.net NR 111 TC 10 Z9 11 U1 0 U2 6 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD JAN 12 PY 2008 VL 363 IS 1489 BP 9 EP 22 DI 10.1098/rstb.2006.2009 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 240BS UT WOS:000251562600003 PM 17284414 ER PT J AU Chadwick, EG Capparelli, EV Yogev, R Pinto, JA Robbins, B Rodman, JH Chen, J Palumbo, P Serchuck, L Smith, E Hughes, M AF Chadwick, Ellen G. Capparelli, Edmund V. Yogev, Rarn Pinto, Jorge A. Robbins, Brian Rodman, John H. Chen, Jie Palumbo, Paul Serchuck, Leslie Smith, Elizabeth Hughes, Michael CA P1030 Team TI Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week results SO AIDS LA English DT Article DE HIV-1-infected infants; lopinavir/ritonavir; pharmacokinetics ID ACTIVE ANTIRETROVIRAL THERAPY; INFECTED INFANTS; INHIBITOR; TYPE-1; HIV-1; LOAD AB Objective: To investigate pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r)-based therapy in HIV-1-infected infants 6 weeks to 6 months of age. Methods: A prospective, multicenter, open-label trial of 21 infants with HIV-1 RNA > 10000 copies/ml and treated with LPV/r 300/75 mg/m(2) twice daily plus two nucleoside reverse transcriptase inhibitors. Intensive pharmacokinetic sampling was performed at 2 weeks and predose concentrations were collected every 8 weeks; safety and plasma HIV-1 RNA were monitored every 4-12 weeks for 24 weeks. Results: Median age at enrollment was 14.7 weeks (range, 6.9-25.7) and 19/21 completed > 24 weeks of study. Although LPV/r apparent clearance was slightly higher than in older children, the median area under the concentration-time curve 0-12 h (67.5 mu g.h/ml) was in the range reported from older children taking the recommended dose of 230/57.5 mg/m(2). Predose concentrations stabilized at a higher level after the first 2 weeks of study. In as-treated analysis at week 24, 10/19 (53%) had plasma HIV-1 RNA < 400 copies/ml (median change, -3.33 log(10) copies/ml); poor adherence contributed to delayed viral suppression, which improved with longer follow-up. Three infants (14%) had transient adverse events of grade 3 or more that were possibly related to study treatment but did not require permanent treatment discontinuation. Conclusion: Despite higher clearance in infants 6 weeks to 6 months of age, a twice daily dose of 300/75 mg/m(2) LPV/r provided similar exposure to that in older children, was well tolerated and provided favorable virological and clinical efficacy. (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Chadwick, Ellen G.; Yogev, Rarn] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA. [Capparelli, Edmund V.] Univ Calif San Diego, Pediat Pharmacol Res Unit, San Diego, CA 92103 USA. [Robbins, Brian; Rodman, John H.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Chen, Jie; Hughes, Michael] Harvard Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA USA. [Palumbo, Paul] Dartmouth Hitchcock Med Ctr, Div Infect Dis, Lebanon, NH 03766 USA. [Palumbo, Paul] Dartmouth Hitchcock Med Ctr, Div Int Hlth, Lebanon, NH 03766 USA. [Serchuck, Leslie] Natl Inst Hlth Bethesda, Div Pediat Adolescent & Maternal AIDS, Bethesda, MD USA. [Smith, Elizabeth] Natl Inst Hlth Bethesda, Div AIDS, Bethesda, MD USA. [Pinto, Jorge A.] Univ Fed Minas Gerais, Escola Med, Belo Horizonte, MG, Brazil. RP Chadwick, EG (reprint author), Childrens Mem Hosp, Div Infect Dis, 2300 Childrens Plaza,Box 20, Chicago, IL 60614 USA. EM egchadwick@childrensmemorial.org FU NIAID NIH HHS [U01 AI069516] NR 12 TC 50 Z9 51 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 11 PY 2008 VL 22 IS 2 BP 249 EP 255 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 251LX UT WOS:000252376100010 PM 18097227 ER PT J AU Diabate, A Dabire, RK Heidenberger, K Crawford, J Lamp, WO Culler, LE Lehmann, T AF Diabate, Abdoulaye Dabire, Roch K. Heidenberger, Kyle Crawford, Jacob Lamp, William O. Culler, Lauren E. Lehmann, Tovi TI Evidence for divergent selection between the molecular forms of Anopheles gambiae: role of predation SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID WEST-AFRICA; GENETIC DIFFERENTIATION; CHARACTER DISPLACEMENT; INCIPIENT SPECIATION; HABITAT SELECTION; CHROMOSOMAL FORM; TEMPORARY POOLS; IMMATURE STAGES; S.L. DIPTERA; DNA ANALYSIS AB Background: The molecular forms of Anopheles gambiae are undergoing speciation. They are characterized by a strong assortative mating and they display partial habitat segregation. The M form is mostly found inflooded/irrigated areas whereas the S form dominates in the surrounding areas, but the ecological factors that shape this habitat segregation are not known. Resource competition has been demonstrated between species undergoing divergent selection, but resource competition is not the only factor that can lead to divergence. Results: In a field experiment using transplantation of first instar larvae, we evaluated the role of larval predators in mediating habitat segregation between the forms. We found a significant difference in the ability of the molecular forms to exploit the different larval sites conditioned on the presence of predators. In absence of predation, the molecular forms outcompeted each other in their respective natural habitats however, the developmental success of the M form was significantly higher than that of the S form in both habitats under predator pressure. Conclusion: Our results provide the first empirical evidence for specific adaptive differences between the molecular forms and stress the role of larval predation as one of the mechanisms contributing to their divergence. C1 [Diabate, Abdoulaye; Heidenberger, Kyle; Crawford, Jacob; Lehmann, Tovi] NIAID, Natl Inst Hlth, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Diabate, Abdoulaye; Dabire, Roch K.] IRSS Ctr Muraz, Lab Parasitol Entomol, Bobo Dioulasso, Burkina Faso. [Lamp, William O.; Culler, Lauren E.] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA. RP Diabate, A (reprint author), NIAID, Natl Inst Hlth, Lab Malaria & Vector Res, 12735 Twinbrook Parkway,Room 2W13A, Rockville, MD 20852 USA. EM a_diabate@hotmail.com; dabire_roch@hotmail.com; heidenbk@lafayette.edu; jacobecrawford@gmail.com; lamp@umd.edu; leculler@gmail.com; tlehmann@niaid.nih.gov RI Lamp, William/G-6081-2015; OI Lamp, William/0000-0002-8565-1560; Culler, Lauren/0000-0003-2300-5405 FU Intramural NIH HHS NR 49 TC 55 Z9 57 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD JAN 11 PY 2008 VL 8 AR 5 DI 10.1186/1471-2148-8-5 PG 11 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 257GD UT WOS:000252786300001 PM 18190719 ER PT J AU Lee, KPK Dey, M Neculai, D Cao, C Dever, TE Sicheri, F AF Lee, Kenneth P. K. Dey, Madhusudan Neculai, Dante Cao, Chune Dever, Thomas E. Sicheri, Frank TI Structure of the dual enzyme ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing SO CELL LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM; MESSENGER-RNA; MYCOBACTERIUM-TUBERCULOSIS; CRYSTAL-STRUCTURE; TRANSMEMBRANE PROTEIN; 2-5A-DEPENDENT RNASE; KINASE-ACTIVITY; ACTIVATION; CLEAVAGE AB Ire1 is an ancient transmembrane sensor of ER stress with dual protein kinase and ribonuclease activities. In response to ER stress, Ire1 catalyzes the splicing of target mRNAs in a spliceosome-independent manner. We have determined the crystal structure of the dual catalytic region of Ire1at 2.4 angstrom resolution, revealing the fusion of a domain, which we term the KEN domain, to the protein kinase domain. Dimerization of the kinase domain composes a large catalytic surface on the KEN domain which carries out ribonuclease function. We further show that signal induced trans-autophosphorylation of the kinase domain permits unfettered binding of nucleotide, which in turn promotes dimerization to compose the ribonuclease active site. Comparison of Ire1 to a topologically disparate ribonuclease reveals the convergent evolution of their catalytic mechanism. These findings provide a basis for understanding the mechanism of action of RNaseL and other pseudokinases, which represent 10% of the human kinome. C1 [Lee, Kenneth P. K.; Sicheri, Frank] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Syst Biol, Toronto, ON M5G 1X5, Canada. [Lee, Kenneth P. K.; Neculai, Dante; Sicheri, Frank] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada. [Dey, Madhusudan; Cao, Chune; Dever, Thomas E.] Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Sicheri, F (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Syst Biol, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. EM sicheri@mshri.on.ca RI Neculai, Dante/A-9923-2011; Sicheri, Frank/F-8856-2013; Neculai, Dante/M-2884-2013; OI Dever, Thomas/0000-0001-7120-9678 FU Intramural NIH HHS [Z01 HD001010-13] NR 41 TC 138 Z9 143 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 11 PY 2008 VL 132 IS 1 BP 89 EP 100 DI 10.1016/j.cell.2007.10.057 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 266IL UT WOS:000253427600018 PM 18191223 ER PT J AU Kang, JS Tian, JH Pan, PY Zald, P Li, C Deng, C Sheng, ZH AF Kang, Jian-Sheng Tian, Jin-Hua Pan, Ping-Yue Zald, Philip Li, Cuiling Deng, Chuxia Sheng, Zu-Hang TI Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation SO CELL LA English DT Article ID TRANSPORT; PROTEIN; MICROTUBULES; ORGANELLES; SYNAPSES; NEURONS; MILTON; TRANSMISSION; POTENTIATION; CYTOSKELETON AB Proper distribution of mitochondria within axons and at synapses is critical for neuronal function. While one-third of axonal mitochondria are mobile, a large proportion remains in a stationary phase. However, the mechanisms controlling mitochondrial docking within axons remain elusive. Here, we report a role for axon-targeted syntaphilin (SNPH) in mitochondrial docking through its interaction with microtubules. Axonal mitochondria that contain exogenously or endogenously expressed SNPH lose mobility. Deletion of the mouse snph gene results in a substantially higher proportion of axonal mitochondria in the mobile state and reduces the density of mitochondria in axons. The snph mutant neurons exhibit enhanced short-term facilitation during prolonged stimulation, probably by affecting calcium signaling at presynaptic boutons. This phenotype is fully rescued by reintroducing the snph gene into the mutant neurons. These findings demonstrate a molecular mechanism for controlling mitochondrial docking in axons that has a physiological impact on synaptic function. C1 [Kang, Jian-Sheng; Tian, Jin-Hua; Pan, Ping-Yue; Zald, Philip; Sheng, Zu-Hang] NINDS, NIH, Porter Neurosci Res Ctr, Synapt Funct Sect, Bethesda, MD 20892 USA. [Pan, Ping-Yue] Shanghai Jiao Tong Univ, Sch Med, Dept Neurobiol, Shanghai 200030, Peoples R China. [Li, Cuiling; Deng, Chuxia] NIDDK, NIH, Genet Dev & Dis Branch, Mammalian Genet Sect, Bethesda, MD 20892 USA. RP Sheng, ZH (reprint author), NINDS, NIH, Porter Neurosci Res Ctr, Synapt Funct Sect, Bldg 35,Rm 4B203, Bethesda, MD 20892 USA. EM shengz@ninds.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS [Z01 NS002946-11] NR 43 TC 184 Z9 187 U1 0 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 11 PY 2008 VL 132 IS 1 BP 137 EP 148 DI 10.1016/j.cell.2007.11.024 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 266IL UT WOS:000253427600022 PM 18191227 ER PT J AU Keyes, KM Grant, BF Hasin, DS AF Keyes, Katherine M. Grant, Bridget F. Hasin, Deborah S. TI Evidence for a closing gender gap in alcohol use, abuse, and dependence in the United States population SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE gender; birth cohort; alcohol abuse and dependence ID DSM-IV ALCOHOL; INTERVIEW SCHEDULE AUDADIS; NATIONAL EPIDEMIOLOGIC SURVEY; USE DISORDER CRITERIA; DRUG-USE; GENERAL-POPULATION; SEX-DIFFERENCES; COMORBIDITY SURVEY; DRINKING BEHAVIOR; BIRTH COHORT AB Background: Descriptively, male-female differences in alcohol consumption and alcohol use disorders appear to have decreased in birth cohorts reaching adulthood since the 1970s compared to earlier birth cohorts. However, such birth cohort effects on gender differences have never been statistically tested in nationally representative data. The aim of this study was to test the hypothesis that gender differences in alcohol consumption, abuse, and dependence are decreasing over time. Methods: Face-to-face survey conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions among those aged <90 (N=42,693). Birth cohort was divided into four categories: 1913-1932, 1933-1949, 1950-1967, 1968-1984. Outcomes included lifetime largest drinks, frequent binge drinking, DSM-IV defined alcohol abuse, and alcohol dependence, measured with the Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS-IV). Findings: Birth cohort and gender interacted significantly in predicting lifetime largest drinks (F=27.6, [d.f.=3], p<0.0001), frequent binge drinking (F=40.0, [d.f. = 3], p < 0.0001), alcohol abuse (F= 62.0, [d.f. = 3], p < 0.0001) and alcohol dependence (F = 15.3, [d.f. = 3], p < 0.0001). Cohort-specific ORs indicated monotonic decreases in the gender ratio in more recent birth cohorts for all outcomes. Conclusion: These results suggest that gender differences in the prevalence of all four outcomes are decreasing in younger age cohorts. While these changes are consistent with a cohort effect, the possibility of age and period effects cannot be ruled out but suggest important avenues for more specific hypothesis testing. Further, women in younger cohorts may be in need of new targeted prevention and intervention efforts. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Keyes, Katherine M.; Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Keyes, Katherine M.; Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hasin, Deborah S.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Hasin, DS (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr,123, New York, NY 10032 USA. EM dsh2@columbia.edu FU Intramural NIH HHS; NIAAA NIH HHS [K05 AA014223, K05 AA014223-01]; NIDA NIH HHS [R01 DA018652, R01 DA018652-05] NR 72 TC 171 Z9 172 U1 7 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 11 PY 2008 VL 93 IS 1-2 BP 21 EP 29 DI 10.1016/j.drugalcdep.2007.08.017 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 260SW UT WOS:000253031700003 PM 17980512 ER PT J AU Kahler, CW Strong, DR Papandonatos, GD Colby, SM Clark, MA Boergers, J Niaura, R Abrams, DB Buka, SL AF Kahler, Christopher W. Strong, David R. Papandonatos, George D. Colby, Suzanne M. Clark, Melissa A. Boergers, Julie Niaura, Raymond Abrams, David B. Buka, Stephen L. TI Cigarette smoking and the lifetime alcohol involvement continuum SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE alcohol; alcohol use disorders; smoking; tobacco; item response modeling; Rasch model ID NATIONAL EPIDEMIOLOGIC SURVEY; RASCH MODEL ANALYSIS; TOBACCO USE; DSM-IV; COLLEGE-STUDENTS; NICOTINE DEPENDENCE; USE DISORDERS; RISK; CONSUMPTION; CESSATION AB Greater understanding of how alcohol use relates to the initiation, progression, and persistence of cigarette smoking is of great significance for efforts to prevent and treat smoking and excessive drinking and their substantial combined iatrogenic effects on health. Studies investigating the relationship between levels of alcohol involvement and smoking have typically been limited by analytic approaches that treat drinking behavior and alcohol use disorder diagnoses as separate phenomena rather than as indicators of a single latent alcohol involvement dimension. The purposes of the present study were (a) to create a lifetime index of alcohol involvement that integrates information about alcohol consumption and alcohol problems into a single measure and (b) to relate this index to initiation of smoking, progression from initiation to daily smoking, progression from initiation to dependence, and persistence of smoking. Rasch model analyses of data from 1508 middle-aged (34-44 years) adults showed that creating an additive index of lifetime alcohol involvement was psychometrically supported. Significant quadratic effects of alcohol involvement on initiation, progression, and persistence of smoking demonstrated that there were specific regions of the alcohol involvement continuum that were particularly strongly related to increased smoking. These results provide the most comprehensive depiction to date of the nature of the relationship between lifetime alcohol involvement and lifetime cigarette smoking and suggest potential avenues for research on the etiology and maintenance of smoking and tobacco dependence. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Kahler, Christopher W.; Colby, Suzanne M.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Strong, David R.; Niaura, Raymond] Butler Hosp, Providence, RI 02906 USA. [Strong, David R.; Niaura, Raymond] Brown Univ, Warren Alpert Med Sch, Providence, RI 02906 USA. [Papandonatos, George D.] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. [Clark, Melissa A.] Brown Univ, Ctr Gerontol & Hlth Care Res, Providence, RI 02912 USA. [Boergers, Julie] Rhode Isl Hosp, Providence, RI 02903 USA. [Boergers, Julie] Brown Univ, Warren Alpert Med Sch, Providence, RI 02903 USA. [Abrams, David B.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Buka, Stephen L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. RP Kahler, CW (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box G-S121-5, Providence, RI 02912 USA. EM Christopher_Kahler@brown.edu RI Buka, Stephen/H-7335-2014; Papandonatos, George/J-2328-2014; OI Buka, Stephen/0000-0002-8578-9308; Papandonatos, George/0000-0001-6770-932X FU NCI NIH HHS [P50 CA084719-05, P50 CA084719, P50 CA084719-06, P50 CA084719-07, P50 CA084719-08, P50 CA084719-10] NR 60 TC 48 Z9 49 U1 4 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 11 PY 2008 VL 93 IS 1-2 BP 111 EP 120 DI 10.1016/j.drugalcdep.2007.09.004 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 260SW UT WOS:000253031700013 PM 17964082 ER PT J AU Somoza, E Somoza, P Lewis, D Li, SH Winhusen, T Chiang, N Vocci, F Horn, P Elkashef, A AF Somoza, Eugene Somoza, Peggy Lewis, Daniel Li, Shou-Hua Winhusen, Theresa Chiang, Nora Vocci, Frank Horn, Paul Elkashef, Ahmed TI The SRPHK1 outcome measure for cocaine-dependence trials combines self-report, urine benzoylecgonine levels, and the concordance between the two to determine a cocaine-use status for each study day SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE outcome measures; cocaine dependence; clinical trials; urine toxicology; SRPHK1 ID LONGITUDINAL DATA-ANALYSIS; PLACEBO-CONTROLLED TRIAL; CLINICAL-TRIALS; DOUBLE-BLIND; EXCRETION; HUMANS; MEDICATIONS; URINALYSIS AB Background: There is currently no FDA-approved medication for cocaine dependence and no standard primary outcome measure for reduction of cocaine use in cocaine-dependence trials. The ability to detect a significant medication effect will depend, in part, on the primary outcome measure utilized. The goal of the present paper is to compare self-report or either of two urine toxicology measures used alone to a relatively new measure - the SRPHK1 - which combines self-report, quantitative urine benzoylecgonine levels, and an estimate of the concordance between the two to determine the cocaine-use status of each study day. Method: Datasets from two separate randomized, placebo-controlled cocaine-dependence trials were used to compare four cocaine-use outcome measures. Results: The two data sets yielded very similar findings and suggest that the combined measure is associated with significantly fewer missing data than urine toxicology and that estimated cocaine use varied significantly depending on which measure was used, with the lowest use estimate being yielded by self-report, the highest by the two urine toxicology measures evaluated, and an intermediate value obtained using the combined measure. The results also suggest that the concordance between self-report and urine toxicology is around 90% at the beginning of the clinical trial but decreases to around 75% by the end of the trial. Conclusion: By combining the objectivity of urine toxicology with the reduced incidence of missing data characteristic of self-report, the SRPHK1 may provide advantages over self-report or urine toxicology measures used alone. In any case, the SRPHK1 provides an interesting complement to these other outcome measures and may warrant further evaluation. (c) 2007 Published by Elsevier Ireland Ltd. C1 [Somoza, Eugene; Somoza, Peggy; Lewis, Daniel; Winhusen, Theresa] Cincinnati Addict Res Ctr, Cincinnati, OH 45220 USA. [Somoza, Eugene; Winhusen, Theresa] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. [Somoza, Eugene] Vet Affairs Med Ctr, VISN 10, Cincinnati, OH 45220 USA. [Li, Shou-Hua; Chiang, Nora; Vocci, Frank; Elkashef, Ahmed] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. [Horn, Paul] Univ Cincinnati, Dept Math, Cincinnati, OH 45221 USA. RP Somoza, E (reprint author), Cincinnati Addict Res Ctr, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM somoza@uc.edu OI Winhusen, Theresa/0000-0002-3364-0739 NR 25 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 11 PY 2008 VL 93 IS 1-2 BP 132 EP 140 DI 10.1016/j.drugalcdep.2007.09.007 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 260SW UT WOS:000253031700015 PM 18029115 ER PT J AU Forgacs, E Cartwright, S Sakamoto, T Sellers, JR Corrie, JET Webb, MR White, HD AF Forgacs, Eva Cartwright, Suzanne Sakamoto, Takeshi Sellers, James R. Corrie, John E. T. Webb, Martin R. White, Howard D. TI Kinetics of ADP dissociation from the trail and lead heads of actomyosin V following the power stroke SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOSIN-V; PROCESSIVE MYOSIN; WORKING STROKE; NECK LENGTH; ACTIN; MOTOR; MECHANISM; BINDING; COORDINATION; CONSTRUCT AB Myosin V is a cellular motor protein, which transports cargos along actin filaments. It moves processively by 36-nm steps that require at least one of the two heads to be tightly bound to actin throughout the catalytic cycle. To elucidate the kinetic mechanism of processivity, we measured the rate of product release from the double-headed myosin V-HMM using a new ATP analogue, 3'-(7-diethylaminocoumarin-3-carbonylamino)-3'-deoxy-ATP (deac-aminoATP), which undergoes a 20-fold increase in fluorescence emission intensity when bound to the active site of myosin V (Forgacs, E., Cartwright, S., Kovacs, M., Sakamoto, T., Sellers, J. R., Corrie, J. E. T., Webb, M. R., and White, H. D. ( 2006) Biochemistry 45, 13035-13045). The kinetics of ADP and deac-aminoADP dissociation from actomyosin V-HMM, following the power stroke, were determined using double-mixing stopped-flow fluorescence. These used either deac-aminoATP as the substrate with ADP or ATP chase or alternatively ATP as the substrate with either a deac-aminoADP or deac-aminoATP chase. Both sets of experiments show that the observed rate of ADP or deac-aminoADP dissociation from the trail head of actomyosin V-HMM is the same as from actomyosin V-S1. The dissociation of ADP from the lead head is decreased by up to 250-fold. C1 [Forgacs, Eva; Cartwright, Suzanne; White, Howard D.] Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA. [Corrie, John E. T.; Webb, Martin R.] Natl Inst Med Res, MRC, London NW7 1AA, England. [Sakamoto, Takeshi; Sellers, James R.] NHLBI, Natl Inst Hlth, Lab Mol Physiol, Bethesda, MD 20892 USA. RP White, HD (reprint author), Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA. EM whitehd@evms.edu FU Medical Research Council [MC_U117512742, MC_U117532185]; NIBIB NIH HHS [EB00209] NR 30 TC 30 Z9 31 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 11 PY 2008 VL 283 IS 2 BP 766 EP 773 DI 10.1074/jbc.M704313200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248CE UT WOS:000252128100015 PM 17965414 ER PT J AU Zhuravleva, MA Trandem, K Sun, PD AF Zhuravleva, Marina A. Trandem, Kathryn Sun, Peter D. TI Structural implications of Siglec-5-mediated sialoglycan recognition SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Siglec-5 inhibitory receptor; two-domain structure; alpha(2,3)sialyllactose; alpha(2,6)-sialyllactose; carbohydrate specificity ID MYELIN-ASSOCIATED GLYCOPROTEIN; IMMUNOGLOBULIN-LIKE LECTINS; ACID-DEPENDENT LIGAND; I-TYPE LECTINS; SIGLEC FAMILY; MOLECULAR REPLACEMENT; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; INNATE IMMUNITY; CELL-RECEPTOR AB Sialic acid (Sia) Ig-like binding lectins are important mediators of recognition and signaling events among myeloid cells. To investigate the molecular mechanism underlying sialic acid Ig-like lectin (Siglec) functions, we determined the crystal structure of the two N-terminal extracellular domains of human myeloid cell inhibitory receptor Siglec-5 (CD170) and its complexes with two sialylated carbohydrates. The native structure revealed an unusual conformation of the CC' ligand specificity loop and a unique interdomain disulfide bond. The alpha(2,3)- and alpha(2,6)sialyllactose complexed structures showed a conserved Sia recognition motif that involves both Arg124 and a portion of the G-strand in the V-set domain forming beta-sheet-like hydrogen bonds with the glycerol side chain of the Sia. Only few protein contacts to the subterminal sugars are observed and mediated by the highly variable GG' linker and CC' loop. These structural observations, in conjunction with surface plasmon resonance binding assays, provide mechanistic insights into linkage-dependent Siglec carbohydrate recognition and suggest that Siglec-5 and other CD33-related Siglec receptors are more promiscuous in sialoglycan recognition than previously understood. Published by Elsevier Ltd. C1 [Zhuravleva, Marina A.; Trandem, Kathryn; Sun, Peter D.] NIH, NIAID, Immunogenet Lab, Struct Immunol Sect, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIH, NIAID, Immunogenet Lab, Struct Immunol Sect, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov FU Intramural NIH HHS [Z01 AI000697-14] NR 51 TC 39 Z9 40 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 11 PY 2008 VL 375 IS 2 BP 437 EP 447 DI 10.1016/j.jmb.2007.10.009 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 247TN UT WOS:000252103700010 PM 18022638 ER PT J AU Billings, KS Best, RB Rutherford, TJ Clarke, J AF Billings, Kate S. Best, Robert B. Rutherford, Trevor J. Clarke, Jane TI Crosstalk between the protein surface and hydrophobic core in a core-swapped fibronectin type III domain SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein folding; side-chain dynamics; immunoglobulin; extracellular matrix; protein design ID BETA-SANDWICH PROTEINS; SIDE-CHAIN DYNAMICS; TRANSITION-STATE; ENGINEERING ANALYSIS; HYDROGEN-EXCHANGE; FOLDING PATHWAY; NMR EXPERIMENTS; HUMAN TENASCIN; CONTACT ORDER; STABILITY AB Two homologous fibronectin type III (fnIII) domains, FNfn10 (the 10th fnIII domain of human fibronectin) and TNfn3 (the third fnIII domain of human tenascin), have essentially the same backbone structure, although they share only similar to 24% sequence identity. While they share a similar folding mechanism with a common core of key residues in the folding transition state, they differ in many other physical properties. We use a chimeric protein, FNoTNc, to investigate the molecular basis for these differences. FNoTNc is a core-swapped protein, containing the "outside" (surface and loops) of FNfn10 and the hydrophobic core of TNfn3. Remarkably, FNoTNc retains the structure of the parent proteins despite the extent of redesign, allowing us to gain insight into which components of each parent protein are responsible for different aspects of its behaviour. Naively, one would expect properties that appear to depend principally on the core to be similar to TNfn3, for example, the response to mutations, folding kinetics and side-chain dynamics, while properties apparently determined by differences in the surface and loops, such as backbone dynamics, would be more like FNfn10. While this is broadly true, it is clear that there are also unexpected crosstalk effects between the core and the surface. For example, the anomalous response of FNfn10 to mutation is not solely a property of the core as we had previously suggested. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Billings, Kate S.; Clarke, Jane] Univ Cambridge, Dept Chem, MRC Ctr Prot Engn, Cambridge CB2 1EW, England. [Best, Robert B.] NIH, NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. MRC Ctr Prot Engn, Cambridge CB2 2QH, England. RP Clarke, J (reprint author), Univ Cambridge, Dept Chem, MRC Ctr Prot Engn, Lensfield Rd, Cambridge CB2 1EW, England. EM jc162@cam.ac.uk RI Best, Robert/H-7588-2016 OI Best, Robert/0000-0002-7893-3543 FU Intramural NIH HHS; Wellcome Trust [064417/Z/01/A, 064417] NR 51 TC 16 Z9 16 U1 0 U2 9 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 11 PY 2008 VL 375 IS 2 BP 560 EP 571 DI 10.1016/j.jmb.2007.10.056 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 247TN UT WOS:000252103700019 PM 18035373 ER PT J AU Kalueff, AV Ishikawa, K Griffith, AJ AF Kalueff, Allan V. Ishikawa, Kotaro Griffith, Andrew J. TI Anxiety and otovestibular disorders: Linking behavioral phenotypes in men and mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Review DE anxiety spectrum disorders; vestibular and balance disorders; animal (experimental) models; behavioral phenotyping; genetic and pharmacological models; interplay; co-morbidity; otovestibular phenotypes ID SEROTONIN REUPTAKE INHIBITORS; PHOBIC POSTURAL VERTIGO; ELEVATED PLUS-MAZE; SEVERE HEARING IMPAIRMENT; EAR HAIR-CELLS; VESTIBULAR DYSFUNCTION; INNER-EAR; BALANCE CONTROL; PANIC DISORDER; MUTANT MICE AB Human anxiety and vestibular disorders have long been known to co-occur. Paralleling human clinical and non-clinical data, mounting genetic, pharmacological and behavioral evidence confirms that animal anxiety interplays and co-exists with vestibular/balance deficits. However, relatively few animal models have addressed the nature of this relationship. This paper examines side-by-side human psychiatric and otovestibular phenotypes with animal experimentation data, and outlines future directions of translational research in this field. Discussed here are recently developed specific animal models targeting this interplay, other traditional animal tests sensitive to altered anxiety and vestibular domains, and the existing problems with translation of animal data into human phenotypes. The role of hearing deficits and their contribution to anxiety and vestibular phenotypes are also outlined. Overall, the overlap between anxiety and balance disorders emerges as an important phenomenon in both animal and clinical studies, and may contribute markedly to the complexity of behavioral and physiological phenotypes. Animal experimental models that focus on the interplay between anxiety and vestibular disorders are needed to improve our understanding of this important biomedical problem. Published by Elsevier B.V. C1 [Kalueff, Allan V.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Ishikawa, Kotaro; Griffith, Andrew J.] NIDCD, Otolaryngol Branch, NIH, Rockville, MD USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41,10 Ctr Dr MSC 1264, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS NR 159 TC 23 Z9 25 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 10 PY 2008 VL 186 IS 1 BP 1 EP 11 DI 10.1016/j.bbr.2007.07.032 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 244MG UT WOS:000251869400001 PM 17822783 ER PT J AU Boyce-Rustay, JM Janos, AL Holmes, A AF Boyce-Rustay, Janel M. Janos, Alicia L. Holmes, Andrew TI Effects of chronic swim stress on EtOH-related behaviors in C57BL/6J, DBA/2J and BALB/cByJ mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE mouse; strain; ethanol; sedation; gene; drinking; swim stress; preference; two-bottle choice ID CORTICOTROPIN-RELEASING-FACTOR; ETHANOL-INDUCED HYPOTHERMIA; VOLUNTARY ALCOHOL INTAKE; DRUG-USE DISORDERS; SOCIAL STRESS; RESTRAINT STRESS; FAMILY-HISTORY; MOUSE STRAINS; RAT LINES; CONSUMPTION AB There is a strong clinical relationship between stress and stress-related disorders and the incidence of alcohol abuse and alcoholism, and this relationship appears to be partly genetic in origin. There are marked strain differences in ethanol (EtOH)-related behaviors and reactivity to stress, but little investigation of the interaction between the two. The present study assessed the effects of chronic exposure to swim stress on EtOH-related behavior in three common inbred strains of mice, C57BL/6J, DBA/2J and BALB/cByJ. After establishing baseline (10%) EtOH self-administration in a two-bottle free choice test, mice were exposed to daily swim stress for 14 consecutive days and EtOH consumption was measured as a percent of baseline both during stress and for 10 days afterwards. A separate experiment examined the effects of 14 days of swim stress on sensitivity to the sedative/hypnotic effects of an acute injection of 4 g/kg EtOH. Results showed that stress produced a significant decrease in EtOH consumption, relative to pre-stress baseline, in DBA/2J and BALB/cByJ, but not C57BL/6J mice. By contrast, stress increased sensitivity to the sedative/hypnotic effects of EtOH in all three strains. These findings demonstrate that chronic swim stress produces reductions in EtOH self-administration in a strain-dependent manner, and that these effects may be restricted to strains with a pre-existing aversion to EtOH. Present data also demonstrates a dissociation between effects of this stressor on EtOH self-administration and sensitivity to EtOH's sedative/hypnotic effects. In conclusion, strain differences, that are likely in large part genetic in nature, modify the effects of this stressor on EtOH's effects in a behavior-specific manner. Published by Elsevier B.V. C1 [Boyce-Rustay, Janel M.; Janos, Alicia L.; Holmes, Andrew] NIAAA, Lab Integrat Neurosci, Sect Behav Sci & Genet, Rockville, MD 20852 USA. RP Boyce-Rustay, JM (reprint author), Abbott Labs, 100 Abbot Pk Rd,Abbot Pk,R4N5 AP9A L018, Abbott Pk, IL 60064 USA. EM janel.boyce-rustay@abbott.com FU Intramural NIH HHS [Z01 AA000411-04]; NIAAA NIH HHS [Z01 AA000411] NR 62 TC 23 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 10 PY 2008 VL 186 IS 1 BP 133 EP 137 DI 10.1016/j.bbr.2007.07.031 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 244MG UT WOS:000251869400017 PM 17822784 ER PT J AU Briard, E Zoghbi, SS Imaizumi, M Gourley, JP Shetty, HU Hong, J Cropley, V Fujita, M Innis, RB Pike, VW AF Briard, Emmanuelle Zoghbi, Sami S. Imaizumi, Masao Gourley, Jonathan P. Shetty, H. Umesha Hong, Jinsoo Cropley, Vanessa Fujita, Masahiro Innis, Robert B. Pike, Victor W. TI Synthesis and evaluation in monkey of two sensitive C-11-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MULTIPLE-SCLEROSIS PATIENTS; PROTEIN 18 KDA; BINDING-SITES; NEURONAL DAMAGE; PET; RADIOLIGANDS; RADIOSYNTHESIS; DERIVATIVES; MICROGLIA; TISSUE AB We sought to develop C-11-labeled ligands for sensitive imaging of brain peripheral benzodiazepine receptors (PBR) in vivo. Two aryloxyanilides with high affinity for PBR were identified and synthesized, namely, N-acetyl-N-(2-methoxycarbonylbenzyl)-2-phenoxyaniline (3, PBR01) and N-(2-methoxybenzyI)-N-(4-phenoxypyridin-3-yl)acetamide (10, PBR28). 3 was hydrolyzed to 4, which was esterified with [C-11]iodomethane to provide [C-11]3. The O-desmethyl analogue of 10 was converted into [C-11]10 with [C-11]iodomethane. [C-11]3 and [C-11]10 were each injected into monkey to assess their brain kinetics with positron emission tomography (PET). After administration of either radioligand there was moderately high brain uptake of radioactivity. Receptor blocking and displacement experiments showed that a high proportion of this radioactivity was bound specifically to PBR. In monkey and rat, 3 and 10 were rapidly metabolized by ester hydrolysis and N-debenzylation, respectively, each to a single polar radiometabolite. [C-11]3 and [C-11]10 are effective for imaging PBR in monkey brain. [C-11]10 especially warrants further evaluation in human subjects. C1 [Briard, Emmanuelle; Zoghbi, Sami S.; Imaizumi, Masao; Gourley, Jonathan P.; Shetty, H. Umesha; Hong, Jinsoo; Cropley, Vanessa; Fujita, Masahiro; Innis, Robert B.; Pike, Victor W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Pike, VW (reprint author), NIMH, NIH, Mol Imaging Branch, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM pikev@mail.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [N01MH32004] NR 63 TC 104 Z9 104 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 10 PY 2008 VL 51 IS 1 BP 17 EP 30 DI 10.1021/jm0707370 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 248BV UT WOS:000252127200003 PM 18067245 ER PT J AU Ryu, H Jin, MK Kim, SY Choi, HK Kang, SU Kang, DW Lee, J Pearce, LV Pavlyukovets, VA Morgan, MA Tran, R Toth, A Lundberg, DJ Blumberg, PM AF Ryu, HyungChul Jin, Mi-Kyoung Kim, Su Yeon Choi, Hyun-Kyung Kang, Sang-Uk Kang, Dong Wook Lee, Jeewoo Pearce, Larry V. Pavlyukovets, Vladimir A. Morgan, Matthew A. Tran, Richard Toth, Attila Lundberg, Daniel J. Blumberg, Peter M. TI Stereospecific high-affinity TRPV1 antagonists: Chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID VANILLOID RECEPTOR; CAPSAICIN; PAIN; SENSITIVITY; POTENT AB Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues were characterized as potent and stereospecific rTRPV1 antagonists. In particular, compounds 72 and 73 displayed high binding affinities, with K-i values of 4.12 and 1.83 nM and potent antagonism with Ki values of 0.58 and 5.2 nM, respectively, in rTRPV1/CHO cells. These values are comparable or more potent than those of 5-iodoRTX under the same assay conditions. A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1. C1 [Ryu, HyungChul; Jin, Mi-Kyoung; Kim, Su Yeon; Choi, Hyun-Kyung; Kang, Sang-Uk; Kang, Dong Wook; Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. [Pearce, Larry V.; Pavlyukovets, Vladimir A.; Morgan, Matthew A.; Tran, Richard; Toth, Attila; Lundberg, Daniel J.; Blumberg, Peter M.] NCI, NIH, Ctr Canc Res, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr RI Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 FU Intramural NIH HHS NR 19 TC 25 Z9 26 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 10 PY 2008 VL 51 IS 1 BP 57 EP 67 DI 10.1021/jm701049p PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 248BV UT WOS:000252127200006 PM 18072720 ER PT J AU Chong, HS Ma, X Le, T Kwamena, B Milenic, DE Brady, ED Song, HA Brechbiel, MW AF Chong, Hyun-Soon Ma, Xiang Le, Thien Kwamena, Baidoo Milenic, Diane E. Brady, Erik D. Song, Hyun A. Brechbiel, Martin W. TI Rational design and generation of a bimodal bifunctional ligand for antibody - Targeted radiation cancer therapy SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID LANTHANIDE COMPLEXES; IN-VITRO; RADIOIMMUNOTHERAPY; RADIONUCLIDES; STABILITY; DTPA; Y-90; LYMPHOMA; MODEL; ACID AB An antibody-targeted radiation therapy (radioimmunotherapy, RIT) employs a bifunctional ligand that can effectively hold a cytotoxic metal with clinically acceptable complexation kinetics and stability while being attached to a tumor-specific antibody. Clinical exploration of the therapeutic potential of RIT has been challenged by the absence of adequate ligand, a critical component for enhancing the efficacy of the cancer therapy. To address this deficiency, the bifunctional ligand C-NETA in a unique structural class possessing both a macrocyclic cavity and a flexible acyclic moiety was designed. The practical, reproducible, and readily scalable synthetic route to C-NETA was developed, and its potential as the chelator of Bi-212, Bi-213, and Lu-177 for RIT was evaluated in vitro and in vivo. C-NETA rapidly binds both Lu(III) and Bi(III), and the respective metal complexes remain extremely stable in serum for 14 days. Lu-177-C-NETA and Bi-205/6-C-NETA possess an excellent or acceptable in vivo biodistribution profile. C1 [Chong, Hyun-Soon; Ma, Xiang; Le, Thien; Song, Hyun A.] IIT, Div Chem, Biol Chem & Phys Sci Dept, Chicago, IL 60616 USA. [Kwamena, Baidoo; Milenic, Diane E.; Brady, Erik D.; Brechbiel, Martin W.] NCI, NIH, Ctr Canc Res,Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Chong, HS (reprint author), IIT, Div Chem, Biol Chem & Phys Sci Dept, Chicago, IL 60616 USA. EM chong@iit.edu FU Intramural NIH HHS [Z01 SC010051-11, Z01 SC006353-24]; NCI NIH HHS [K22CA102637, R01CA112503-01A2, K22 CA102637, R01 CA112503] NR 28 TC 22 Z9 22 U1 4 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 10 PY 2008 VL 51 IS 1 BP 118 EP 125 DI 10.1021/jm070401q PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 248BV UT WOS:000252127200011 PM 18062661 ER PT J AU Cai, LS Liow, JS Zoghbi, SS Cuevas, J Baetas, C Hong, J Shetty, HU Seneca, NM Brown, AK Gladding, R Temme, SS Herman, MM Innis, RB Pike, VW AF Cai, Lisheng Liow, Jeih-San Zoghbi, Sami S. Cuevas, Jessica Baetas, Cesar Hong, Jinsoo Shetty, H. Umesha Seneca, Nicholas M. Brown, Amira K. Gladding, Robert Temme, Sebastian S. Herman, Mary M. Innis, Robert B. Pike, Victor W. TI Synthesis and evaluation of N-methyl and S-methyl C-11-labeled 6-methylthio-2-(4 '-N,N-dimethylamino)phenylimidazo[1,2-a]pyridines as radioligands for imaging beta-amyloid plaques in Alzheimer's disease SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PITTSBURGH COMPOUND-B; IN-VIVO; BRAIN; PET; ASSOCIATION; METAANALYSIS; DERIVATIVES; RECEPTOR; THERAPY; LIGANDS AB 6-Thiolato-substituted 2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridines (RS-IMPYs; 1-4) were synthesized as candidates for labeling with carbon-11 (t(1/2) = 20.4 min) and imaging of A(beta) plaques in living human brain using positron emission tomography (PET). K-i values for binding of these ligands to Alzheimer's disease brain homogenates were measured in vitro,against tritium-labeled 6 (Pittsburgh compound B). MeS-IMPY (3, K-i = 7.93 nM) was labeled with carbon-11 at its S- or N-methyl position to give [C-11]7 or [C-11]8, respectively. After injection into rats, [C-11]7 or [C-11]8 gave moderately high brain uptakes of radioactivity followed by rapid washout to low levels. The ratio of radioactivity at maximal uptake to that at 60 min reached 18.7 for [C-11]7. [C-11]7 behaved similarly in mouse and monkey. [C-11]7 also bound selectively to A(beta) plaques in post mortem human Alzheimer's disease brain. Although rapidly metabolized in rat by N-demethylation, [C-11]7 was stable in rat brain homogenates. The ex vivo brain radiometabolites observed in rats have a peripheral origin. Overall, [C-11]7 merits further evaluation in human subjects. C1 [Cai, Lisheng; Liow, Jeih-San; Zoghbi, Sami S.; Cuevas, Jessica; Baetas, Cesar; Hong, Jinsoo; Shetty, H. Umesha; Seneca, Nicholas M.; Brown, Amira K.; Gladding, Robert; Temme, Sebastian S.; Innis, Robert B.; Pike, Victor W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Herman, Mary M.] NIMH, NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Cai, LS (reprint author), NIMH, NIH, Mol Imaging Branch, 10 Ctr Dr,Bldg 10,Room B3 C346, Bethesda, MD 20892 USA. EM cail@intra.nimh.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [N01MH32004] NR 42 TC 13 Z9 14 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 10 PY 2008 VL 51 IS 1 BP 148 EP 158 DI 10.1021/jm700970s PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 248BV UT WOS:000252127200015 PM 18078311 ER PT J AU Larkin, JD Milkevitch, M Bhat, KL Markharn, GD Brooks, BR Bock, CW AF Larkin, Joseph D. Milkevitch, Matt Bhat, Krishna L. Markharn, George D. Brooks, Bernard R. Bock, Charles W. TI Dimers of boroglycine and methylamine boronic acid: A computational comparison of the relative importance of dative versus hydrogen bonding SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Review ID GAUSSIAN-BASIS SETS; CROSS-COUPLING REACTIONS; CORRELATED MOLECULAR CALCULATIONS; POLARIZABLE CONTINUUM MODEL; DENSITY-FUNCTIONAL THEORY; MANY-ELECTRON SYSTEMS; AB-INITIO; AFFINITY-CHROMATOGRAPHY; BORIC-ACID; WAVE-FUNCTIONS AB Boronic acids are widely used in materials science, pharmacology, and the synthesis of biologically active compounds In this Article, geometrical structures and relative energies of dimers of boroglycine, H2N-CH2-B(OH)(2), and its constitutional isomer H3C-NH-B(OH)(2), were computed using second-order Moller-Plesset perturbation theory and density functional theory; Dunning-Woon correlation-consistent cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ basis sets were employed for the MP2 calculations, and the Pople 6-311++G(d,p) basis set was employed for a majority of the DFT calculations. Effects of an aqueous environment were incorporated into the results using PCM and COSMO-RS methodology. The lowest-energy conformer of the H2N-CH2-B(OH)(2) dimer was a six-membered ring structure (chair conformation; C-i symmetry) with two intermolecular B:N dative-bonds; it was 14.0 kcal/mol lower in energy at the MP2/aug-cc-pVDZ computational level than a conformer with the classic eight-centered ring structure (C-i symmetry) in which the boroglycine monomers are linked by a pair of H-O center dot center dot center dot H bonds. Compared to the results of MP2 calculations with correlation-consistent basis sets, DFT calculations using the PBE1PBE and TPSS functionals with the 6-311++G(d,p) basis set were significantly better at predicting relative conformational energies of the H2N-CH2-B(OH)(2) and H3C-NH-B(OH)(2) dimers than corresponding calculations using the BLYP, B3LYP, OLYP, and O3LYP functionals, particularly with respect to dative-bonded structures. C1 [Milkevitch, Matt; Bock, Charles W.] Philadelphia Univ, Sch Sci & Hlth, Dept Chem & Biochem, Philadelphia, PA 19144 USA. [Larkin, Joseph D.] Bloomsburg Univ Penn, Dept Chem, Bloomsburg, PA 17815 USA. [Markharn, George D.; Bock, Charles W.] Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. [Larkin, Joseph D.; Brooks, Bernard R.] NHLBI, NIH, Bethesda, MD 20851 USA. [Bhat, Krishna L.] Widener Univ, Dept Chem, Chester, PA 19011 USA. RP Bock, CW (reprint author), Philadelphia Univ, Sch Sci & Hlth, Dept Chem & Biochem, Sch House Lane & Henry Ave, Philadelphia, PA 19144 USA. EM jlarkin@bloomu.edu FU Intramural NIH HHS; NCI NIH HHS [CA06927]; NIGMS NIH HHS [GM31186] NR 124 TC 13 Z9 13 U1 3 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JAN 10 PY 2008 VL 112 IS 1 BP 125 EP 133 DI 10.1021/jp076537h PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 247ZY UT WOS:000252122300016 PM 18072757 ER PT J AU Liu, XD Sun, LG Cheng, ZQ Zhao, SP Liu, KX Wu, XH Xie, ZQ Yin, XB Luo, HH Ding, XF Fu, DB Wang, YH AF Liu, Xiao-Dong Sun, Li-Guang Cheng, Zhong-Qi Zhao, San-Ping Liu, Ke-Xin Wu, Xiao-Hong Xie, Zhou-Qing Yin, Xue-Bin Luo, Hong-Hao Ding, Xing-Fang Fu, Dong-Bo Wang, Yu-Hong TI Paleoenvironmental implications of the guano phosphatic cementation on Dongdao Island in the South China Sea SO MARINE GEOLOGY LA English DT Article DE phosphatic cementation; guano; paleoenvironment; sea level; South China Sea ID RED-FOOTED BOOBY; GEOCHEMICAL EVIDENCE; OXYGEN ISOTOPES; CENTRAL PACIFIC; ELLICE ISLANDS; LEVEL; ATOLL; ARCHIPELAGO; PHOSPHORITE; ORIGIN AB The phosphatic cement in the bioclastic sediment sequence on the northeastern shore of Dongdao Island in the South China Sea was studied and its paleoenvironmental implications discussed. Petrological characteristics and major, trace, REE element data unequivocally supported the notion that phosphatization was closely associated with avian guano decomposition and leaching, whereas carbon and oxygen isotope results further revealed that meteoric water were involved in these processes. AMS C-14 dates on the brown phosphate cements indicate that they were formed around 5700, 5000-5100 and 2900 yr BP, respectively. The multiepisodes of phosphatization very likely correspond to intermittent seabird occupation on this island-possibly reflecting Holocene sea-level oscillation and/or long term climate changes in the South China Sea that have controlled seabird habitat. The phosphate cementation, which occurs widely in tropical islands, may be another useful monitor for sea-level and/or paleoclimate changes. (c) 2007 Published by Elsevier B.V. C1 [Liu, Xiao-Dong; Sun, Li-Guang; Cheng, Zhong-Qi; Zhao, San-Ping; Xie, Zhou-Qing; Yin, Xue-Bin; Luo, Hong-Hao] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. [Cheng, Zhong-Qi] Columbia Univ, Lamont Doherty Geol Observ, Palisades, NY 10964 USA. [Liu, Ke-Xin; Ding, Xing-Fang; Fu, Dong-Bo] Peking Univ, MOE & Inst Heavy Ion Phys, Key Lab Heavy Ion Phys, Beijing 100871, Peoples R China. [Wu, Xiao-Hong] Peking Univ, Sch Archaeol & Museol, Beijing 100871, Peoples R China. [Wang, Yu-Hong] NIH, Bethesda, MD 20892 USA. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. EM slg@ustc.edu.cn NR 51 TC 7 Z9 7 U1 4 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0025-3227 J9 MAR GEOL JI Mar. Geol. PD JAN 10 PY 2008 VL 247 IS 1-2 BP 1 EP 16 DI 10.1016/j.margeo.2007.03.014 PG 16 WC Geosciences, Multidisciplinary; Oceanography SC Geology; Oceanography GA 254RU UT WOS:000252606500001 ER PT J AU Yu, WQ Gius, D Onyango, P Muldoon-Jacobs, K Karp, J Feinberg, AP Cui, HM AF Yu, Wenqiang Gius, David Onyango, Patrick Muldoon-Jacobs, Kristi Karp, Judith Feinberg, Andrew P. Cui, Hengmi TI Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA SO NATURE LA English DT Article ID HUMAN CANCER; METHYLATION; CELLS; DNA; TRANSCRIPTION; INHIBITOR; PROTEINS; IGF2 AB Tumour suppressor genes ( TSGs) inhibiting normal cellular growth are frequently silenced epigenetically in cancer(1). DNA methylation is commonly associated with TSG silencing(1), yet mutations in the DNA methylation initiation and recognition machinery in carcinogenesis are unknown(2). An intriguing possible mechanism for gene regulation involves widespread non- coding RNAs such as microRNA, Piwi- interacting RNA and antisense RNAs3-5. Widespread sense - antisense transcripts have been systematically identified in mammalian cells(6), and global transcriptome analysis shows that up to 70% of transcripts have antisense partners and that perturbation of antisense RNA can alter the expression of the sense gene(7). For example, it has been shown that an antisense transcript not naturally occurring but induced by genetic mutation leads to gene silencing and DNA methylation, causing thalassaemia in a patient(8). Here we show that many TSGs have nearby antisense RNAs, and we focus on the role of one RNA in silencing p15, a cyclin- dependent kinase inhibitor implicated in leukaemia. We found an inverse relation between p15 antisense ( p15AS) and p15 sense expression in leukaemia. A p15AS expression construct induced p15 silencing in cis and in trans through heterochromatin formation but not DNA methylation; the silencing persisted after p15AS was turned off, although methylation and heterochromatin inhibitors reversed this process. The p15AS-induced silencing was Dicer- independent. Expression of exogenous p15AS in mouse embryonic stem cells caused p15 silencing and increased growth, through heterochromatin formation, as well as DNA methylation after differentiation of the embryonic stem cells. Thus, natural antisense RNA may be a trigger for heterochromatin formation and DNA methylation in TSG silencing in tumorigenesis. C1 [Yu, Wenqiang; Onyango, Patrick; Feinberg, Andrew P.; Cui, Hengmi] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Yu, Wenqiang; Onyango, Patrick; Feinberg, Andrew P.; Cui, Hengmi] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Gius, David; Muldoon-Jacobs, Kristi] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Karp, Judith] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. RP Cui, HM (reprint author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, 720 Rutland Ave, Baltimore, MD 21205 USA. EM afeinberg@jhu.edu; hcui@jhmi.edu FU NCI NIH HHS [R37 CA054358, R37 CA054358-18] NR 22 TC 511 Z9 570 U1 13 U2 57 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 10 PY 2008 VL 451 IS 7175 BP 202 EP U10 DI 10.1038/nature06468 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 249GA UT WOS:000252214400045 PM 18185590 ER PT J AU Acharya, JK Dasgupta, U Rawat, SS Yuan, CQ Sanxaridis, PD Yonamine, I Karim, P Nagashima, K Brodsky, MH Tsunoda, S Acharya, U AF Acharya, Jairaj K. Dasgupta, Ujjaini Rawat, Satinder S. Yuan, Changqing Sanxaridis, Parthena D. Yonamine, Ikuko Karim, Pusha Nagashima, Kunio Brodsky, Michael H. Tsunoda, Susan Acharya, Usha TI Cell-nonautonomous function of ceramidase in photoreceptor homeostasis SO NEURON LA English DT Article ID RHODOPSIN-ARRESTIN COMPLEXES; DROSOPHILA-MELANOGASTER; SPHINGOSINE 1-PHOSPHATE; NEUTRAL CERAMIDASE; RETINAL DEGENERATION; VISUAL TRANSDUCTION; ENDOCYTOSIS; MEMBRANE; SPHINGOLIPIDS; APOPTOSIS AB Neutral ceramidase, a key enzyme of sphingolipid metabolism, hydrolyzes ceramide to sphingosine. These sphingolipids are critical structural components of cell membranes and act as second messengers in diverse signal transduction cascades. Here, we have isolated and characterized functional null mutants of Drosophila ceramidase. We show that secreted ceramidase functions in a cell-nonautonomous manner to maintain photoreceptor homeostasis. In the absence of ceramidase, photoreceptors degenerate in a light-dependent manner, are defective in normal endocytic turnover of rhodopsin, and do not respond to light stimulus. Consistent with a cell-nonautonomous function, overexpression of ceramidase in tissues distant from photoreceptors suppresses photoreceptor degeneration in an arrestin mutant and facilitates membrane turnover in a rhodopsin null mutant. Furthermore, our results show that secreted ceramidase is internalized and localizes to endosomes. Our findings establish a role for a secreted sphingolipid enzyme in the regulation of photoreceptor structure and function. C1 [Dasgupta, Ujjaini; Rawat, Satinder S.; Yonamine, Ikuko; Karim, Pusha; Brodsky, Michael H.; Acharya, Usha] Univ Massachusetts, Sch Med, Program Mol Med, Program Gene Funct & Express, Worcester, MA 01605 USA. [Acharya, Jairaj K.; Yuan, Changqing] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. [Sanxaridis, Parthena D.; Tsunoda, Susan] Boston Univ, Dept Biol, Boston, MA 02215 USA. [Nagashima, Kunio] SAIC, Image Anal Lab, EM Facil, Frederick, MD 21702 USA. RP Acharya, U (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, Program Gene Funct & Express, Worcester, MA 01605 USA. EM usha.acharya@umassmed.edu FU Intramural NIH HHS; NEI NIH HHS [R01EY16469, R01 EY016469-03, R01 EY016469-01, R01 EY016469, R01 EY013751, R01 EY016469-02, R01EY013751] NR 52 TC 33 Z9 33 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 10 PY 2008 VL 57 IS 1 BP 69 EP 79 DI 10.1016/j.neuron.2007.10.041 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 250YZ UT WOS:000252338600010 PM 18184565 ER PT J AU Haefner, RM Cumming, BG AF Haefner, Ralf M. Cumming, Bruce G. TI Adaptation to natural binocular disparities in primate V1 explained by a generalized energy model SO NEURON LA English DT Article ID CATS VISUAL-CORTEX; HORIZONTAL-DISPARITY; RECEPTIVE-FIELDS; COMPLEX CELLS; NEURAL MECHANISMS; MACAQUE V1; DEPTH DISCRIMINATION; OCULAR DOMINANCE; STRIATE CORTEX; NEURONS AB Sensory processing in the brain is thought to have evolved to encode naturally occurring stimuli efficiently. We report an adaptation in binocular cortical neurons that reflects the tight constraints imposed by the geometry of 3D vision. We show that the widely used binocular energy model predicts that neurons dedicate part of their dynamic range to impossible combinations of left and right images. Approximately 42% of the neurons we record from V1 of awake monkeys behave in this way (a powerful confirmation of the model), while about 58% deviate from the model in a manner that concentrates more of their dynamic range on stimuli that obey the constraints of binocular geometry. We propose a simple extension of the energy model, using multiple subunits, that explains the adaptation we observe, as well as other properties of binocular neurons that have been hard to account for, such as the response to anticorrelated stereograms. C1 [Haefner, Ralf M.; Cumming, Bruce G.] NEI, NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Haefner, RM (reprint author), NEI, NIH, Sensorimotor Res Lab, 49 Convent Dr,Bldg 49-2A50, Bethesda, MD 20892 USA. EM ralf.haefner@gmail.com RI Haefner, Ralf/C-3996-2009; OI Haefner, Ralf M/0000-0002-5031-0379 FU Intramural NIH HHS [Z01 EY000404-06] NR 46 TC 31 Z9 34 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 10 PY 2008 VL 57 IS 1 BP 147 EP 158 DI 10.1016/j.neuron.2007.10.042 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 250YZ UT WOS:000252338600016 PM 18184571 ER PT J AU Brunkhorst, FM Engel, C Bloos, F Meier-Hellmann, A Ragaller, M Weiler, N Moerer, O Gruendling, M Oppert, M Grond, S Olthoff, D Jaschinski, U John, S Rossaint, R Welte, T Schaefer, M Kern, P Kuhnt, E Kiehntopf, M Hartog, C Natanson, C Loeffler, M Reinhart, K AF Brunkhorst, Frank M. Engel, Christoph Bloos, Frank Meier-Hellmann, Andreas Ragaller, Max Weiler, Norbert Moerer, Onnen Gruendling, Matthias Oppert, Michael Grond, Stefan Olthoff, Derk Jaschinski, Ulrich John, Stefan Rossaint, Rolf Welte, Tobias Schaefer, Martin Kern, Peter Kuhnt, Evelyn Kiehntopf, Michael Hartog, Christiane Natanson, Charles Loeffler, Markus Reinhart, Konrad CA German Competence Network Sepsis TI Intensive insulin therapy and pentastarch resuscitation in severe sepsis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CRITICALLY-ILL PATIENTS; HYDROXYETHYL STARCH; RENAL-FUNCTION; CRITICAL-CARE; FAILURE; SURGERY; TRANSPLANTATION; REPLACEMENT; MULTICENTER; GELATIN AB Background: The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. Methods: In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. Results: The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, <= 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate. Conclusions: The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.). C1 [Brunkhorst, Frank M.; Bloos, Frank; Hartog, Christiane; Reinhart, Konrad] Univ Jena, Dept Anesthesiol & Intens Care Med, D-07747 Jena, Germany. [Kiehntopf, Michael] Univ Jena, Inst Clin Chem & Lab Med, D-07747 Jena, Germany. [Engel, Christoph; Loeffler, Markus] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Kuhnt, Evelyn] Univ Leipzig, Coordinat Ctr Clin Trials, Leipzig, Germany. [Meier-Hellmann, Andreas] HELIOS Klin, Dept Anesthesiol & Intens Care Med, Erfurt, Germany. [Ragaller, Max] Tech Univ Dresden, Univ Hosp, Dept Anesthesiol & Intens Care Med, Dresden, Germany. [Weiler, Norbert] Univ Hosp Schleswig Holstein, Dept Anesthesiol & Intens Care Med, Kiel, Germany. [Moerer, Onnen] Univ Goettingen, Dept Anesthesiol & Intens Care Med, Gottingen, Germany. [Gruendling, Matthias] Ernst Moritz Arndt Univ Greifswald, Dept Anesthesiol & Intens Care Med, Greifswald, Germany. [Oppert, Michael] Univ Med Ctr, Charite, Dept Nephrol & Med Intens Care, Berlin, Germany. [Grond, Stefan] Univ Halle Wittenberg, Dept Anesthesiol & Intens Care Med, Halle, Germany. [Olthoff, Derk] Univ Hosp, Dept Anesthesiol & Intens Care Med, Leipzig, Germany. [Jaschinski, Ulrich] Klinikum Augsburg, Dept Anesthesiol & Crit Care Med, Augsburg, Germany. [John, Stefan] Univ Erlangen Nurnberg, Dept Hypertens & Nephrol, Erlangen, Germany. [Rossaint, Rolf] Rhein Westfal TH Aachen, Univ Hosp Aachen, Dept Anesthesiol & Intens Care Med, Aachen, Germany. [Welte, Tobias] Otto von Guericke Univ, Dept Pulm & Crit Care Med, Magdeburg, Germany. [Welte, Tobias] Hannover Med Sch, Dept Pulm & Crit Care Med, D-30623 Hannover, Germany. [Schaefer, Martin] Staedt Klinikum Brandenburg, Dept Anesthesiol & Intens Care Med, Brandenburg, Germany. [Kern, Peter] Staedt Krankenhaus Dresden Friedrichstadt, Dept Anesthesiol & Intens Care Med, Dresden, Germany. [Natanson, Charles] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Reinhart, K (reprint author), Univ Jena, Dept Anesthesiol & Intens Care Med, Erlanger Allee 101, D-07747 Jena, Germany. EM konrad.reinhart@med.uni-jena.de RI Weiler, Norbert/E-5356-2010 NR 37 TC 1451 Z9 1561 U1 5 U2 77 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 10 PY 2008 VL 358 IS 2 BP 125 EP 139 DI 10.1056/NEJMoa070716 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 249CJ UT WOS:000252204200004 PM 18184958 ER PT J AU Sheehan, KM Gulmann, C Eichler, GS Weinstein, JN Barrett, HL Kay, EW Conroy, RM Liotta, LA Petricoin, EF AF Sheehan, K. M. Gulmann, C. Eichler, G. S. Weinstein, J. N. Barrett, H. L. Kay, E. W. Conroy, R. M. Liotta, L. A. Petricoin, E. F., III TI Signal pathway pro. ling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition SO ONCOGENE LA English DT Article DE proteomics; protein microarray; colon cancer; stroma; microdissection ID PHASE PROTEIN MICROARRAYS; LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PROFILES; TUMOR MICROENVIRONMENT; TISSUE INHIBITORS; CANCER-CELLS; PROGRESSION; METASTASIS; FIBROBLASTS; INVASION AB Molecular crosstalk, including reciprocal stimulation, is theorized to take place between epithelial cancer cells and surrounding non-neoplastic stromal cells. This is the rationale for stromal therapy, which could eliminate support of a cancer by its genetically stable stroma. Epithelial-stromal crosstalk is so far poorly documented in vivo, and cell cultures and animal experiments may not provide accurate models. The current study details stromal-epithelial signalling pathways in 35 human colon cancers, and compares them with matched normal tissues using quantitative proteomic microarrays. Lysates prepared from separately microdissected epithelium and stroma were analysed using antibodies against 61 cell signalling proteins, most of which recognize activated phospho-isoforms. Analyses using unsupervised and supervised statistical methods suggest that cell signalling pathway profiles in stroma and epithelium appear more similar to each other in tumours than in normal colon. This supports the concept that coordinated crosstalk occurs between epithelium and stroma in cancer and suggests epithelial-mesenchymal transition. Furthermore, the data herein suggest that it is driven by cell proliferation pathways and that, specifically, several key molecules within the mitogen-activated protein kinase pathway may play an important role. Given recent findings of epithelial-mesenchymal transition in therapy-resistant tumour epithelium, these findings could have therapeutic implications for colon cancer. C1 [Sheehan, K. M.; Gulmann, C.; Barrett, H. L.] Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. [Sheehan, K. M.; Gulmann, C.] NIH, Natl Canc Inst, Canc Res Ctr, Pathol Lab,NCI FDA Clin Proteom Program, Bethesda, MD USA. [Sheehan, K. M.; Gulmann, C.; Barrett, H. L.; Kay, E. W.] Royal Coll Surgeons Ireland, Dept Pathol, Dublin 9, Ireland. [Eichler, G. S.; Weinstein, J. N.] NIH, Natl Canc Inst, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD USA. [Conroy, R. M.] Royal Coll Surgeons Ireland, Dept Epidemiol, Dublin, Ireland. [Liotta, L. A.; Petricoin, E. F., III] George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA USA. [Petricoin, E. F., III] US FDA, NCI, Clin Proteom Program, Bethesda, MD USA. RP Gulmann, C (reprint author), Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. EM christian_gulmann@hotmail.com RI Conroy, Ronan/C-6416-2008 OI Conroy, Ronan/0000-0001-5983-8682 NR 42 TC 41 Z9 43 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 10 PY 2008 VL 27 IS 3 BP 323 EP 331 DI 10.1038/sj.onc.1210647 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 249UR UT WOS:000252256000008 PM 17621268 ER PT J AU Yan, Y Jung, YT Wu, T Kozak, CA AF Yan, Yuhe Jung, Yong T. Wu, Tiyun Kozak, Christine A. TI Role of receptor polymorphism and glycosylation in syncytium induction and host range variation of ecotropic mouse gammaretroviruses SO RETROVIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; AMINO-ACID TRANSPORTER; N-LINKED GLYCOSYLATION; CELL LINES; RETROVIRUSES; INFECTION; IDENTIFICATION; DOMAIN; ENTRY AB Background: We previously identified unusual variants of Moloney and Friend ecotropic mouse gammaretroviruses that have altered host range and are cytopathic in cells of the wild mouse species Mus dunni. Cytopathicity was attributed to different amino acid substitutions at the same critical env residue involved in receptor interaction: S82F in the Moloney variant Sp1574, and S84A in the Friend mouse leukemia virus F-S MLV. Because M. dunni cells carry a variant CAT-1 cell surface virus receptor (dCAT-1), we examined the role of this receptor variant in cytopathicity and host range. Results: We expressed dCAT-1 or mCAT-1 of NIH 3T3 origin in cells that are not normally infectible with ecotropic MLVs and evaluated the transfectants for susceptibility to virus infection and to virus-induced syncytium formation. The dCAT-1 transfectants, but not the mCAT-1 transfectants, were susceptible to virus-induced cytopathicity, and this cytopathic response was accompanied by the accumulation of unintegrated viral DNA. The dCAT-1 transfectants, however, did not also reproduce the relative resistance of M. dunni cells to Moloney MLV, and the mCAT-1 transfectants did not show the relative resistance of NIH 3T3 cells to Sp1574. Western analysis, use of glycosylation inhibitors and mutagenesis to remove receptor glycosylation sites identified a possible role for cell-specific glycosylation in the modulation of virus entry. Conclusion: Virus entry and virus-induced syncytium formation using the CAT-1 receptor are mediated by a small number of critical amino acid residues in receptor and virus Env. Virus entry is modulated by glycosylation of cellular proteins, and this effect is cell and virus-specific. C1 [Yan, Yuhe; Kozak, Christine A.] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. [Jung, Yong T.] Dankook Univ, Dept Microbiol, Cheonan 330714, South Korea. [Wu, Tiyun] NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. EM yyan@niaid.nih.gov; yjung@dku.edu; wutiyun@mail.nih.gov; ckozak@niaid.nih.gov FU Intramural NIH HHS NR 25 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 10 PY 2008 VL 5 AR 2 DI 10.1186/1742-4690-5-2 PG 11 WC Virology SC Virology GA 265HN UT WOS:000253349800001 PM 18186934 ER PT J AU Moore, SE Jalil, F Szu, SC Hahn-Zoric, M Prentice, AM Hanson, LA AF Moore, Sophie E. Jalil, Fehmida Szu, Shousun Chen Hahn-Zoric, Mirjana Prentice, Andrew M. Hanson, Lars A. TI Revaccination does not improve an observed deficit in antibody responses in Pakistani adults born of a lower birth weight SO VACCINE LA English DT Article DE vaccine responses; immune; programming; birth weight ID B CONJUGATE VACCINES; CAPSULAR POLYSACCHARIDE; BREAST-MILK; AVIDITY; VACCINATION; CHILDREN; DISEASE; IMMUNIZATION; INFANTS; ORIGINS AB We have previously shown that the generation of antibodies to a polysaccharide vaccine (Typhim Vi) is compromised in Pakistani adults born of a lower birth weight. To assess whether this represents a true B-cell-dependent deficit, we revaccinated subjects with a second dose of the same vaccine and with a polysaccharide-protein conjugate vaccine to a different polysaccharide antigen (conjugated Haemophilus influenzae type b (Nib) vaccine). Anti-Vi IgG levels remained positively correlated with birth weight (p = 0.0284) but no associations were observed between anti-Hib IgG levels and size at birth. These findings indicate that small size at birth results in a poor antibody response to vaccination with a polysaccharide antigen vaccine in adulthood, even following a second dose of the vaccine. No such association was observed in response to a polysaccharide-protein conjugate vaccine indicating an early-life programming effect on the generation of antibodies during a B-cell-dependent immune response. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Moore, Sophie E.] MRC Labs, MRC Keneba, Banjul, Gambia. [Moore, Sophie E.; Prentice, Andrew M.] London Sch Hyg & Trop Med, MRC, Int Nutr Grp, London WC1, England. [Jalil, Fehmida] King Edward Med Coll, Dept Social & Prevent Paediat, Lahore, Pakistan. [Jalil, Fehmida] Mayo Hosp, Lahore, Pakistan. [Szu, Shousun Chen] Natl Inst Hlth, Bethesda, MD 20892 USA. [Hahn-Zoric, Mirjana; Hanson, Lars A.] Univ Gothenburg, Dept Clin Immunol, Gothenburg, Sweden. RP Moore, SE (reprint author), MRC Labs, MRC Keneba, POB 273, Banjul, Gambia. EM Sophie.Moore@lshtm.ac.uk NR 25 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 10 PY 2008 VL 26 IS 2 BP 158 EP 165 DI 10.1016/j.vaccine.2007.11.007 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 261DT UT WOS:000253060000004 PM 18068877 ER PT J AU Miura, K Orcutt, AC Muratova, OV Miller, LH Saul, A Long, CA AF Miura, Kazutoyo Orcutt, Andrew C. Muratova, Olga V. Miller, Louis H. Saul, Allan Long, Carole A. TI Development and characterization of a standardized ELISA including a reference serum on each plate to detect antibodies induced by experimental malaria vaccines SO VACCINE LA English DT Article DE enzyme linked immunosorbent assay; (ELISA); antibody; vaccine development ID LINKED-IMMUNOSORBENT-ASSAY; TRANSMISSION-BLOCKING VACCINE; PLASMODIUM-FALCIPARUM MALARIA; APICAL MEMBRANE ANTIGEN-1; CLINICAL-TRIALS; IMMUNOGLOBULIN; PHASE-1; PVS25H AB Enzyme linked immunosorbent assay (ELISA) has been widely used to measure antibody titers for evaluating the immunogenicity of a vaccine. However, there is as yet no generally accepted way of expressing the ELISA results in the case of experimental vaccines, since there is usually no uniform standard. Both end point and single dilution methods have significant disadvantages. In this paper, we obtained reproducible data with fewer dilutions of samples by addition of serially diluted standard serum to each ELISA plate. Since this ELISA method gives reliable antibody titer with less labor than other methods, it can strongly support vaccine development. Published by Elsevier Ltd. C1 [Miura, Kazutoyo; Orcutt, Andrew C.; Muratova, Olga V.; Miller, Louis H.; Saul, Allan; Long, Carole A.] NIAAA, Natl Inst Hlth, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. RP Miura, K (reprint author), 12441 Parklawn Dr,Twinbrook 2,Room 107, Rockville, MD 20852 USA. EM kmiura@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU Intramural NIH HHS [Z99 AI999999] NR 18 TC 100 Z9 101 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 10 PY 2008 VL 26 IS 2 BP 193 EP 200 DI 10.1016/j.vaccine.2007.10.064 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 261DT UT WOS:000253060000008 PM 18054414 ER PT J AU Crichlow, GV Zhou, HW Hsiao, H Frederick, KB Debrosse, M Yang, Y Folta-Stogniew, EJ Chung, HJ Fan, CP De La Cruz, EM Levens, D Lolis, E Braddock, D AF Crichlow, Gregg V. Zhou, Hongwen Hsiao, Hsin-hao Frederick, Kendra B. Debrosse, Maxime Yang, Yuande Folta-Stogniew, Ewa J. Chung, Hye-Jung Fan, Chengpeng De La Cruz, Enrique M. Levens, David Lolis, Elias Braddock, Demetrios TI Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c-myc inhibition SO EMBO JOURNAL LA English DT Article DE c-myc; FBP interacting repressor; gene transcription; RRM domain; X-ray crystallography ID RNA RECOGNITION MOTIFS; HETEROGENOUS NUCLEAR RIBONUCLEOPROTEIN; SINGLE-STRANDED-RNA; STRUCTURAL BASIS; INTERACTING REPRESSOR; TRANSCRIPTION FACTOR; MOLECULAR GRAPHICS; KH DOMAINS; PROTEIN; EXPRESSION AB c-myc is essential for cell homeostasis and growth but lethal if improperly regulated. Transcription of this oncogene is governed by the counterbalancing forces of two proteins on TFIIH -the FUSE binding protein (FBP) and the FBP-interacting repressor (FIR). FBP and FIR recognize single-stranded DNA upstream of the P1 promoter, known as FUSE, and influence transcription by oppositely regulating TFIIH at the promoter site. Size exclusion chromatography coupled with light scattering reveals that an FIR dimer binds one molecule of single-stranded DNA. The crystal structure confirms that FIR binds FUSE as a dimer, and only the N-terminal RRM domain participates in nucleic acid recognition. Site-directed mutations of conserved residues in the first RRM domain reduce FIR's affinity for FUSE, while analogous mutations in the second RRM domain either destabilize the protein or have no effect on DNA binding. Oppositely oriented DNA on parallel binding sites of the FIR dimer results in spooling of a single strand of bound DNA, and suggests a mechanism for c-myc transcriptional control. C1 [Crichlow, Gregg V.; Debrosse, Maxime; Yang, Yuande; Fan, Chengpeng; Lolis, Elias] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. [Zhou, Hongwen; Hsiao, Hsin-hao; Braddock, Demetrios] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Frederick, Kendra B.; De La Cruz, Enrique M.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA. [Folta-Stogniew, Ewa J.] Yale Univ, Sch Med, WM Keck Biotechnol Res Lab, New Haven, CT 06510 USA. [Chung, Hye-Jung; Levens, David] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lolis, E (reprint author), Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. EM elias.lolis@yale.edu; demetrios.braddock@yale.edu RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU NCI NIH HHS [T32 CA009085, T32 CA09085]; NHLBI NIH HHS [N01HV28186, N01-HV-28186]; NIAID NIH HHS [R01 AI065029]; NIDA NIH HHS [P30 DA018343, 1 P30 DA018343-01]; NIGMS NIH HHS [GM071688, R01 GM071688] NR 59 TC 32 Z9 33 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 9 PY 2008 VL 27 IS 1 BP 277 EP 289 DI 10.1038/sj.emboj.7601936 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249LQ UT WOS:000252230300026 PM 18059478 ER PT J AU Morens, DM Fauci, AS AF Morens, David M. Fauci, Anthony S. TI Dengue and hemorrhagic fever - A potential threat to public health in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID SHOCK SYNDROME; PUERTO-RICO; INFECTION; TYPE-2; THAILAND; DISEASE; RISK C1 [Morens, David M.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, Bldg 31,Room 7A-03, Bethesda, MD 20892 USA. EM dmorens@niaid.nih.gov NR 22 TC 98 Z9 103 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 9 PY 2008 VL 299 IS 2 BP 214 EP 216 DI 10.1001/jama.2007.31-a PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 248UN UT WOS:000252182600023 PM 18182605 ER PT J AU Ni, WJ McNaughton, L LeMaster, DM Sinha, R Turesky, RJ AF Ni, Weijuan McNaughton, Lynn LeMaster, David M. Sinha, Rashmi Turesky, Robert J. TI Quantitation of 13 heterocyclic aromatic amines in cooked beef, pork, and chicken by liquid chromatography-electrospray ionization/tandem mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE heterocyclic aromatic amines; food mutagens; food carcinogens; LC-ESI-MS/MS ID ALPHA-CARBOLINES; GAMMA-CARBOLINES; GRILL SCRAPINGS; VARYING DEGREES; FOOD-PRODUCTS; DNA-ADDUCTS; CANCER RISK; CHO CELLS; MEAT; IDENTIFICATION AB The concentrations of heterocyclic aromatic amines (HAAs) were determined, by liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI-MS/MS), in 26 samples of beef, pork, and chicken cooked to various levels of doneness. The HAAs identified were 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-1-methylimidazo[4,5-b]quinoline, 2-amino-1-methylimidazo[4,5-g]quinoxaline (IgQx), 2-amino-3-methylimidazo[4,5-f]quinoxaline, 2-amino-1,7-dimethylimidazo[4,5-g]quinoxaline (7-MelgQx), 2-amino-3,8-dimethylimidazo[4,5-flquinoxaline, 2-amino-1,6-dimethylfuro[3,2-e]imidazo[4,5-b]pyridine, 2-amino-1,6,7-trimethylimidazo[4,5-g]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-flquinoxaline, 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-9H-pyrido[2,3-b]indole, and 2-amino-3-methyl-9H-pyrido[2,3-b]indole. The concentrations of these compounds ranged from < 0.03 to 305 parts per billion (micrograms per kilogram). PhIP was the most abundant HAA formed in very well done barbecued chicken (up to 305 mu g/kg), broiled bacon (16 mu g/kg), and pan-fried bacon (4.9 mu g/kg). 7-MelgQx was the most abundant HAA formed in very well done pan-fried beef and steak, and in beef gravy, at concentrations up to 30,mu g/kg. Several other linear tricyclic ring HAAs containing the IgQx skeleton are formed at concentrations in cooked meats that are relatively high in comparison to the concentrations of their angular tricyclic ring isomers, the latter of which are known experimental animal carcinogens and potential human carcinogens. The toxicological properties of these recently discovered IgQx derivatives warrant further investigation and assessment. C1 [Ni, Weijuan; Turesky, Robert J.] New York State Dept Hlth, Div Environm Dis Prevent, Wadsworth Ctr, Dept Hlth, Albany, NY 12201 USA. [McNaughton, Lynn; LeMaster, David M.] New York State Dept Hlth, Div Mol Med, Wadsworth Ctr, Dept Hlth, Albany, NY 12201 USA. [Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. RP Turesky, RJ (reprint author), New York State Dept Hlth, Div Environm Dis Prevent, Wadsworth Ctr, Dept Hlth, Albany, NY 12201 USA. EM rturesky@wadsworth.org NR 37 TC 42 Z9 42 U1 4 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JAN 9 PY 2008 VL 56 IS 1 BP 68 EP 78 DI 10.1021/jf072461a PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 247EF UT WOS:000252059400009 PM 18069786 ER PT J AU Colak, D Mori, T Brill, MS Pfeifer, A Falk, S Deng, CX Monteiro, R Mummery, C Sommer, L Gotz, M AF Colak, Dilek Mori, Tetsuji Brill, Monika S. Pfeifer, Alexander Falk, Sven Deng, Chuxia Monteiro, Rui Mummery, Christine Sommer, Lukas Goetz, Magdalena TI Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neural stem cells; Olig2; Dlx2; neurogenesis; oligodendrocytes; transplantation ID MOUSE SUBVENTRICULAR ZONE; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; PROGENITOR CELLS; PRECURSOR CELLS; IN-VIVO; LINEAGE COMMITMENT; OLFACTORY-BULB; BRAIN; EXPRESSION AB In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem cells and is crucial to initiate the neurogenic lineage in the adult mouse subependymal zone. Conditional deletion of Smad4 in adult neural stem cells severely impairs neurogenesis, and this is phenocopied by infusion of Noggin, an extracellular antagonist of BMP. Smad4 deletion in stem, but not progenitor cells, as well as Noggin infusion lead to an increased number of Olig2-expressing progeny that migrate to the corpus callosum and differentiate into oligodendrocytes. Transplantation experiments further verified the cell-autonomous nature of this phenotype. Thus, BMP-mediated signaling via Smad4 is required to initiate neurogenesis from adult neural stem cells and suppress the alternative fate of oligodendrogliogenesis. C1 [Colak, Dilek; Mori, Tetsuji; Brill, Monika S.; Goetz, Magdalena] Inst Stem Cell Res, Gesell Strahlung & Unweltforsch, Helmhotz Ctr Munich, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany. [Pfeifer, Alexander] Univ Bonn, Inst Pharmacol & Toxicol, D-53113 Bonn, Germany. [Falk, Sven; Sommer, Lukas] Univ Zurich, Inst Anat, CH-8057 Zurich, Switzerland. [Deng, Chuxia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Monteiro, Rui; Mummery, Christine] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands. [Brill, Monika S.; Goetz, Magdalena] Univ Munich, D-80336 Munich, Germany. RP Gotz, M (reprint author), Inst Stem Cell Res, Gesell Strahlung & Unweltforsch, Helmhotz Ctr Munich, German Res Ctr Environm Hlth, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM magdalena.goetz@gsf.de RI Monteiro, Rui/J-2544-2013; deng, chuxia/N-6713-2016 OI Monteiro, Rui/0000-0002-4223-8506; NR 67 TC 153 Z9 159 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 9 PY 2008 VL 28 IS 2 BP 434 EP 445 DI 10.1523/JNEUROSCI.4374-07.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 249QE UT WOS:000252243100013 PM 18184786 ER PT J AU Freed, WJ Chen, J Baeckman, CM Schwartz, CM Vazin, T Cai, JL Spivak, CE Lupica, CR Rao, MS Zeng, XM AF Freed, William J. Chen, Jia Baeckman, Cristina M. Schwartz, Catherine M. Vazin, Tandis Cai, Jingli Spivak, Charles E. Lupica, Carl R. Rao, Mahendra S. Zeng, Xianmin TI Gene Expression Profile of Neuronal Progenitor Cells Derived from hESCs: Activation of Chromosome 11p15.5 and Comparison to Human Dopaminergic Neurons SO PLOS ONE LA English DT Article ID EMBRYONIC STEM-CELLS; BECKWITH-WIEDEMANN-SYNDROME; SIGNATURE SEQUENCING MPSS; IN-VITRO; CONGENITAL HYPERINSULINISM; REGULATABLE LENTIVIRUS; BEHAVIORAL-CHANGES; IMPRINTED GENES; NONCODING RNA; H19 GENE AB Background. We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription. Methodology. Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined. Principal Findings. A number of genes known to be involved in the specification of dopaminergic neurons, including MSX1, CDKN1C, Pitx1 and Pitx2, as well as several novel genes not previously associated with dopaminergic differentiation, were expressed. Notably, we found that a specific region of the genome located on chromosome 11p15.5 was highly activated. This region contains several genes which have previously been associated with the function of dopaminergic neurons, including the gene for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, IGF2, and CDKN1C, which cooperates with Nurr1 in directing the differentiation of dopaminergic neurons. Other genes in this region not previously recognized as being involved in the functions of dopaminergic neurons were also activated, including H19, TSSC4, and HBG2. IGF2 and CDKN1C were also found to be highly expressed in mature human TH-positive dopamine neurons isolated from human brain samples by laser capture. Conclusions. The present data suggest that the H19-IGF2 imprinting region on chromosome 11p15.5 is involved in the process through which undifferentiated cells are specified to become neuronal precursors and/or dopaminergic neurons. C1 [Freed, William J.; Chen, Jia; Baeckman, Cristina M.; Vazin, Tandis; Spivak, Charles E.; Lupica, Carl R.; Zeng, Xianmin] NIDA, Cellular Neurobiol Res Branch, IRP, NIH,US Dept HHS, Baltimore, MD USA. [Schwartz, Catherine M.; Rao, Mahendra S.] NIH, Natl Inst Aging, Dept Hlth & Human Serv DHHS, Lab Neurosci, Intramural Res Prog, Baltimore, MD USA. [Cai, Jingli] Thomas Jefferson Univ, Farber Inst Neurosci, Philadelphia, PA USA. RP Freed, WJ (reprint author), NIDA, Cellular Neurobiol Res Branch, IRP, NIH,US Dept HHS, Baltimore, MD USA. EM wfreed@mail.nih.gov RI backman, cristina/C-1276-2013 FU NIDA; NIA; DHHS FX Research was supported by the IRPs of NIDA and NIA, NIDA, DHHS. NR 66 TC 23 Z9 24 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 9 PY 2008 VL 3 IS 1 AR e1422 DI 10.1371/journal.pone.0001422 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 366GT UT WOS:000260469400018 PM 18183302 ER PT J AU Li, M Villaruz, AE Vadyvaloo, V Sturdevant, DE Otto, M AF Li, Min Villaruz, Amer E. Vadyvaloo, Viveka Sturdevant, Daniel E. Otto, Michael TI Al-2-dependent gene regulation in Staphylococcus epidermidis SO BMC MICROBIOLOGY LA English DT Article ID AFFECTS BIOFILM FORMATION; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; VIBRIO-HARVEYI; INTERSPECIES COMMUNICATION; SENSING SYSTEM; LUXS; AUTOINDUCER-2; VIRULENCE; METABOLISM AB Background: Autoinducer 2 (AI-2), a widespread by-product of the LuxS-catalyzed S-ribosylhomocysteine cleavage reaction in the activated methyl cycle, has been suggested to serve as an intra-and interspecies signaling molecule, but in many bacteria AI-2 control of gene expression is not completely understood. Particularly, we have a lack of knowledge about AI-2 signaling in the important human pathogens Staphylococcus aureus and S. epidermidis. Results: To determine the role of LuxS and AI-2 in S. epidermidis, we analyzed genome-wide changes in gene expression in an S. epidermidis luxS mutant and after addition of AI-2 synthesized by over-expressed S. epidermidis Pfs and LuxS enzymes. Genes under AI-2 control included mostly genes involved in sugar, nucleotide, amino acid, and nitrogen metabolism, but also virulence-associated genes coding for lipase and bacterial apoptosis proteins. In addition, we demonstrate by liquid chromatography/mass-spectrometry of culture filtrates that the pro-inflammatory phenol-soluble modulin (PSM) peptides, key virulence factors of S. epidermidis, are under luxS/AI-2 control. Conclusion: Our results provide a detailed molecular basis for the role of LuxS in S. epidermidis virulence and suggest a signaling function for AI-2 in this bacterium. C1 [Li, Min; Villaruz, Amer E.; Vadyvaloo, Viveka; Otto, Michael] NIAID, Rocky Mt Lab, Natl Inst Hlth, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. [Sturdevant, Daniel E.] NIAID, Natl Inst Hlth, Rocky Mt Labs, Res Technol Branch,Genom Unit, Hamilton, MT 59840 USA. [Vadyvaloo, Viveka] NIAID, Natl Inst Hlth, Rocky Mt Labs, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Rocky Mt Lab, Natl Inst Hlth, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. EM limin2@niaid.nih.gov; avillaruz@niaid.nih.gov; vadyvaloov@niaid.nih.gov; dsturdevant@niaid.nih.gov; motto@niaid.nih.gov FU Intramural NIH HHS NR 38 TC 39 Z9 52 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD JAN 8 PY 2008 VL 8 AR 4 DI 10.1186/1471-2180-8-4 PG 9 WC Microbiology SC Microbiology GA 261XF UT WOS:000253112600001 PM 18182108 ER PT J AU Lacey, JV Ioffe, OB Ronnett, BM Rush, BB Richesson, DA Chatterjee, N Langholz, B Glass, AG Sherman, ME AF Lacey, J. V., Jr. Ioffe, O. B. Ronnett, B. M. Rush, B. B. Richesson, D. A. Chatterjee, N. Langholz, B. Glass, A. G. Sherman, M. E. TI Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan SO BRITISH JOURNAL OF CANCER LA English DT Article DE endometrial adenocarcinoma; uterine cancer; atypical hyperplasia; counter-matching; histopathology ID GYNECOLOGIC-ONCOLOGY-GROUP; NESTED CASE-CONTROL; FOLLOW-UP; BIOPSY; CANCER; ADENOCARCINOMA; CLASSIFICATION; PROGRESSION; MANAGEMENT; ACCURACY AB Classifying endometrial hyperplasia ( EH) according to the severity of glandular crowding ( simple hyperplasia ( SH) vs complex hyperplasia ( CH)) and nuclear atypia ( simple atypical hyperplasia ( SAH) vs complex atypical hyperplasia ( CAH)) should predict subsequent endometrial carcinoma risk, but data on progression are lacking. Our nested case-control study of EH progression included 138 cases, who were diagnosed with EH and then with carcinoma ( 1970 - 2003) at least 1 year ( median, 6.5 years) later, and 241 controls, who were individually matched on age, date, and follow-up duration and counter-matched on EH classification. After centralised pathology panel and medical record review, we generated rate ratios ( RRs) and 95% confidence intervals ( CIs), adjusted for treatment and repeat biopsies. With disordered proliferative endometrium ( DPEM) as the referent, AH significantly increased carcinoma risk ( RR = 14, 95% CI, 5 - 38). Risk was highest 1 - 5 years after AH ( RR = 48, 95% CI, 8 - 294), but remained elevated 5 or more years after AH ( RR = 3.5, 95% CI, 1.0 - 9.6). Progression risks for SH ( RR = 2.0, 95% CI, 0.9 - 4.5) and CH ( RR = 2.8, 95% CI, 1.0 - 7.9) were substantially lower and only slightly higher than the progression risk for DPEM. The higher progression risks for AH could foster management guidelines based on markedly different progression risks for atypical vs non-atypical EH. C1 [Lacey, J. V., Jr.; Richesson, D. A.; Sherman, M. E.] Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD 20852 USA. [Ioffe, O. B.] Univ Maryland, Med Ctr, Dept Pathol, Baltimore, MD 21201 USA. [Ronnett, B. M.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD USA. [Rush, B. B.; Glass, A. G.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Chatterjee, N.] Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD USA. [Langholz, B.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. RP Lacey, JV (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd,MSC 7234, Rockville, MD 20852 USA. EM jimlacey@nih.gov FU Intramural NIH HHS NR 38 TC 49 Z9 55 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 8 PY 2008 VL 98 IS 1 BP 45 EP 53 DI 10.1038/sj.bjc.6604102 PG 9 WC Oncology SC Oncology GA 249RL UT WOS:000252247300010 PM 18026193 ER PT J AU Anderson, LA Gridley, G Engels, EA Morton, LM Cerhan, JR Cozen, W Severson, RK Davis, S Hartge, P Linet, MS AF Anderson, L. A. Gridley, G. Engels, E. A. Morton, L. M. Cerhan, J. R. Cozen, W. Severson, R. K. Davis, S. Hartge, P. Linet, M. S. TI Antibiotic use and risk of non-Hodgkin's lymphoma: a population-based case-control study SO BRITISH JOURNAL OF CANCER LA English DT Article DE lymphoma; non-Hodgkin; antibiotics; case-control study; epidemiology ID PRESCRIPTION MEDICATIONS; UNITED-STATES; DRUG-USE; METABOLITES; INFORMATION; RECALL; CELLS AB Antibiotic use in 759 non-Hodgkin's lymphoma (NHL) patients and 589 controls was compared. Neither total antibiotic use ( odds ratio 0.7, 95% confidence interval = 0.5-1.2), nor antibiotic use by site, was associated with total NHL, or NHL subtypes. There were no trends with frequency or age at first use (P trend = 0.23 and 0.26, respectively). C1 [Anderson, L. A.; Gridley, G.; Engels, E. A.; Morton, L. M.; Hartge, P.; Linet, M. S.] NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Bethesda, MD 20892 USA. [Anderson, L. A.] NCI, Div Canc Prevent, Off Preventat Oncol, Bethesda, MD 20892 USA. [Cerhan, J. R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Cerhan, J. R.] Univ Iowa, Iowa City, IA 52242 USA. [Cozen, W.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. [Cozen, W.] Univ So Calif, Dept Pathol, Los Angeles, CA 90033 USA. [Severson, R. K.] Karmanos Canc Inst, Detroit, MI 48201 USA. [Severson, R. K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48202 USA. [Davis, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Davis, S.] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. RP Anderson, LA (reprint author), NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Room 7068, Bethesda, MD 20892 USA. EM anderles@mail.nih.gov RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X; Anderson, Lesley/0000-0002-1000-3649 FU Intramural NIH HHS; NCI NIH HHS [N01 PC065064, N01 PC067008, N01 PC067009, N01 PC067010, N01-PC-67009, N02-PC-71105] NR 22 TC 2 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 8 PY 2008 VL 98 IS 1 BP 161 EP 164 DI 10.1038/sj.bjc.6604127 PG 4 WC Oncology SC Oncology GA 249RL UT WOS:000252247300027 PM 18059393 ER PT J AU Cook, MB Zhang, Y Graubard, BI Rubertone, MV Erickson, RL McGlynn, KA AF Cook, M. B. Zhang, Y. Graubard, B. I. Rubertone, M. V. Erickson, R. L. McGlynn, K. A. TI Risk of testicular germ-cell tumours in relation to childhood physical activity SO BRITISH JOURNAL OF CANCER LA English DT Article DE testicular cancer; physical activity; case-control ID CANCER; TESTIS; TRENDS; ETIOLOGY; PROSTATE AB The US Servicemen's Testicular Tumor Environmental and Endocrine Determinants ( STEED) case-control study of testicular germ-cell tumours (TGCTs) enrolled participants and their mothers in 2002-2005. Hours of sports or vigorous childhood physical activity per week were ascertained for three time periods; 1st-5th grades, 6th-8th grades and 9th-12th grades. Son- and mother-reports were analysed separately and included 539 control son-mother pairs and 499 case son-mother pairs. Odds ratios and 95% confidence intervals were produced. The analysis of the sons' responses found no relationship between childhood physical activity and TGCT, while the mothers' analysis found an inverse association, which was solely due to nonseminoma. Future studies should seek to validate responses further using recorded information sources such as school records. C1 [Cook, M. B.; Graubard, B. I.; McGlynn, K. A.] NCI, Hormonal & Reproduct Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Zhang, Y.] Yale Univ, Sch Med, Div Environm Hlth Sci, New Haven, CT 06510 USA. [Rubertone, M. V.] USA, Ctr Hlth Promot & Prevent Med, Silver Spring, MD 21010 USA. [Erickson, R. L.] Walter Reed Army Inst Res, Silver Spring, MD 20814 USA. RP Cook, MB (reprint author), NCI, Hormonal & Reproduct Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, EPS-5005,6120 Execut Blvd, Bethesda, MD 20892 USA. EM cookmich@mail.nih.gov RI Cook, Michael/A-5641-2009 OI Cook, Michael/0000-0002-0533-7302 FU Intramural NIH HHS [ZIA CP010126-15] NR 18 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 8 PY 2008 VL 98 IS 1 BP 174 EP 178 DI 10.1038/sj.bjc.6604109 PG 5 WC Oncology SC Oncology GA 249RL UT WOS:000252247300031 PM 18026189 ER PT J AU Raman, B Stopfer, M AF Raman, Baranidharan Stopfer, Mark TI Olfactory coding: Non-linear amplification separates smells SO CURRENT BIOLOGY LA English DT Editorial Material ID DROSOPHILA ANTENNAL LOBE; ODOR REPRESENTATIONS; ADAPTATION; NEURONS; SYSTEM C1 [Raman, Baranidharan; Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA. RP Stopfer, M (reprint author), NICHHD, NIH, 35 Lincoln Dr, Bethesda, MD 20892 USA. EM stopferm@mail.nih.gov NR 16 TC 2 Z9 2 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 8 PY 2008 VL 18 IS 1 BP R29 EP R32 DI 10.1016/j.cub.2007.10.063 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 250IE UT WOS:000252292400015 PM 18177710 ER PT J AU Witt, KL Livanos, E Kissling, GE Torous, DK Caspary, W Tice, RR Recio, L AF Witt, Kristine L. Livanos, Elizabeth Kissling, Grace E. Torous, Dorothea K. Caspary, William Tice, Raymond R. Recio, Leslie TI Comparison of flow cytometry- and microscopy-based methods for measuring micronucleated reticulocyte frequencies in rodents treated with nongenotoxic and genotoxic chemicals SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE mice; rats; micronucleus; chromosome damage; genotoxicity; cyclophosphamide; vincristine sulfate ID PERIPHERAL-BLOOD RETICULOCYTES; CENTER-DOT-MMS; BONE-MARROW; CYTOGENETIC DAMAGE; HUMAN CARCINOGENS; ASSAY; ERYTHROCYTES; RAT; INDUCTION; TOXICITY AB The development of automated flow cytometric (FCM) methods for evaluating micronucleus (MN) frequencies in erythrocytes has great potential for improving the sensitivity, reproducibility, and throughput of the traditional in vivo rodent MN assay that uses microscopy-based methods for data collection. Although some validation studies of the FCM evaluation methods have been performed, a comprehensive comparison of these two data collection methods under routine testing conditions with a variety of compounds in multiple species has not been conducted. Therefore, to determine if FCM evaluation of MN frequencies in rodents was an acceptable alternative to traditional manual scoring methods in our laboratory, we conducted a comparative evaluation of MN-reticulocyte (MN-RET) frequencies determined by FCM- and microscopy-based scoring of peripheral blood and bone marrow samples from B6C3F1 mice and Fisher 344 rats. Four known inducers of MN (cyclophosphamide, ethyl methanesulfonate, vincristine sulfate, acrylamide) were assayed in bone marrow and peripheral blood of both mice and rats. In addition, MN-RET frequencies were measured in bone marrow (microscopy) and peripheral blood (FCM) of mice treated with five nongenotoxic chemicals (S-adenosylmethionine chloride, cefuroxime, diphenolic acid, 3-amino-6-methylphenol, pentabromodiphenyl oxide). No significant differences were observed between results obtained by the two methods in either species. These results support the use of FCM for determining MN-RET frequency in rodents after chemical exposure. (C) 2007 Elsevier B.V. All rights reserved. C1 [Witt, Kristine L.; Caspary, William] NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Livanos, Elizabeth; Tice, Raymond R.; Recio, Leslie] Integrated Lab Syst Inc, Genet & Cellular Toxicol Program, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Torous, Dorothea K.] Litron Labs, Rochester, NY 14623 USA. RP Witt, KL (reprint author), NIEHS, Environm Toxicol Program, NIH, POB 12233,Mail Drop EC-32, Res Triangle Pk, NC 27709 USA. EM witt@niehs.nih.gov FU NIEHS NIH HHS [N01ES35514, N01 ES035514, N01 ES 35514] NR 39 TC 50 Z9 59 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JAN 8 PY 2008 VL 649 IS 1-2 BP 101 EP 113 DI 10.1016/j.mrgentox.2007.08.004 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 257JS UT WOS:000252795800012 PM 17869571 ER PT J AU Di Lello, P Jenkins, LMM Mas, C Langlois, C Malitskaya, E Fradet-Turcotte, A Archambault, J Legault, P Omichinski, JG AF Di Lello, Paola Jenkins, Lisa M. Miller Mas, Caroline Langlois, Chantal Malitskaya, Elena Fradet-Turcotte, Amelie Archambault, Jacques Legault, Pascale Omichinski, James G. TI P53 and TFIIE alpha share a common binding site on the Tfb1/p62 subunit of TFIIH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NMR; phosphatidylinositol 5-phosphate; transcription regulation; activation domains; isothermal titration calorimetry ID RNA-POLYMERASE-II; C-TERMINAL DOMAIN; PROTEIN STRUCTURES; ACTIVATION DOMAIN; TRANSCRIPTION; NMR; PHOSPHORYLATION; COMPLEX; ELONGATION; IDENTIFICATION AB The general transcription factor IN is recruited to the transcription preinitiation complex through an interaction between its p62/Tfb1 subunit and the a-subunit of the general transcription factor HE (TFIIE alpha). We have determined that the acidic carboxyl terminus of TFIIEa (TFIIE alpha(336-439)) directly binds the amino-terminal PH domain of p62/Tfb1 with nanomolar affinity. NMR mapping and mutagenesis studies demonstrate that the TFIIEa binding site on p62/Tfb1 is identical to the binding site for the second transactivation domain of p53 (p53 TAD2). In addition, we demonstrate that TFIIE alpha(336-439) is capable of competing with p53 for a common binding site on p62/ Tfb1 and that TFIIE alpha(336-439) and the diphosphorylated form (pS46/ pT55) of p53 TAD2 have similar binding constants. NMR structural studies reveal that TFIIE alpha(336-439) contains a small domain (residues 395-433) folded in a novel beta beta alpha alpha alpha topology. NMR mapping studies demonstrate that two unstructured regions (residues 377-393 and residues 433-439) located on either side of the folded domain appear to be required for TFIIE alpha(336-439) binding to p62/Tfb1 and that these two unstructured regions are held close to each other in three-dimensional space by the novel structured domain. We also demonstrate that, like p53, TFIIE alpha(336-439) can activate transcription in vivo. These results point to an important interplay between the general transcription factor TFIIEa and the tumor suppressor protein p53 in regulating transcriptional activation that may be modulated by the phosphorylation status of p53. C1 [Di Lello, Paola; Mas, Caroline; Langlois, Chantal; Malitskaya, Elena; Legault, Pascale; Omichinski, James G.] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. [Jenkins, Lisa M. Miller] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Fradet-Turcotte, Amelie; Archambault, Jacques] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. RP Omichinski, JG (reprint author), Univ Montreal, Dept Biochim, CP 6128 Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada. EM jg.omichinski@umontreal.ca RI di lello, paola/C-8605-2013 NR 37 TC 28 Z9 28 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 8 PY 2008 VL 105 IS 1 BP 106 EP 111 DI 10.1073/pnas.0707892105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 252GP UT WOS:000252435300023 PM 18160537 ER PT J AU Ebert, AM McAnelly, CA Srinivasan, A Linker, JL Horne, WA Garrity, DM AF Ebert, A. M. McAnelly, C. A. Srinivasan, A. Linker, J. L. Horne, W. A. Garrity, D. M. TI Ca2+ channel-independent requirement for MAGUK family CACNB4 genes in initiation of zebrafish epiboly SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta 4 subunit; yolk syncytial layer; nocodazole ID BETA-SUBUNIT; MIDBLASTULA TRANSITION; VERTEBRATE DEVELOPMENT; ENVELOPING LAYER; MATERNAL CONTROL; CELL; DROSOPHILA; GASTRULATION; MUTANTS; PROTEIN AB CACNB genes encode membrane-associated guanylate kinase (MAGUK) proteins once thought to function exclusively as auxiliary P subunits in assembly and gating of voltage-gated Ca2+ channels. Here, we report that zygotic deficiency of zebrafish beta 4 protein blocks initiation of epiboly, the first morphogenetic movement of teleost embryos. Reduced 134 function in the yolk syncytial layer (YSL) leads to abnormal division and dispersal of yolk syncytial nuclei, blastoderm retraction, and death, effects highly similar to microtubule disruption by nocodazole. Epiboly is restored by coinjection of human 134 cRNA or, surprisingly, by mutant cRNA encoding 134 subunits incapable of binding to Ca2+ channel alpha 1 subunits. This study defines a YSL-driven zygotic mechanism essential for epiboly initiation and reveals a Ca2+ channel-independent beta 4 protein function potentially involving the cytoskeleton. C1 [Linker, J. L.; Horne, W. A.] Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA. [Ebert, A. M.; McAnelly, C. A.; Garrity, D. M.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. [Srinivasan, A.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Horne, WA (reprint author), Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA. EM wah27@cornell.edu FU NINDS NIH HHS [R01 NS042600, NS42600] NR 35 TC 19 Z9 19 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 8 PY 2008 VL 105 IS 1 BP 198 EP 203 DI 10.1073/pnas.0707948105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 252GP UT WOS:000252435300039 PM 18172207 ER PT J AU Leonard, JN Ghirlando, R Askins, J Bell, JK Margulies, DH Davies, DR Segal, DM AF Leonard, Joshua N. Ghirlando, Rodolfo Askins, Janine Bell, Jessica K. Margulies, David H. Davies, David R. Segal, David M. TI The TLR3 signaling complex forms by cooperative receptor dimerization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dsRNA; innate immunity; Toll-like receptors ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; NF-KAPPA-B; CRYSTAL-STRUCTURE; FUNCTIONAL ANALYSES; DIRECT BINDING; MAST-CELLS; RECOGNITION; ACTIVATION; DNA AB Toll-like receptors (TLRs) initiate immune responses by recognizing pathogen-associated molecules, but the molecular basis for recognition is poorly understood. in particular, it is unclear how receptor-ligand interactions lead to the initiation of downstream signaling. Here, we describe the mechanism by which TLR3 recognizes its ligand, double-stranded RNA (dsRNA), and forms an active signaling complex. We show that dsRNA binds saturably, specifically, and reversibly to a defined ligand-binding site (or sites) on the TLR3 ectodomain (TLR3ecd). Binding affinities increase with both buffer acidity and ligand size. Purified TLR3ecd protein is exclusively monomeric in solution, but through a highly coopera tive process, it forms dimers when bound to dsRNA, and multiple TLR3ecd dimers bind to long dsRNA strands. The smallest dsRNA oligonucleotides that form stable complexes with TLR3ecd (40-50 bp) each bind one TLR3ecd dinner, and these are also the smallest oligonucleotides that efficiently activate TLR3 in cells. We conclude that TLR3 assembles on dsRNA as stable dimers and that the minimal signaling unit is one TLR3 dimer. C1 [Margulies, David H.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Leonard, Joshua N.; Askins, Janine; Segal, David M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Ghirlando, Rodolfo; Davies, David R.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Bell, Jessica K.] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. RP Davies, DR (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM drd@niddk.nih.gov; dave_segal@nih.gov RI Ghirlando, Rodolfo/A-8880-2009; Leonard, Joshua/B-7649-2009; Margulies, David/H-7089-2013; Bell, Jessica/I-3893-2013; OI Bell, Jessica/0000-0003-1455-3274; Margulies, David/0000-0001-8530-7375 FU Intramural NIH HHS; NCI NIH HHS [K22 CA122828, K22 CA122828-01A2] NR 37 TC 114 Z9 116 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 8 PY 2008 VL 105 IS 1 BP 258 EP 263 DI 10.1073/pnas.0710779105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 252GP UT WOS:000252435300049 PM 18172197 ER PT J AU Bera, TK Liu, XF Yamada, M Gavrilovat, O Mezey, E Tessarollo, L Anver, M Hahn, Y Lee, B Pastan, I AF Bera, Tapan K. Liu, Xiu-Fen Yamada, Masanori Gavrilovat, Oksana Mezey, Eva Tessarollo, Lino Anver, Miriam Hahn, Yoonsoo Lee, Byungkook Pastan, Ira TI A model for obesity and gigantism due to disruption of the Ankrd26 gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Akt signaling; coiled-coil motif; insulin resistance; hyperphagia; POTE ancestor ID LEPTIN RECEPTOR; POTE PARALOGS; ORGAN GROWTH; MICE; HYPOTHALAMUS; MELANOCORTIN; EXPRESSION; PROTEINS; PROSTATE; MUTATION AB Obesity is a major health hazard that is caused by a combination of genetic and behavioral factors. Several models of obesity have been described in mice that have defects in the production of peptide hormones, in the function of cell membrane receptors, or in a transcription factor required for neuronal cell development. We have been investigating the function of a family of genes(POTE and ANKRD26) that encode proteins that are associated with the inner aspect of the cell membrane and that contain both ankyrin repeats and spectrin helices, motifs known to interact with signaling proteins in the cell. To assess the function of ANKRD26, we prepared a mutant mouse with partial inactivation of the Ankrd26 gene. We find that the homozygous mutant mice develop extreme obesity, insulin resistance, and an increase in body size. The obesity is associated with hyperphagia with no reduction in energy expenditure and activity. The Ankrd26 protein is expressed in the arcuate and ventromedial nuclei within the hypothalamus and in the ependyma and the circumventricular organs that act as an interface between the peripheral circulation and the brain. In the enlarged hearts of the mutant mice, the levels of both phospho-Akt and mTOR were elevated. These results show that alterations in an unidentified gene can lead to obesity and identify a molecular target for the treatment of obesity. C1 [Bera, Tapan K.; Liu, Xiu-Fen; Yamada, Masanori; Hahn, Yoonsoo; Lee, Byungkook; Pastan, Ira] NCI, Mol Biol Lab, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Gavrilovat, Oksana] NIDDK, Mouse Metab Core Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Mezey, Eva] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeleta Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Canc Res Ctr, Frederick, MD 21702 USA. [Anver, Miriam] NCI, SAIC Frederick, Pathol Histotechnol Lab, Frederick, MD 21702 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Ctr Canc Res, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO12400] NR 29 TC 21 Z9 22 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 8 PY 2008 VL 105 IS 1 BP 270 EP 275 DI 10.1073/pnas.0710978105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 252GP UT WOS:000252435300051 PM 18162531 ER PT J AU Ezzelle, J Rodriguez-Chavez, IR Darden, JM Stirewalt, M Kunwar, N Hitchcock, R Walter, T D'Souza, MP AF Ezzelle, J. Rodriguez-Chavez, I. R. Darden, J. M. Stirewalt, M. Kunwar, N. Hitchcock, R. Walter, T. D'Souza, M. P. TI Guidelines on good clinical laboratory practice: Bridging operations between research and clinical research laboratories SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Review DE good clinical laboratory practice standards; GCLP; quality control; verification; review ID VACCINE TRIALS; RESPONSES; IMMUNITY; ASSAY AB A set of Good Clinical Laboratory Practice (GCLP) standards that embraces both the research and clinical aspects of GLP were developed utilizing a variety of collected regulatory and guidance material. We describe eleven core elements that constitute the GCLP standards with the objective of filling a gap for laboratory guidance, based on IND sponsor requirements, for conducting laboratory testing using specimens from human clinical trials. These GCLP standards provide guidance on implementing GLP requirements that are critical for laboratory operations, such as performance of protocol-mandated safety assays, peripheral blood mononuclear cell processing and immunological or endpoint assays from biological interventions on IND-registered clinical trials. The expectation is that compliance with the GCLP standards, monitored annually by external audits, will allow research and development laboratories to maintain data integrity and to provide immunogenicity, safety, and product efficacy data that is repeatable, reliable, auditable and that can be easily reconstructed in a research setting. (c) 2007 Elsevier B.V. All rights reserved. C1 [Rodriguez-Chavez, I. R.; D'Souza, M. P.] Natl Inst Hlth, Div Aids, Bethesda, MD 20817 USA. [Ezzelle, J.; Stirewalt, M.; Hitchcock, R.; Walter, T.] PPD Inc, Wilmington, NC 28401 USA. [Darden, J. M.; Kunwar, N.] Henry M Jackson Fdn Adv Mil Med, Rockville, MD 20852 USA. RP D'Souza, MP (reprint author), Natl Inst Hlth, Div Aids, 6700b Rockledge Dr, Bethesda, MD 20817 USA. EM pdsouza@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 34 TC 46 Z9 50 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JAN 7 PY 2008 VL 46 IS 1 BP 18 EP 29 DI 10.1016/j.jpba.2007.10.010 PG 12 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 254DK UT WOS:000252566400003 PM 18037599 ER PT J AU Grais, RF Conlan, AJK Ferrari, MJ Djibo, A Le Menach, A Bjornstad, ON Grenfell, BT AF Grais, R. F. Conlan, A. J. K. Ferrari, M. J. Djibo, A. Le Menach, A. Bjornstad, O. N. Grenfell, B. T. TI Time is of the essence: exploring a measles outbreak response vaccination in Niamey, Niger SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE epidemiology; vaccination; measles ID DEVELOPING-COUNTRIES; TRANSMISSION RATES; MASS VACCINATION; IMPACT; EPIDEMICS; STRATEGIES; INFECTION; MORTALITY; DYNAMICS; FORCE AB The current World Health Organization recommendations for response during measles epidemics focus on case management rather than outbreak response vaccination (ORV) campaigns, which may occur too late to impact morbidity and mortality and have a high cost per case prevented. Here, we explore the potential impact of an ORV campaign conducted during the 2003 2004 measles epidemic in Niamey, Niger. We measured the impact of this intervention and also the potential impact of alternative strategies. Using a unique geographical, epidemiologic and demographic dataset collected during the epidemic, we developed an individual-based simulation model. We estimate that a median of 7.6% [4.9 8.9] of cases were potentially averted as a result of the outbreak response, which vaccinated approximately 57% (84 563 of an estimated 148 600) of children in the target age range (6 59 months), 23 weeks after the epidemic started. We found that intervening early (up to 60 days after the start of the epidemic) and expanding the age range to all children aged 6 months to 15 years may lead to a much larger (up to 90%) reduction in the number of cases in a West African urban setting like Niamey. Our results suggest that intervening earlier even with lower target coverage (approx. 60%), but a wider age range, may be more effective than intervening later with high coverage (more than 90%) in similar settings. This has important implications for the implementation of reactive vaccination interventions as they can be highly effective if the response is fast with respect to the spread of the epidemic. C1 Epicentre, F-75011 Paris, France. Univ Cambridge, DAMTP, CMS, Cambridge CB3 0WA, England. Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. Minist Hlth, Niamey, Niger. Univ Paris 06, Inst Natl Sante Rech Med, Unit 707, F-75571 Paris, France. RP Grais, RF (reprint author), Epicentre, 8 Rue St Sabin, F-75011 Paris, France. EM rebecca.grais@epicentre.msf.org RI Bjornstad, Ottar/I-4518-2012 FU Wellcome Trust NR 33 TC 32 Z9 32 U1 1 U2 7 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD JAN 6 PY 2008 VL 5 IS 18 BP 67 EP 74 DI 10.1098/rsif.2007.1038 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 234EI UT WOS:000251143100006 PM 17504737 ER PT J AU Potash, JB Buervenich, S Cox, NJ Zandi, PP Akula, N Steele, J Rathe, JA Avramopoulos, D Detera-Wadleigh, SD Gershon, ES DePaulo, JR Feinberg, AP McMahon, FJ AF Potash, James B. Buervenich, Silvia Cox, Nancy J. Zandi, Peter P. Akula, Nirmala Steele, Jo Rathe, Jennifer A. Avramopoulos, Dimitrios Detera-Wadleigh, Sevilla D. Gershon, Elliot S. DePaulo, J. Raymond, Jr. Feinberg, Andrew P. McMahon, Francis J. CA NIMH Genetics Initiative Bipolar D TI Gene-Based SNP Mapping of a Psychotic Bipolar Affective Disorder Linkage Region on 22q12.3: Association With HMG2L1 and TOM1 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE bipolar disorder; psychotic; association; linkage disequilibrium; Writ signaling; HMG2L1 ID FAMILY-BASED ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISM; GENOME SCAN METAANALYSIS; CARDIO-FACIAL SYNDROME; SUSCEPTIBILITY LOCUS; SCHIZOPHRENIC-PATIENTS; DIAGNOSTIC INTERVIEW; CLINICAL-FEATURES; SYNTHASE KINASE-3; PEDIGREES AB Genetic linkage studies in both bipolar affective disorder (BPAD) and schizophrenia have implicated overlapping regions of chromosome 22q. We previously reported that BPAD pedigrees containing multiple members with psychotic symptoms showed suggestive linkage to chromosome 22q12.3. Now we have tested 189 single nucleotide polymorphisms (SNPs) spanning a 3 Mb region around the linkage peak for association with BPAD in 305 families, unrelated cases, and controls. SNPs were selected in or near genes, resulting in coverage at a density of 1 SNP per 6.7 kb across the 22 annotated genes in the region. The strongest signal emerged from family-based association analysis of an 11-SNP, 54 kb haplotype straddling the gene HMG2L1 and part of TOM1. A 3-marker haplotype of SNPs within TOM1 was associated with BPAD (allele-wise P = 0.0011) and with psychotic BPAD (allele-wise P = 0.00049). As hypothesized, the mean odds ratio for the risk alleles across the region was 1.39 in the psychotic but only 0.96 in the non-psychotic subset. Genotype-wise analyses yielded similar results, but the psychotic/non-psychotic distinction was more pronounced with mean odds ratios of 1.91 versus 0.8. Permutation of genotype-wise results for rs2413338 in HMG2L1 showed an empirical P = 0.037 for the difference between subsets. HMG2L1 is a negative regulator of Writ signaling, a pathway of interest in psychotic BPAD as it is activated by both mood stabilizer and anti-psychotic medications. Further work is needed to confirm these results and uncover the functional variation underlying the association signal. (C) 2007 Wiley-Liss, Inc. C1 [Potash, James B.; Rathe, Jennifer A.; Avramopoulos, Dimitrios; DePaulo, J. Raymond, Jr.] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. [Buervenich, Silvia; Akula, Nirmala; Steele, Jo; Detera-Wadleigh, Sevilla D.; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Bethesda, MD 20892 USA. [Cox, Nancy J.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Zandi, Peter P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Potash, JB (reprint author), Johns Hopkins Univ Hosp, Mood Disorders Program, 600 N Wolfe St,Meyer 4-119, Baltimore, MD 21287 USA. EM jpotash@jhmi.edu FU NIMH [R01 MH042243, U01 MH46282, U01 MH46280, U01 MH46274]; Stanley Medical Research Institute FX Grant sponsor: NIMH; Grant numbers: R01 MH042243, U01 MH46282, U01 MH46280, U01 MH46274; Grant sponsor: Stanley Medical Research Institute; Grant sponsor: NIMH Intramural Research Program. NR 63 TC 14 Z9 14 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN 5 PY 2008 VL 147B IS 1 BP 59 EP 67 DI 10.1002/ajmg.b.30574 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 246BB UT WOS:000251981400011 PM 17671966 ER PT J AU Goldenberg, RL Culhane, JF Iams, JD Romero, R AF Goldenberg, Robert L. Culhane, Jennifer F. Iams, Jay D. Romero, Roberto TI Preterm birth 1 - Epidemiology and causes of preterm birth SO LANCET LA English DT Review ID POLYMERASE-CHAIN-REACTION; FETAL INFLAMMATORY RESPONSE; AMNIOTIC-FLUID INFECTION; C-REACTIVE PROTEIN; BODY-MASS INDEX; INTRAAMNIOTIC INFECTION; UREAPLASMA-UREALYTICUM; INDICATED PRETERM; GESTATIONAL-AGE; DEPRESSIVE SYMPTOMS AB This paper is the first in a three-part series on preterm. birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or Caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries; however, the rate of preterm, birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm. births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm. labour and PPROM-together called spontaneous preterm births-are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth. C1 [Goldenberg, Robert L.; Culhane, Jennifer F.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19102 USA. [Iams, Jay D.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Goldenberg, RL (reprint author), Drexel Univ, Coll Med, Dept Obstet & Gynecol, 245 N 15th St,17th Floor,Room 17113, Philadelphia, PA 19102 USA. EM rgoldenb@drexelmed.edu NR 139 TC 2068 Z9 2180 U1 42 U2 296 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN 5 PY 2008 VL 371 IS 9606 BP 75 EP 84 DI 10.1016/S0140-6736(08)60074-4 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 248YH UT WOS:000252192600033 PM 18177778 ER PT J AU Larsen, BT Gutterman, DD Sato, A Toyama, K Campbell, WB Zeldin, DC Manthati, VL Falck, JR Miura, H AF Larsen, Brandon T. Gutterman, David D. Sato, Atsushi Toyama, Kazuyoshi Campbell, William B. Zeldin, Darryl C. Manthati, Vijay L. Falck, John R. Miura, Hiroto TI Hydrogen peroxide inhibits cytochrome P450 epoxygenases - Interaction between two endothelium-derived hyperpolarizing factors SO CIRCULATION RESEARCH LA English DT Article DE endothelium-derived hyperpolarizing factor; hydrogen peroxide; epoxyeicosatrienoic acid; cytochrome P450; reactive oxygen species ID EPOXIDE HYDROLASE INHIBITION; CA2+-ACTIVATED K+ CHANNELS; HUMAN MESENTERIC-ARTERIES; HUMAN CORONARY ARTERIOLES; INDUCED OXIDATIVE STRESS; EPOXYEICOSATRIENOIC ACIDS; SMOOTH-MUSCLE; DEPENDENT HYPERPOLARIZATION; CARDIOVASCULAR-DISEASES; MEDIATED RESPONSES AB The cytochrome P450 epoxygenase (CYP)-derived metabolites of arachidonic acid the epoxyeicosatrienoic acids (EETs) and hydrogen peroxide (H2O2) both function as endothelium-derived hyperpolarizing factors (EDHFs) in the human coronary microcirculation. However, the relative importance of and potential interactions between these 2 vasodilators remain unexplored. We identified a novel inhibitory interaction between CYPs and H2O2 in human coronary arterioles, where EDHF-mediated vasodilatory mechanisms are prominent. Bradykinin induced vascular superoxide and H2O2 production in an endothelium-dependent manner and elicited a concentration-dependent dilation that was reduced by catalase but not by 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE), 6-(2-propargyloxyphenyl) hexanoic acid, sulfaphenazole, or iberiotoxin. However, in the presence of catalase, an inhibitory effect of these compounds was unmasked. In a tandem-bioassay preparation, application of bradykinin to endothelium-intact donor vessels elicited dilation of downstream endothelium- denuded detectors that was partially inhibited by donor-applied catalase but not by detector-applied EEZE; however, EEZE significantly inhibited dilation in the presence of catalase. EET production by human recombinant CYP 2C9 and 2J2, 2 major epoxygenase isozymes expressed in human coronary arterioles, was directly inhibited in a concentration-dependent fashion by H2O2 in vitro, as observed by high-performance liquid chromatography (HPLC); however, EETs were not directly sensitive to oxidative modification. H2O2 inhibited dilation to arachidonic acid but not to 11,12-EET. These findings suggest that an inhibitory interaction exists between 2 EDHFs in the human coronary microcirculation. CYP epoxygenases are directly inhibited by H2O2, and this interaction may modulate vascular EET bioavailability. C1 [Gutterman, David D.; Sato, Atsushi; Toyama, Kazuyoshi; Miura, Hiroto] Med Coll Wisconsin, Ctr Cardiovasc, Dept Med, Milwaukee, WI 53226 USA. [Larsen, Brandon T.; Gutterman, David D.; Campbell, William B.] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. [Gutterman, David D.] Vet Adm Med Ctr, Milwaukee, WI 53295 USA. [Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Manthati, Vijay L.; Falck, John R.] SW Texas State Univ, Dept Biochem, Dallas, TX USA. RP Miura, H (reprint author), Med Coll Wisconsin, Ctr Cardiovasc, Dept Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM hmiura@mcw.edu OI Falck, John/0000-0002-9219-7845 FU Intramural NIH HHS [Z01 ES025034-13]; NHLBI NIH HHS [HL80173, HL51055, HL68769, P01 HL068769, R01 HL051055, R01 HL080173, R01 HL080173-01A2, R01 HL080173-02]; NIDDK NIH HHS [DK38266] NR 45 TC 68 Z9 68 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JAN 4 PY 2008 VL 102 IS 1 BP 59 EP 67 DI 10.1161/CIRCRESAHA.107.159129 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 249GX UT WOS:000252217400010 PM 17975109 ER PT J AU Thomas, JD Sloan, KB AF Thomas, Joshua D. Sloan, Kenneth B. TI In vitro evaluation of alkylcarbonyloxymethyl (ACOM) ethers as novel prodrugs of phenols for topical delivery: ACOM prodrugs of acetaminophen SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE prodrugs; diffusion cell experiments; topical delivery; Roberts-Sloan equation; transformed Potts-Guy equation; water solubility ID HAIRLESS MOUSE SKIN; 5-FLUOROURACIL 5-FU; TRANSDERMAL DELIVERY; PHYSICOCHEMICAL CHARACTERIZATION; SOLUBILITY PARAMETERS; STRATUM-CORNEUM; ESTER PRODRUGS; 6-MERCAPTOPURINE; DIFFUSION; THEOPHYLLINE AB The fluxes (J(IPM)) of a series of alkylcarbonyloxymethyl (ACOM) ethers of acetaminophen (APAP) were measured through hairless mouse skin from suspensions of each prodrug in isopropyl myristate (IPM). Solubilities in IPM, estimated solubilities in pH 4.0 buffer (S-4.0) and flux data for the 4-ACOM-APAP prodrugs were incorporated into the Roberts-Sloan (RS) database to give new estimates for the independent variables of the RS equation: log J(IPM) = x + y log S-IPM + (1 - y) log S-4.0 - zM(w). All but one of the 4-ACOM-APAP derivatives hydrolyzed completely on permeation through mouse skin. Three out of the five prodrugs permeated the skin better than APAP, with a maximum fourfold increase in flux. Biphasic solubility - not solubility in a single solvent - was shown to have the greatest impact on flux. A fit of the new n = 66 database to the RS equation gave the following values for x, y, z, and r(2): x = -0.545, y = 0.511, z = 0.00253, r(2) = 0.915. These results demonstrate that the topical delivery of a model phenol, acetaminophen, can be improved by transiently masking the phenolic hydroxyl group as an ACOM ether. (C) 2007 Elsevier B.V. All rights reserved. C1 [Sloan, Kenneth B.] Univ Florida, Dept Med Chem, Gainesville, FL 32610 USA. [Thomas, Joshua D.] NCI, NIH, Med Chem Lab, Ft Detrick, MD 21702 USA. RP Sloan, KB (reprint author), Univ Florida, Dept Med Chem, PO Box 100485, Gainesville, FL 32610 USA. EM sloan@cop.ufl.edu NR 42 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD JAN 4 PY 2008 VL 346 IS 1-2 BP 80 EP 88 DI 10.1016/j.ijpharm.2007.06.007 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 243PF UT WOS:000251809100009 PM 17629641 ER PT J AU Choi, H Leto, TL Hunyady, L Catt, KJ Bae, YS Rhee, SG AF Choi, Hyun Leto, Thomas L. Hunyady, Laszlo Catt, Kevin J. Bae, Yun Soo Rhee, Sue Goo TI Mechanism of angiotensin II-induced superoxide production in cells reconstituted with angiotensin type 1 receptor and the components of NADPH oxidase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE-CELLS; NUCLEOTIDE EXCHANGE FACTOR; ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAYS; INDUCED CARDIAC-HYPERTROPHY; PHOSPHOLIPASE-D ACTIVATION; COLON EPITHELIAL-CELLS; GROWTH-FACTOR RECEPTOR; SMALL GTPASE RAC; REACTIVE OXYGEN AB The mechanism of angiotensin II (Ang II)-induced superoxide production was investigated with HEK293 or Chinese hamster ovary cells reconstituted with the angiotensin type 1 receptor (AT(1)R) and NADPH oxidase (either Nox1 or Nox2) along with a pair of adaptor subunits (either NOXO1 with NOXA1 or p47(phox) with p67(phox)). Ang II enhanced the activity of both Nox1 and Nox2 supported by either adaptor pair, with more effective activation of Nox1 in the presence of NOXO1 and NOXA1 and of Nox2 in the presence of p47(phox) and p67(phox). Expression of several AT(1)R mutants showed that interaction of the receptor with G proteins but not that with beta-arrestin or with other proteins (Jak2, phospholipase C-gamma 1, SH2 domain-containing phosphatase 2) that bind to the COOH-terminal region of AT(1)R, was necessary for Ang II-induced superoxide production. The effects of constitutively active alpha subunits of G proteins and of various pharmacological agents implicated signaling by a pathway comprising AT1R, G alpha(q/11), phospholipase C-beta, and protein kinase C as largely, but not exclusively, responsible for Ang II-induced activation of Nox1 and Nox2 in the reconstituted cells. A contribution of G alpha(12/13), phospholipase D, and phosphatidylinositol 3-kinase to Ang II-induced superoxide generation was also suggested, whereas Src and the epidermal growth factor receptor did not appear to participate in this effect of Ang II. In reconstituted cells stimulated with Ang II, Nox2 exhibited a more sensitive response than Nox1 to the perturbation of protein kinase C, phosphatidylinositol 3-kinase, or the small GTPase Rac1. C1 [Choi, Hyun; Bae, Yun Soo; Rhee, Sue Goo] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea. [Leto, Thomas L.] NIH, NIAID, Host Def Lab, Bethesda, MD 20892 USA. [Hunyady, Laszlo] Semmelweis Univ, Dept Physiol, H-1088 Budapest, Hungary. [Catt, Kevin J.] NIH, NICHD, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Bae, YS (reprint author), Ewha Womans Univ, Div Life & Pharmaceut Sci, 1-1-1 Daehyundong,Seodamoongu, Seoul 120750, South Korea. EM baeys@ewha.ac.kr; rheesg@ewha.ac.kr NR 93 TC 33 Z9 34 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 4 PY 2008 VL 283 IS 1 BP 255 EP 267 DI 10.1074/jbc.M708000200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 245MV UT WOS:000251940300029 PM 17981802 ER PT J AU Liu, S Wang, H Currie, BM Molinolo, A Leung, HJ Moayeri, M Basile, JR Alfano, RW Gutkind, JS Frankel, AE Bugge, TH Leppla, SH AF Liu, Shihui Wang, Hailun Currie, Brooke M. Molinolo, Alfredo Leung, Howard J. Moayeri, Mahtab Basile, John R. Alfano, Randall W. Gutkind, J. Silvio Frankel, Arthur E. Bugge, Thomas H. Leppla, Stephen H. TI Matrix metalloproteinase-activated anthrax lethal toxin demonstrates high potency in targeting tumor vasculature SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATING TOXINS; PROTEIN-KINASE KINASE; PROTECTIVE ANTIGEN; MELANOMA-CELLS; CANCER; ANGIOGENESIS; MICE; SUSCEPTIBILITY; INACTIVATION; MACROPHAGES AB Anthrax lethal toxin ( LT), a virulence factor secreted by Bacillus anthracis, is selectively toxic to human melanomas with the BRAF V600E activating mutation because of its proteolytic activities toward the mitogen-activated protein kinase kinases (MEKs). To develop LT variants with lower in vivo toxicity and high tumor specificity, and therefore greater potential for clinical use, we generated a mutated LT that requires activation by matrix metalloproteinases (MMPs). This engineered toxin was less toxic than wild-type LT to mice because of the limited expression of MMPs by normal cells. Moreover, the systemically administered toxin produced greater anti-tumor effects than wild-type LT toward human xenografted tumors. This was shown to result from its greater bioavailability, a consequence of the limited uptake and clearance of the modified toxin by normal cells. Furthermore, the MMP-activated LT had very potent anti-tumor activity not only to human melanomas containing the BRAF mutation but also to other tumor types, including lung and colon carcinomas regardless of their BRAF status. Tumor histology and in vivo angiogenesis assays showed that this antitumor activity is due largely to the indirect targeting of tumor vasculature and angiogenic processes. Thus, even tumors genetically deficient in anthrax toxin receptors were still susceptible to the toxin therapy in vivo. Moreover, the modified toxin also displayed lower immunogenicity compared with the wild-type toxin. All these properties suggest that this MMP-activated antitumor toxin has potential for use in cancer therapy. C1 [Currie, Brooke M.; Molinolo, Alfredo; Basile, John R.; Gutkind, J. Silvio; Bugge, Thomas H.] NIH, NIDCR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. [Liu, Shihui; Wang, Hailun; Leung, Howard J.; Moayeri, Mahtab; Leppla, Stephen H.] NIH, NIAID, Lab Bacterial Dis, Bethesda, MD 20892 USA. [Alfano, Randall W.; Frankel, Arthur E.] Scott & White Mem Hosp & Clin, Canc Res Inst, Temple, TX 76502 USA. RP Bugge, TH (reprint author), NIH, NIDCR, Oral & Pharyngeal Canc Branch, Bldg 10, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov; sleppla@niaid.nih.gov RI Gutkind, J. Silvio/A-1053-2009 FU Intramural NIH HHS [Z01 AI000929-05] NR 40 TC 53 Z9 56 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 4 PY 2008 VL 283 IS 1 BP 529 EP 540 DI 10.1074/jbc.M707419200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 245MV UT WOS:000251940300058 PM 17974567 ER PT J AU Gagarina, V Carlberg, AL Pereira-Mouries, L Hall, DJ AF Gagarina, Viktoria Carlberg, Alyssa L. Pereira-Mouries, Lucilia Hall, David J. TI Cartilage oligomeric matrix protein protects cells against death by elevating members of the IAP family of survival proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIPLE EPIPHYSEAL DYSPLASIA; 5-STRANDED COILED-COIL; SMOOTH-MUSCLE-CELLS; NF-KAPPA-B; SYNOVIAL-FLUID; IX COLLAGEN; COMP; APOPTOSIS; PSEUDOACHONDROPLASIA; ACTIVATION AB Cartilage oligomeric matrix protein (COMP) is a component of cartilage, synovium, ligament, and tendon, yet its normal function is largely unknown. To identify its function we have expressed it in 293 and HeLa cell lines and in primary human chondrocytes. We find that COMP protects these cells against death, either in the presence or absence of tumor necrosis factor alpha and is able to block activation of caspase 3, a critical effector caspase. This effect appears to be mediated by the IAP (inhibitor of apoptosis protein) family of anti-apoptotic proteins because the levels of XIAP, survivin, cIAP1 and cIAP2 are significantly elevated in the COMP-expressing cells and down-regulation of survivin and XIAP protein levels by small interfering RNAs blocks the ability of COMP to enhance survival. The mRNAs for most of the IAP family members were not increased by COMP, indicating that a translational/post-translational mechanism was involved in their induction. However, in both HeLa cells and chondrocytes, COMP induced survivin mRNA by 5-fold. Thus survivin is the first gene identified to be up-regulated transcriptionally by COMP. The carboxyl-terminal half of the protein comprising the type 3 repeats and the RGD sequence (CaCTD domain) was sufficient to promote survival and to elevate the IAPs. Further, an RGD peptide was able to block the prosurvival effect of COMP and the induction of XIAP and survivin, indicating that survival is likely mediated through integrin signaling. These data point to a new role for COMP in protecting cells against death. C1 NIH, NIAMS, Cartilage Mol Genet Grp, Cartilage Biol & Orthoped Branch, Bethesda, MD 20892 USA. RP Hall, DJ (reprint author), NIH, NIAMS, Cartilage Mol Genet Grp, Cartilage Biol & Orthoped Branch, Bldg 13 Rm 3W17,9000 Rockville Pike, Bethesda, MD 20892 USA. EM halld@mail.nih.gov FU Intramural NIH HHS NR 53 TC 25 Z9 30 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 4 PY 2008 VL 283 IS 1 BP 648 EP 659 DI 10.1074/jbc.M704035200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 245MV UT WOS:000251940300069 PM 17993464 ER PT J AU Hartley, JW Evans, LH Green, KY Naghashfar, Z Macias, AR Zerfas, PM Ward, JM AF Hartley, Janet W. Evans, Leonard H. Green, Kim Y. Naghashfar, Zohreh Macias, Alfonso R. Zerfas, Patricia M. Ward, Jerrold M. TI Expression of infectious murine leukemia viruses by RAW264.7 cells, a potential complication for studies with a widely used mouse macrophage cell line SO RETROVIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; MICE; RETROVIRUSES; ASSAY; LEUKEMOGENESIS; REPLICATION; INDUCTION; COMPLEX; SYSTEM; GENE AB The mouse macrophage-like cell line RAW264.7, the most commonly used mouse macrophage cell line in medical research, was originally reported to be free of replication-competent murine leukemia virus (MuLV) despite its origin in a tumor induced by Abelson MuLV containing Moloney MuLV as helper virus. As currently available, however, we find that it produces significant levels of ecotropic MuLV with the biologic features of the Moloney isolate and also MuLV of the polytropic or MCF class. Newborn mice developed lymphoma following inoculation with the MuLV mixture expressed by these cells. These findings should be considered in interpretation of increasingly widespread use of these cells for propagation of other viruses, studies of biological responses to virus infection and use in RNA interference and cell signalling studies. C1 [Hartley, Janet W.; Naghashfar, Zohreh; Macias, Alfonso R.] NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. [Evans, Leonard H.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Green, Kim Y.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Zerfas, Patricia M.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. [Ward, Jerrold M.] NIH, NIAID, Comparat Med Branch, Bethesda, MD 20892 USA. RP Ward, JM (reprint author), NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. EM jhartley@niaid.nih.gov; levans@niaid.nih.gov; kgreen@niaid.nih.gov; znaghash@niaid.nih.gov; am327e@nih.gov; zerfasp@ors.od.nih.gov; jw116y@nih.gov FU Intramural NIH HHS NR 30 TC 31 Z9 31 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 4 PY 2008 VL 5 AR 1 DI 10.1186/1742-4690-5-1 PG 6 WC Virology SC Virology GA 265HL UT WOS:000253349600001 PM 18177500 ER PT J AU Mccutchan, TF AF Mccutchan, Thomas F. TI Beyond bed nets SO SCIENCE LA English DT Letter C1 NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Mccutchan, TF (reprint author), NIH, Lab Malaria & Vector Res, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 4 PY 2008 VL 319 IS 5859 BP 33 EP 33 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 247MM UT WOS:000252084000010 PM 18174419 ER PT J AU Kohjitani, A Fuda, H Hanyu, O Strott, CA AF Kohjitani, Atsushi Fuda, Hirotoshi Hanyu, Osamu Strott, Charles A. TI Regulation of SULT2B1a (pregnenolone sulfotransferase) expression in rat C6 glioma cells: Relevance of AMPA receptor-mediated NO signaling SO NEUROSCIENCE LETTERS LA English DT Article DE steroid sulfotransferase; neurosteroids; pregnenolone sulfate; learning and memory; AMPA receptor; nitric oxide; glial cell ID HUMAN HYDROXYSTEROID SULFOTRANSFERASE; NITRIC-OXIDE; HIPPOCAMPAL-NEURONS; SULFATE; NEUROSTEROIDS; MEMORY; BRAIN; GENE; RESPONSES; ISOFORMS AB The neurosteroid pregnenolone sulfate (PREGS), which is synthesized in glial cells, plays a significant role in learning and memory performance. The aim of this study was to investigate the regulation of expression of the steroid sulfotransferase SULT2B1a, which catalyzes the conversion of pregnenolone to PREGS, using the rat C6 glioma cell line. Rat C6 glioma cells expressed the SULT2B1a isoform, which sulfonates pregnenolone, but, neither the SULT2131b isoform, which catalyzes cholesterol, nor the prototypical steroid sulfotransferase SULT2A1 were expressed in these cells. Increasing concentrations of L-glutamic acid in the presence of cyclothiazide, which prevents AMPA receptor desensitization, attenuated SULT2B1a mRNA expression; however, neither NMDA nor kainic acid had a significant effect. Exposure to the synthetic glutamate analogue alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the presence of cyclothiazide also inhibited SULT2B1a expression. Attenuation of SULT2B1a expression by L-glutamic acid was reversed by the selective AMPA/kainate receptor antagonist 2,3-dioxo-6-vitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), and partially reversed by the specific neuronal nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI). Induction of inducible NOS by TNF-alpha in combination with lipopolysaccharide (LPS) dramatically attenuated SULT2B1a expression; this was partially reversed by the specific inducible NOS inhibitor N-6-(1-iminoethyl)-L-lysine hydrochloride (L-NIL). Furthermore, exposure to exogenous NO donors inhibited SULT2B1a mRNA expression, and exposure to sodium nitroprusside, LPS/TNF-alpha and L-glutamic acid in combination with cyclothiazide increased the production of nitrite, a stable degradation product of NO. These findings suggest that expression of SULT2B1a, which catalyzes PREGS production, is inhibited by activation of excitatory amino acid receptors of the AMPA subtype, via facilitation of intracellular NO signaling. Published by Elsevier Ireland Ltd. C1 [Kohjitani, Atsushi] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Dent Anesthesiol Field Oral & Maxillofacial, Kagoshima 890, Japan. [Kohjitani, Atsushi; Fuda, Hirotoshi; Hanyu, Osamu; Strott, Charles A.] NICHHD, NIH, Endocrinol & Reprod Res Branch, Sect Steroid Regulat, Bethesda, MD 20892 USA. RP Kohjitani, A (reprint author), Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Dent Anesthesiol Field Oral & Maxillofacial, Kagoshima 890, Japan. EM atsushik@denta.hal.kagoshima-u.ac.jp NR 27 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 3 PY 2008 VL 430 IS 1 BP 75 EP 80 DI 10.1016/j.neulet.2007.10.023 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 261IF UT WOS:000253071600015 PM 18054434 ER PT J AU Toyooka, N Zhou, D Kobayashi, S Tsuneki, H Wada, T Sakai, H Nemoto, H Sasaoka, T Tezuka, Y Subehan Kadota, S Garraffo, HM Spande, TF Daly, JW AF Toyooka, Naoki Zhou, Dejun Kobayashi, Soushi Tsuneki, Hiroshi Wada, Tsutomu Sakai, Hideki Nemoto, Hideo Sasaoka, Toshiyasu Tezuka, Yasuhiro Subehan Kadota, Shigetoshi Garraffo, H. Martin Spande, Thomas F. Daly, John W. TI Syntheses of the proposed structures of poison-frog alkaloids 179 and 207E and their inhibitory effects on neuronal nicotinic acetylcholine receptors SO SYNLETT LA English DT Article DE poison-frog alkaloids 179 and 207E; inhibitory effects on neuronal nicotinic acetylcholine receptors; dehydro-5,8-disubstituted indolizidines ID INDOLIZIDINE AB Syntheses of the structures postulated for 179 and 207E, members of a proposed new class of poison-frog alkaloids, 6,7-dehydro-5,8-disubstituted indolizidines, are described. The FT-IR spectrum and GC retention time of the synthetic 207E were different from those of the natural product; consequently the original structure of 207E needs to be revised. It is likely that the position of the double bond is instead at the 7,8-position. C1 [Toyooka, Naoki; Zhou, Dejun; Kobayashi, Soushi; Tsuneki, Hiroshi; Wada, Tsutomu; Sakai, Hideki; Nemoto, Hideo; Sasaoka, Toshiyasu] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Toyama 9300194, Japan. [Tezuka, Yasuhiro; Subehan; Kadota, Shigetoshi] Toyama Univ, Inst Natl Med, Toyama 9300194, Japan. [Garraffo, H. Martin; Spande, Thomas F.; Daly, John W.] NIDDK, NIH, Bioorgan Chem Lab, DHHS, Bethesda, MD 20892 USA. RP Toyooka, N (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. EM toyooka@pha.u-toyama.ac.jp OI Lallo, Subehan/0000-0003-1746-1682 NR 17 TC 4 Z9 4 U1 1 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0936-5214 J9 SYNLETT JI Synlett PD JAN 3 PY 2008 IS 1 BP 61 EP 64 DI 10.1055/s-2007-1000831 PG 4 WC Chemistry, Organic SC Chemistry GA 257BA UT WOS:000252773000011 ER PT J AU Imamichi, T Yang, J Huang, DW Brann, TW Fullmer, BA Adelsberger, JW Lempicki, RA Baseler, MW Lane, HC AF Imamichi, Tornozurni Yang, Jun Huang, Da-Wei Brann, Terrence W. Fullmer, Brandie A. Adelsberger, Joseph W. Lempicki, Richard A. Baseler, Michael W. Lane, H. Clifford TI IL-27, a novel anti-HIV cytokine, activates multiple interferon-inducible genes in macrophages SO AIDS LA English DT Article DE CD4 T cells; cytokines; gene regulation; interferon; interferon-inducible genes; macrophages ID CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; TH1 DIFFERENTIATION; ALPHA-INTERFERON; ANTIVIRAL ACTIONS; MOLECULAR CLONE; IN-VITRO; NAIVE; INFECTION; REPLICATION AB Objective: IL-27 is a novel anti-HIV cytokine that inhibits HIV-1 replication in both CD4 T cells and monocyte-derived macrophages (MDM) as IFN-alpha does. To elucidate the mechanism of the antiviral activity, we compared the activity and the gene expression profile of IL-27-treated cells with that of IFN-alpha-treated cells. Methods: CD4 T cells and monocytes were isolated from peripheral blood mononuclear cells of healthy donors. CD4 T cells were stimulated with phytohemagglutinin, and MDM were induced from monocytes using macrophage-colony stimulating factor. HIV-1 replication was monitored by p24 antigen capture assay. The gene expression profiles were analysed using DNA microarray analysis. The increase in the expression of IFN-inclucible genes (IFIG) was confirmed by the Quantigene plex assay. Results: Both cytokines preferentially inhibited HIV-1 replication in MDM compared with CD4 T cells. Quantitative real time polymerase chain reaction, enzyme-linked immunosorbent assay and neutralization assay using anti-IFN indicated that IFN-alpha, IFN-beta and IFN-gamma had no significant impact on IL-27-mediated HIV inhibition. DNA microarray analysis illustrated that IFN-alpha induced 33 and 18 IFIG in MDM and CD4 T cells, respectively. IL-27 induced 28 IFIG in MDM and five IFIG in CD4 T cells. The quantitative assay confirmed that IL-27 activated genes of RNA-dependent kinase, oligoadenylate synthetase, myxovirus protein, and apolipoprotein B messenger RNA-editing enzyme-catalytic polypepticle-like 3G. Conclusion: IL-27 differentially regulates the gene expression between CD4 T cells and MDM. IL-27 significantly induces antiviral genes in MDM as does IFN-alpha, suggesting that IL-27 inhibits HIV replication in MDM via mechanism(s) similar to that of IFN-alpha. (c) 2008 Wolters Kluwer Health. C1 [Imamichi, Tornozurni; Brann, Terrence W.] Natl Canc Inst, Lab Human Retrovirol, Frederick, MD USA. [Yang, Jun; Huang, Da-Wei; Fullmer, Brandie A.; Lempicki, Richard A.] Natl Canc Inst, Lab Immunopathogen & Bioinformat, Frederick, MD USA. [Adelsberger, Joseph W.] Natl Canc Inst, AIDS Monitoring Lab, Frederick, MD USA. [Yang, Jun; Huang, Da-Wei; Brann, Terrence W.; Fullmer, Brandie A.; Adelsberger, Joseph W.; Lempicki, Richard A.; Baseler, Michael W.] Natl Canc Inst, Sci Applicat Int Corp, Clin Serv Program, Appl & Dev Res Support Program, Frederick, MD USA. [Lane, H. Clifford] Natl Inst Hlth, NIAID, Immunoregulat Lab, Bethesda, MD USA. RP Imamichi, T (reprint author), NCI, SAIC Frederick Inc, Bldg 550, Rm 126, PO Box B, Ft Detrick, MD 21702 USA. EM timamichi@mail.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU NCI NIH HHS [N01-CO-12400] NR 44 TC 53 Z9 55 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2008 VL 22 IS 1 BP 39 EP 45 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 244DV UT WOS:000251847100005 PM 18090390 ER PT J AU Gardner, EA Sharma, S Peng, G Hullsiek, KH Burman, WJ MacArthur, RD Chesney, M Telzak, EE Friedland, G Mannheimer, SB AF Gardner, Edward A. Sharma, Shweta Peng, Grace Hullsiek, Katherine Huppler Burman, William J. MacArthur, Rodger D. Chesney, Margaret Telzak, Edward E. Friedland, Gerald Mannheimer, Sharon B. TI Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance SO AIDS LA English DT Article DE adherence; antiretroviral resistance; differential adherence; HIV; virological failure ID PROTEASE INHIBITORS; DRUG-RESISTANCE; VIRAL LOAD; PATTERNS; MEDICATION; TRIAL; POPULATION; PREDICTORS; MUTATIONS; INFECTION AB Objectives: To investigate the occurrence of differential adherence to components of combination antiretroviral therapy and assess its predictors and association with virological failure and antiretroviral medication resistance. Design: A secondary analysis of prospective clinical trial data. Methods: The Flexible Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus PI-based (three-class) antiretroviral therapy in treatment-naive HIV-1-infected individuals. Adherence was assessed at months 1 and 4, and then every 4 months. Differential adherence, defined as any difference in self-reported level of adherence to individual antiretroviral medications at the same timepoint, was evaluated as a binary time-updated variable in multivariate Cox regression analyses of time to initial virological failure (HIV-RNA > 1000 copies/ml) and initial virological failure with genotypic antiretroviral resistance. Results: Differential adherence was reported at least once by 403 of 1379 participants (29%), over 60 months median follow-up. Differential adherence was more commonly reported by participants randomly assigned to the three-class strategy (35%) than the NNRTI (28%) or PI (25%) strategies (P=0.005), but was not associated with demographic or baseline disease-specific factors. Of those reporting differential adherence, 146 (36%) reported it before initial virological failure. These participants had an increased risk of initial virological failure and initial virological failure with antiretroviral resistance compared with participants without differential adherence before initial virological failure. Conclusion: Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance. (c) 2008 Wolters Kluwer Health. C1 [Gardner, Edward A.; Burman, William J.] Denver Publ Hlth, Denver, CO 80204 USA. [Sharma, Shweta; Peng, Grace; Hullsiek, Katherine Huppler] Univ Minnesota, Minneapolis, MN USA. [MacArthur, Rodger D.] Wayne State Univ, Detroit, MI USA. [Chesney, Margaret] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Telzak, Edward E.] Bronx Lebanon Hosp Ctr, Bronx, NY USA. [Friedland, Gerald] Yale Univ, Sch Med, New Haven, CT USA. [Mannheimer, Sharon B.] Columbia Univ, Harlem Hosp, Coll Phys & Surg, New York, NY USA. RP Gardner, EA (reprint author), Denver Publ Hlth, 605 Bannock St, Denver, CO 80204 USA. EM edward.gardner@dhha.org FU NIAID NIH HHS [1U01AI068641, 5U01AI042170, 5U01AI046362, K01 AI067063, K01 AI067063-03, U01 AI042170, U01 AI046362, U01 AI068641] NR 25 TC 70 Z9 70 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2008 VL 22 IS 1 BP 75 EP 82 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 244DV UT WOS:000251847100009 PM 18090394 ER PT J AU Zeng, Z Guan, L An, P Sun, S O'Brien, SJ Winkler, CA AF Zeng, Zheng Guan, Li An, Ping Sun, Shan O'Brien, Stephen J. Winkler, Cheryl A. CA HBV Study Consortium TI A population-based study to investigate host genetic factors associated with hepatitis B infection and pathogenesis in the Chinese population SO BMC INFECTIOUS DISEASES LA English DT Article ID HEPATOCELLULAR-CARCINOMA RISK; REPUBLIC-OF-CHINA; VIRUS INFECTION; FULMINANT-HEPATITIS; LIVER-DISEASE; CORE PROMOTER; AFLATOXIN EXPOSURE; UNITED-STATES; RECEPTOR GENE; FOLLOW-UP AB Background: Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5 - 6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options. Methods/Design: This is a population-based, case-control study protocol to enroll 2200 Han Chinese from medical centers in northern and western China. Adult subjects in the following groups are being enrolled: healthy donors (n = 200), HBV infected persons achieving virus clearance (n = 400), asymptomatic HBV persistent carriers (n = 400), chronic hepatitis B cases (n = 400), decompensated liver cirrhosis with HBV infection cases (n = 400), and hepatocellular carcinoma with HBV infection cases (n = 400). In addition, for haplotype inference and quality control of sample handling and genotyping results, children of 1000 cases will be asked to provide a buccal sample for DNA extraction. With the exception of adult patients presenting with liver cirrhosis or HCC, all other cases and controls will be 40 years or older at enrollment. A questionnaire is being administered to capture dietary and environmental risk factors. Both candidate-gene and genome-wide association approaches will be used to assess the role of single genetic factors and higher order interactions with other genetic or environmental factors in HBV diseases. Conclusion: This study is designed and powered to detect single gene effects as well as gene-gene and environmental-gene interactions. The identification of allelic polymorphisms in genes involved in the pathway leading to chronic viral infection, liver cirrhosis and, ultimately, hepatocellular carcinoma would provide insights to those factors leading to HBV replication, liver inflammation, fibrosis, and the carcinogenic process. An understanding of the contribution of host genetic factors and their interactions may inform public health policy, improve diagnostics and clinical management, and provide targets for drug development. C1 [Guan, Li; An, Ping; O'Brien, Stephen J.; Winkler, Cheryl A.] Natl Canc Inst, SAIC, Lab Genom Divers, NIH, Frederick, MD USA. [Zeng, Zheng] Peking Univ, Hosp 1, Dept Infect Dis, Beijing 100871, Peoples R China. [Sun, Shan] Conservat Int China Program, Beijing, Peoples R China. RP Winkler, CA (reprint author), Natl Canc Inst, SAIC, Lab Genom Divers, NIH, Frederick, MD USA. EM zeng@bjmu.edu.cn; guanl@ncifcrf.gov; anp@ncifcrf.gov; shansun@conservation.org.cn; obrien@ncifcrf.gov; winkler@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400]; PHS HHS [IRB 02-C-N323] NR 56 TC 18 Z9 23 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JAN 2 PY 2008 VL 8 AR 1 DI 10.1186/1471-2334-8-1 PG 9 WC Infectious Diseases SC Infectious Diseases GA 262IO UT WOS:000253142400001 PM 18171470 ER PT J AU Wu, J Basha, MR Brock, B Cox, DP Cardozo-Pelaez, F McPherson, CA Harry, J Rice, DC Maloney, B Chen, D Lahiri, DK Zawia, NH AF Wu, Jinfang Basha, Md. Riyaz Brock, Brian Cox, David P. Cardozo-Pelaez, Fernando McPherson, Christopher A. Harry, Jean Rice, Deborah C. Maloney, Bryan Chen, Demao Lahiri, Debomoy K. Zawia, Nasser H. TI Alzheimer's disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (pb): Evidence for a developmental origin and environmental link for AD SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amyloidogenesis; development; environmental exposure; Pb; epigenetic regulation; transcription factor ID AMYLOID PRECURSOR PROTEIN; AGING BRAIN; OXIDATIVE DAMAGE; DNA METHYLATION; BETA-SECRETASE; ANIMAL-MODELS; HEART-DISEASE; PROMOTER; GENE; APP AB The sporadic nature of Alzheimer's disease (AD) argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead (Pb) during brain development predetermined the expression and regulation of the amyloid precursor protein (APP) and its amyloidogenic beta-amyloid (A beta) product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 (beta- site APP cleaving enzyme 1)] as well as their transcriptional regulator (Sp1) were elevated in aged (23-year-old) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of A beta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. C1 [Wu, Jinfang; Basha, Md. Riyaz; Brock, Brian; Zawia, Nasser H.] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA. [Cox, David P.; Cardozo-Pelaez, Fernando] Univ Montana, Dept Biomed & Pharmaceut Sci, Ctr Environm Hlth Sci, Missoula, MT 59812 USA. [McPherson, Christopher A.; Harry, Jean] Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Rice, Deborah C.] Maine Dept Hlth & Human Serv, Augusta, ME 04333 USA. [Maloney, Bryan; Chen, Demao; Lahiri, Debomoy K.] Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res,Lab Mol Neurogenet, Indianapolis, IN 46202 USA. RP Zawia, NH (reprint author), Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA. EM nzawia@uri.edu RI Maloney, Bryan/C-4924-2011 OI Maloney, Bryan/0000-0003-2364-9649 FU Intramural NIH HHS [Z01 ES021164-11]; NCRR NIH HHS [P20 RR015583, P20 RR016457, P20 RR017670, P20RR016457]; NIA NIH HHS [R01 AG018379, 1R15AG023604-01, AG027246, R01 AG018884, R03 AG027246, R0AG18379, R0AG18884]; NIEHS NIH HHS [ES013022, R21 ES013022] NR 48 TC 206 Z9 213 U1 0 U2 35 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 2 PY 2008 VL 28 IS 1 BP 3 EP 9 DI 10.1523/JNEUROSCI.4405-07.2008 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 249QC UT WOS:000252242900002 PM 18171917 ER PT J AU Du, J Creson, TK Wu, LJ Ren, M Gray, NA Falke, C Wei, YL Wang, Y Blumenthal, R Machado-Vieira, R Yuan, PX Chen, G Zhuo, M Manji, HK AF Du, Jing Creson, Thomas K. Wu, Long-Jun Ren, Ming Gray, Neil A. Falke, Cynthia Wei, Yanling Wang, Yun Blumenthal, Rayah Machado-Vieira, Rodrigo Yuan, Peixiong Chen, Guang Zhuo, Min Manji, Husseini K. TI The role of hippocampal GluR1 and GluR2 receptors in manic-like behavior SO JOURNAL OF NEUROSCIENCE LA English DT Article DE lithium; valproate; AMPA; PKA; phosphorylation; manic-like behavior ID AMPA RECEPTOR; BIPOLAR DISORDER; SYNAPTIC PLASTICITY; IN-VIVO; PHOSPHORYLATION SITES; SURFACE EXPRESSION; LITHIUM-CARBONATE; ANTIMANIC AGENTS; RAT HIPPOCAMPUS; PROTEIN-KINASE AB The cellular basis underlying the complex clinical symptomatology of bipolar disorder and the mechanisms underlying the actions of its effective treatments have not yet been fully elucidated. This study investigated the role of hippocampal synaptic AMPA receptors. We found that chronic administration of the antimanic agents lithium and valproate (VPA) reduced synaptic AMPA receptor GluR1/2 in hippocampal neurons in vitro and in vivo. Electrophysiological studies confirmed that the AMPA/NMDA ratio was reduced in CA1 regions of hippocampal slices from lithium-treated animals. Reduction in GluR1 phosphorylation at its cAMP-dependent protein kinase A site by the synthetic peptide TAT-S845, which mimics the effects of lithium or VPA, was sufficient to attenuate surface and synaptic GluR1/2 levels in hippocampal neurons in vitro and in vivo. Intrahippocampal infusion studies with the AMPA-specific inhibitor GYKI 52466 [4-(8-methyl-9H-1,3-dioxolo[4,5-h][ 2,3]benzodiazepin-5-yl)-benzenamine hydrochloride], a GluR1-specific TAT-S845 peptide, showed that GluR1/2 was essential for the development of manic/hedonic-like behaviors such as amphetamine- induced hyperactivity. These studies provide novel insights into the role of hippocampal GluR1/2 receptors in mediating facets of the manic syndrome and offer avenues for the development of novel therapeutics for these disorders. C1 [Du, Jing; Creson, Thomas K.; Gray, Neil A.; Falke, Cynthia; Wei, Yanling; Wang, Yun; Blumenthal, Rayah; Machado-Vieira, Rodrigo; Yuan, Peixiong; Chen, Guang; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Wu, Long-Jun; Ren, Ming; Zhuo, Min] Univ Toronto, Fac Med, Dept Physiol, Toronto, ON M5S 1A8, Canada. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, 9000 Rockville Pike,Bldg 35,1C912, Bethesda, MD 20892 USA. EM manji@nih.gov RI Zhuo, Min/A-2072-2008; Wu, Long-Jun /E-2684-2012; Wang, Yu Tian/A-4729-2008; MACHADO-VIEIRA, RODRIGO/D-8293-2012; Chen, Guang/A-2570-2017; OI Zhuo, Min/0000-0001-9062-3241; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Wu, Long-Jun/0000-0001-8019-3380 FU Intramural NIH HHS [Z01 MH002831-05] NR 64 TC 64 Z9 64 U1 2 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 2 PY 2008 VL 28 IS 1 BP 68 EP 79 DI 10.1523/JNEUROSCI.3080-07.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 249QC UT WOS:000252242900009 PM 18171924 ER PT J AU Paik, S Taniyama, Y Geyer, CE AF Paik, Soonmyung Taniyama, Yusuke Geyer, Charles E., Jr. TI Anthracyclines in the treatment of HER2-negative breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TRIAL COMPARING DOXORUBICIN; HER-2/NEU OVEREXPRESSION; C-ERBB-2 EXPRESSION; ADJUVANT THERAPY; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; WOMEN; GENE; CHEMOSENSITIVITY; DOCETAXEL C1 [Paik, Soonmyung; Taniyama, Yusuke; Geyer, Charles E., Jr.] Allegheny Gen Hosp, Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA 15212 USA. [Geyer, Charles E., Jr.] Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA 15212 USA. RP Paik, S (reprint author), Allegheny Gen Hosp, Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, 4 Allegheny Ctr 5th Floor,E Commons Profess Bldg, Pittsburgh, PA 15212 USA. EM soon.paik@nsabp.org NR 22 TC 8 Z9 9 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 2 PY 2008 VL 100 IS 1 BP 2 EP 4 DI 10.1093/jnci/djm277 PG 3 WC Oncology SC Oncology GA 254QR UT WOS:000252603600001 PM 18159066 ER PT J AU Aziz, NM Bellizzi, K AF Aziz, Noreen M. Bellizzi, Keith TI Older survivors and cancer care SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID OF-LIFE CARE; PALLIATIVE CARE; OPPORTUNITIES C1 [Aziz, Noreen M.; Bellizzi, Keith] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. RP Aziz, NM (reprint author), NCI, Off Canc Survivorship, NIH, 6116 Execut Blvd,Ste 404, Bethesda, MD 20892 USA. EM na45f@nih.gov NR 16 TC 7 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 2 PY 2008 VL 100 IS 1 BP 4 EP 5 DI 10.1093/jnci/djm278 PG 2 WC Oncology SC Oncology GA 254QR UT WOS:000252603600002 PM 18159065 ER PT J AU Aoyagi, S Archer, TK AF Aoyagi, Sayura Archer, Trevor K. TI Dynamics of coactivator recruitment and chromatin modifications during nuclear receptor mediated transcription SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE nuclear receptor; transcription; chromatin; coactivator; nucleosome ID IN-VIVO; POSTTRANSLATIONAL MODIFICATIONS; DEPENDENT TRANSCRIPTION; GLUCOCORTICOID-RECEPTOR; ANDROGEN RECEPTOR; STEROID-RECEPTORS; BINDING-SITES; COMPLEX; ACTIVATION; PROMOTER AB The mechanisms and interplay of coactivators that underlie transcription activation is a critical avenue of investigation in biology today. Using nuclear receptor (NR) mediated transcription activation as a model, the nature of coactivator recruitment and chromatin modifications has been found to be highly dynamic. Progress in understanding the kinetics and regulation of coactivator recruitment, and subsequent effects on transcriptional readout, has greatly improved our understanding of nuclear receptor mediated transcription, the subject of discussion in this 'At the Cutting Edge' review. Published by Elsevier Ireland Ltd. C1 [Aoyagi, Sayura; Archer, Trevor K.] Natl Inst Environm Hlth Sci, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), Natl Inst Environm Hlth Sci, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, 111 Alexander Dr,POB 12233,MD D4-01, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999, Z01 ES071006-09] NR 47 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 2 PY 2008 VL 280 IS 1-2 BP 1 EP 5 DI 10.1016/j.mce.2007.08.016 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 249MI UT WOS:000252232200001 PM 17935877 ER PT J AU Chou, J Luo, Y Kuo, CC Powers, K Shen, H Harvey, BK Hoffer, BJ Wang, Y AF Chou, J. Luo, Y. Kuo, C. -C. Powers, K. Shen, H. Harvey, B. K. Hoffer, B. J. Wang, Y. TI Bone morphogenetic protein-7 reduces toxicity induced by high doses of methamphetamine in rodents SO NEUROSCIENCE LA English DT Article DE methamphetamine; bone morphogenetic protein-7; tyrosine hydroxylase; protection; degeneration; gene expression ID DOPAMINERGIC-NEURONS; EXPRESSION; APOPTOSIS; BRAIN; NEUROPROTECTION; NEUROTOXICITY; PROTECTS; PATHWAY; RATS AB Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. We have previously demonstrated that pretreatment with bone morphogenetic protein 7 (BMP7) reduced 6-hydroxydopamine-mediated neurodegeneration in a rodent model of Parkinson's disease. In this study, we examined the neuroprotective effects of BMP7 against MA-mediated toxicity in dopaminergic neurons. Primary dopaminergic neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated with MA. High doses of MA decreased tyrosine hydroxylase immunoreactivity (THir) while increasing terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling. These toxicities were significantly antagonized by BMP7. Interaction of BMP7 and MA in vivo was first examined in CD1 mice. High doses of MA (10 mg/kg x 4 s.c.) significantly reduced locomotor activity and THir in striatum. I.c.v. administration of BMP7 antagonized these changes. In BMP7 +/- mice, MA suppressed locomotor activity and reduced TH immunoreactivity in nigra reticulata to a greater degree than in wild type BMP7 +/+ mice, suggesting that deficiency in BMP7 expression increases vulnerability to MA insults. Since BMP7 +/- mice also carry a LacZ-expressing reporter allele at the BMP7 locus, the expression of BMP7 was indirectly measured through the enzymatic activity of beta-galactosidase (beta-gal) in BMP7 +/- mice. High doses of MA significantly suppressed P-gal activity in striatum, suggesting that MA may inhibit BMP7 expression at the terminals of the nigrostriatal pathway. A similar effect was also found in CD1 mice in that high doses of MA suppressed BMP7 mRNA expression in nigra. In conclusion, our data indicate that MA can cause lesioning in the nigrostriatal dopaminergic terminals and that BMP7 is protective against MA-mediated neurotoxicity in central dopaminergic neurons. Published by Elsevier Ltd on behalf of IBRO. C1 [Chou, J.; Luo, Y.; Kuo, C. -C.; Powers, K.; Shen, H.; Harvey, B. K.; Hoffer, B. J.; Wang, Y.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. RP Wang, Y (reprint author), Natl Inst Drug Abuse, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov RI luo, Yu (Agnes)/E-4446-2010 FU Intramural NIH HHS NR 17 TC 24 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN 2 PY 2008 VL 151 IS 1 BP 92 EP 103 DI 10.1016/j.neuroscience.2007.10.044 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 254SR UT WOS:000252608800009 PM 18082966 ER PT B AU Kim, HS AF Kim, Hyong Soon GP ETRI TI IPv6 Pilot project experience in Korea SO 10TH INTERNATIONAL CONFERENCE ON ADVANCED COMMUNICATION TECHNOLOGY, VOLS I-III: INNOVATIONS TOWARD FUTURE NETWORKS AND SERVICES LA English DT Proceedings Paper CT 10th International Conference on Advanced Communication Technology CY FEB 17-20, 2008 CL Phoenix Pk, SOUTH KOREA SP Minist Informat & Commun, IEEE Commun Soc, IEEE Reg 10, Korean Inst Commun Sci, IEEK Commun Soc, Open Stand & Internet Assoc, Korea Inst Informat Scientists & Engineers, Inst Informat Technol Advancement, Korea Res Fdn, Elect & Telecommun Res Inst, Natl Informat Soc Agcy, Global IT Res Inst, IEEE Daejeon Sect DE IPv6; pilot projects; commercial services AB National Information Society Agency (NIA) successfully finished the administration of IPv6 Pilot projects from 2004 to 2007. For this project, we set up IPv6 service providing network with IPv6 portal, 6KANet and 6NGIX. Each system had essential functionality, to hold IPv6 early adopters and provide IPv6 services, and connectivity to commercially available IPv6 service providers in the world. This paper includes brief summarizations of various pilot projects NIA performed during the time. C1 NIA, Bethesda, MD 20892 USA. RP Kim, HS (reprint author), NIA, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI PISCATAWAY PA 445 HOES LN, PISCATAWAY, NJ 08854 USA BN 978-89-5519-135-6 PY 2008 BP 205 EP 206 PG 2 WC Computer Science, Software Engineering; Computer Science, Theory & Methods; Telecommunications SC Computer Science; Telecommunications GA BHO98 UT WOS:000254974600039 ER PT B AU Yum, CY Kim, HS Kang, S Song, J AF Yum, Chang Yeol Kim, Hyong Soon Kang, Sunmoo Song, JooSeok GP ETRI TI IPv4-related route optimization for DSMIPv6 SO 10TH INTERNATIONAL CONFERENCE ON ADVANCED COMMUNICATION TECHNOLOGY, VOLS I-III: INNOVATIONS TOWARD FUTURE NETWORKS AND SERVICES LA English DT Proceedings Paper CT 10th International Conference on Advanced Communication Technology CY FEB 17-20, 2008 CL Phoenix Pk, SOUTH KOREA SP Minist Informat & Commun, IEEE Commun Soc, IEEE Reg 10, Korean Inst Commun Sci, IEEK Commun Soc, Open Stand & Internet Assoc, Korea Inst Informat Scientists & Engineers, Inst Informat Technol Advancement, Korea Res Fdn, Elect & Telecommun Res Inst, Natl Informat Soc Agcy, Global IT Res Inst, IEEE Daejeon Sect DE MIPv6; DSMtPv6; correspond node; route optimization AB DSMIPv6's specification allows the transport of both IPv4 and IPv6 packets over a tunnel to the RA and the Mobile Node to roam over both IPv6 and IPv4. This paper adds the methods to support route optimization for handover during moving to IPv4 network or using IPv4 application. C1 [Yum, Chang Yeol; Kim, Hyong Soon; Kang, Sunmoo] NIA, Bethesda, MD 20892 USA. RP Yum, CY (reprint author), NIA, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI PISCATAWAY PA 445 HOES LN, PISCATAWAY, NJ 08854 USA BN 978-89-5519-135-6 PY 2008 BP 1554 EP 1556 PG 3 WC Computer Science, Software Engineering; Computer Science, Theory & Methods; Telecommunications SC Computer Science; Telecommunications GA BHO98 UT WOS:000254974602015 ER PT S AU Chowdhury, AS Yao, J VanUitert, RL Linguraru, MG Summers, RM AF Chowdhury, A. S. Yao, J. VanUitert, R. L. Linguraru, M. G. Summers, R. M. GP IEEE TI Detection of Anatomical Landmarks in Human Colon from Computed Tomographic Colonography Images SO 19TH INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION, VOLS 1-6 SE International Conference on Pattern Recognition LA English DT Proceedings Paper CT 19th International Conference on Pattern Recognition (ICPR 2008) CY DEC 08-11, 2008 CL Tampa, FL SP IEEE DE Heat Diffusion; Fuzzy C-Means; Frenet Frame; Haustral Fold; Tenia Coli; Computed Tomography ID CT COLONOGRAPHY; POLYP DETECTION; DIFFUSION AB Colon cancer is the second leading cause of cancer-related deaths per year in industrial nations. Virtual colonoscopy is a new, less invasive alternative to the usually practiced optical colonoscopy for colorectal polyp and cancer screening. In this paper, we present some physics-based modeling and pattern recognition techniques to identify anatomical landmarks in the human colon like the haustral folds and the tenia coli to further exploit the benefits of virtual colonoscopy. A combination of heat diffusion field algorithm and fuzzy c-means clustering algorithm is used to defect the haustral folds in human colon from volumetric computed tomography (CT) images. Each voxel on the corresponding colon surface is parameterized using the colon centerline information and associated local Frenet frames. The parameterized fold information is utilized to establish the tentative location of one tenia coli. Preliminary results on automated detection of tenia coli are shown on the colon surface. C1 [Chowdhury, A. S.; Yao, J.; VanUitert, R. L.; Linguraru, M. G.; Summers, R. M.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Chowdhury, AS (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1C368X, Bethesda, MD 20892 USA. EM chowdhuryas@mail.nih.gov; rms@mail.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-4651 BN 978-1-4244-2174-9 J9 INT C PATT RECOG PY 2008 BP 88 EP 91 PG 4 WC Computer Science, Artificial Intelligence SC Computer Science GA BJC36 UT WOS:000264729000022 ER PT S AU Yao, JH Avila, N Dwyer, A Taveira-Dasilva, AM Hathaway, OM Moss, J AF Yao, Jianhua Avila, Nilo Dwyer, Andrew Taveira-Dasilva, Angelo M. Hathaway, Olanda M. Moss, Joel GP IEEE TI Computer-Aided Grading of Lymphangioleiomyomatosis (LAM) using HRCT SO 19TH INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION, VOLS 1-6 SE International Conference on Pattern Recognition LA English DT Proceedings Paper CT 19th International Conference on Pattern Recognition (ICPR 2008) CY DEC 08-11, 2008 CL Tampa, FL SP IEEE ID LUNG AB Lymphangioleiomyomatosis (LAM is a multisystem disorder associated with proliferation of smooth muscle-like cells, which leads to destruction of lung parenchyma. Subjective grading of LAM on HRCT is imprecise and can be arduous especially in cases with severe involvement. We propose a computer-aided evaluation system that grades LAM involvement based on analysis of lung texture patterns. A committee of support vector machines is employed for classification. The system was tested on 36 patients. The computer grade demonstrates good correlation with subjective radiologist grade (R=0.91, p<0.0001) and pulmonary functional tests (R=0.85, p<0.0001). The grade also provides precise progression assessment of disease over time. C1 [Yao, Jianhua; Avila, Nilo; Dwyer, Andrew] NHLBI, Dept Diagnost Radiol, Ctr Clin, NIH, Bldg 10, Bethesda, MD 20892 USA. [Taveira-Dasilva, Angelo M.; Hathaway, Olanda M.; Moss, Joel] NIH, NHLBI, Translat Med Branch, Bethesda, MD USA. RP Yao, JH (reprint author), NHLBI, Dept Diagnost Radiol, Ctr Clin, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-4651 BN 978-1-4244-2174-9 J9 INT C PATT RECOG PY 2008 BP 176 EP + PG 2 WC Computer Science, Artificial Intelligence SC Computer Science GA BJC36 UT WOS:000264729000044 ER PT S AU Wang, SJ Yao, JH Summers, RM AF Wang, Shijun Yao, Jianhua Summers, Ronald M. GP IEEE TI Matching Colonic Polyps from Prone and Supine CT Colonography Scans Based on Statistical Curvature Information SO 19TH INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION, VOLS 1-6 SE International Conference on Pattern Recognition LA English DT Proceedings Paper CT 19th International Conference on Pattern Recognition (ICPR 2008) CY DEC 08-11, 2008 CL Tampa, FL SP IEEE ID POPULATION AB Computed tomographic colonography (CTC) provides a feasible way for the detection of colorectal polyps and cancer screening. In the clinical practice of CTC, a true colonic polyp will be confirmed with high confidence if a radiologist can find it in both the supine and prone scans. To assist radiologists in CTC reading, we propose a new colonic polyp matching method based on statistical curvature information of polyp candidates. We first extract histograms of curvature-related features (HCF) from each polyp candidate, then use diffusion map to embed the original high dimensional data into a low-dimensional space. Experimental results show that by using our HCF method, we can improve the sensitivity from 0.58 to 0.74 at false positive rate 0.1 compared with a traditional method that uses only means of curvature related features. C1 [Wang, Shijun; Yao, Jianhua; Summers, Ronald M.] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Wang, SJ (reprint author), NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM wangshi@cc.nih.gov; jyao@cc.nih.gov; rms@nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-4651 BN 978-1-4244-2174-9 J9 INT C PATT RECOG PY 2008 BP 180 EP 183 PG 4 WC Computer Science, Artificial Intelligence SC Computer Science GA BJC36 UT WOS:000264729000045 ER PT S AU Wang, SJ Zhang, CS AF Wang, Shijun Zhang, Changshui GP IEEE TI Collaborative Learning by Boosting in Distributed Environments SO 19TH INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION, VOLS 1-6 SE International Conference on Pattern Recognition LA English DT Proceedings Paper CT 19th International Conference on Pattern Recognition (ICPR 2008) CY DEC 08-11, 2008 CL Tampa, FL SP IEEE ID ALGORITHMS; CLASSIFICATION; PARALLEL AB In this paper we propose a new distributed learning method called distributed network boosting (DNB) algorithm for distributed applications. The learned hypotheses are exchanged between neighboring sites during learning process. Theoretical analysis shows that the DNB algorithm minimizes the cost function through the collaborative Junctional gradient descent in hypotheses space. Comparison results of the DNB algorithm with other distributed learning methods on real data sets with different sizes show its effectiveness. C1 [Wang, Shijun] Natl Inst Hlth, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Zhang, Changshui] Tsinghua Univ, Dept Automat, Beijing 100084, Peoples R China. RP Wang, SJ (reprint author), Natl Inst Hlth, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM sjwang05@gmail.com; zcs@mail.tsinghua.edu.cn FU National 863 [2006AA10Z210] FX Thiswork was supported by the National 863 project (No. 2006AA10Z210). NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-4651 BN 978-1-4244-2174-9 J9 INT C PATT RECOG PY 2008 BP 745 EP + PG 2 WC Computer Science, Artificial Intelligence SC Computer Science GA BJC36 UT WOS:000264729000183 ER PT S AU Xue, ZY Long, LR Antani, S Thoma, GR Jeronimo, J AF Xue, Zhiyun Long, L. Rodney Antani, Sameer Thoma, George R. Jeronimo, Jose GP IEEE TI Cervicographic Image Retrieval by Spatial Similarity of Lesions SO 19TH INTERNATIONAL CONFERENCE ON PATTERN RECOGNITION, VOLS 1-6 SE International Conference on Pattern Recognition LA English DT Proceedings Paper CT 19th International Conference on Pattern Recognition (ICPR 2008) CY DEC 08-11, 2008 CL Tampa, FL SP IEEE AB The National Library of Medicine has been developing CervigramFinder, a Web-accessible prototype content-based image retrieval (CBIR) system for cervical cancer research, to retrieve cervicographic images from a large collection with respect to visual characteristics of lesion regions. This paper describes current work on retrieving the images based on similarity of spatial location of lesions. The proposed two-level method takes into account the visual characteristics of cervix lesions, as well as spatial information of shape, size, orientation, and distance. The proposed method was evaluated on a data set of 1000 cervicographic images where multiple lesion boundaries as well as associated location information were marked by medical experts. The simplicity and effectiveness of the proposed method was subjectively compared with the Angle Histogram and R-Histogram and was evaluated as better with respect to results ranking. C1 [Xue, Zhiyun; Long, L. Rodney; Antani, Sameer; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Jeronimo, Jose] Reproduct Hlth, Program Appropriate Technol Hlthcare, Seattle, WA USA. RP Xue, ZY (reprint author), NIH, Natl Lib Med, Bethesda, MD 20892 USA. EM xuez@mail.nih.gov; rlong@mail.nih.gov; santani@mail.nih.gov; gthoma@mail.nih.gov; jjeronimo@path.org FU Intramural Research Program of the National Institutes of Health (NIH); National Library of Medicine (NLM); Lister Hill National Center for Biomedical Communications (LHNCBC) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine (NLM), and Lister Hill National Center for Biomedical Communications (LHNCBC). NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-4651 BN 978-1-4244-2174-9 J9 INT C PATT RECOG PY 2008 BP 2230 EP 2233 PG 4 WC Computer Science, Artificial Intelligence SC Computer Science GA BJC36 UT WOS:000264729001064 ER PT S AU Wu, DW Zhou, QF Zhu, BP Shung, KK Djuth, FT Liu, CG AF Wu, D. W. Zhou, Q. F. Zhu, B. P. Shung, K. K. Djuth, F. T. Liu, C. G. GP IEEE TI High-frequency (> 100MHz) PZT Thick Film Transducers and Kerfless Arrays SO 2008 17TH IEEE INTERNATIONAL SYMPOSIUM ON THE APPLICATIONS OF FERROELECTRICS SE IEEE International Symposium on Applications of Ferroelectrics LA English DT Proceedings Paper CT 17th IEEE International Symposium on Applications of Ferroelectrics CY FEB 23-28, 2008 CL Santa Fe, NM SP IEEE AB This paper presents the latest development of high-frequency (>100MHz) PZT film ultrasonic transducers and kerfless arrays. PZT thick films of 12 mu m in thickness were fabricated with a spin-coating method. The films were found to have a remanent polarization of 33 mu C/cm(2) and a coercive field Ec of 70 kV/cm. High-frequency (120MHz) single element transducers and a kerfless array were successfully fabricated with these films. The transducer and array have -6dB bandwidth of 40% without matching, and 60% with a layer of parylene as the matching layer. The single element transducer was found to have an axial resolution of 20 mu m and lateral resolution of 100 mu m. Ultrasonic images of a porcine eye were also successfully acquired with the single element transducer. Kerfless array imaging is onging. C1 [Wu, D. W.; Zhou, Q. F.; Zhu, B. P.; Shung, K. K.] Univ Southern Calif, Transducer Resource Ctr, NIH, Los Angeles, CA 90089 USA. [Djuth, F. T.; Liu, C. G.] Geospace Res Inc, El Segundo, CA 90245 USA. RP Wu, DW (reprint author), Univ Southern Calif, Transducer Resource Ctr, NIH, Los Angeles, CA 90089 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1099-4734 BN 978-1-4244-2744-4 J9 IEEE INT FERRO PY 2008 BP 527 EP + PG 2 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Physics, Applied SC Engineering; Materials Science; Physics GA BLN41 UT WOS:000270584000190 ER PT S AU Hernando, D Kellman, P Haldar, JP Liang, ZP AF Hernando, D. Kellman, P. Haldar, J. P. Liang, Z. -P. GP IEEE TI A Network Flow Method for Improved MR Field Map Estimation in the Presence of Water and Fat SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID GRAPH CUTS; DECOMPOSITION AB Field map estimation is an important problem in MRI, with applications such as water/fat separation and correction of fast acquisitions. However, it constitutes a nonlinear and severely ill-posed problem requiring regularization. In this paper, we introduce an improved method for regularized field map estimation, based on a statistically motivated formulation, as well as a novel algorithm for the solution of the corresponding optimization problem using a network flow approach. The proposed method provides theoretical guarantees (local optimality with respect to a large move), as well as an efficient implementation. It has been applied to the water/fat separation problem and tested on a number of challenging datasets, showing high-quality results. C1 [Hernando, D.; Haldar, J. P.; Liang, Z. -P.] Univ Illinois, Dept Elect & Comp Engn, 1406 W Green St, Urbana, IL 61801 USA. [Kellman, P.] NIH, Natl Heart Lung & Blood Inst, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hernando, D (reprint author), Univ Illinois, Dept Elect & Comp Engn, 1406 W Green St, Urbana, IL 61801 USA. EM dhernan2@uiuc.edu; kellmanp@nhlbi.nih.gov; haldar@uiuc.edu; z-liang@uiuc.edu RI Haldar, Justin/B-4983-2008 OI Haldar, Justin/0000-0002-1838-0211 FU [NIHP41- EB03631-16]; [NIH-R01-CA098717] FX This work was supported in part by the following research grants: NIHP41- EB03631-16 and NIH-R01-CA098717. NR 19 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 82 EP + DI 10.1109/IEMBS.2008.4649096 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404500023 ER PT S AU Reyes, M Ballester, MAG Li, ZX Kozic, N Summers, RM Linguraru, MG AF Reyes, Mauricio Ballester, Miguel A. Gonzalez Li, Zhixi Kozic, Nina Summers, Ronald M. Linguraru, Marius George GP IEEE TI Interpretability of Anatomical Variability Analysis of Abdominal Organs via Clusterization of Decomposition Modes SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID MR-IMAGES; SEGMENTATION AB Extensive recent work has taken place on the construction of probabilistic atlases of anatomical organs, especially the brain, and their application in medical image analysis. These techniques are leading the way into similar studies of other organs and more comprehensively of groups of organs. In this paper we report results on the analysis of anatomical variability obtained from probabilistic atlases of abdominal organs. Two factor analysis techniques, namely principal component analysis (PCA) and principal factor analysis (PFA), were used to decompose and study shape variability within the abdomen. To assess and case the Interpretability of the resulting deformation modes, a clustering technique of the deformation vectors is proposed. The analysis of deformation fields obtained using these two factor analysis techniques showed strong correlation with anatomical landmarks and known mechanical deformations in the abdomen, allowing us to conclude that PFA is a complementary decomposition technique that offers easy-to-interpret additional information to PCA in a clinical setting. The analysis of organ anatomical variability will represent a potentially important research tool for abdominal diagnosis and modeling. C1 [Reyes, Mauricio; Kozic, Nina] Univ Bern, MEM Res Ctr, Inst Surg Technol & Biomech, CH-3012 Bern, Switzerland. [Ballester, Miguel A. Gonzalez] Alma Syst, Barcelona, Spain. [Li, Zhixi; Summers, Ronald M.; Linguraru, Marius George] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Reyes, M (reprint author), Univ Bern, MEM Res Ctr, Inst Surg Technol & Biomech, CH-3012 Bern, Switzerland. EM mauricio.reyes@memcenter.unibe.ch; lingurarum@mail.nih.gov RI Gonzalez Ballester, Miguel Angel/D-1349-2013; OI Gonzalez Ballester, Miguel Angel/0000-0002-9227-6826; Gonzalez Ballester, Miguel Angel/0000-0002-1862-9590 FU National Institutes of Health; Clinical Center FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, Clinical Center. The authors would like to acknowledge Mr. See Chin for providing the manual segmentations of the organs used in this study. NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 355 EP + DI 10.1109/IEMBS.2008.4649163 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404500090 ER PT S AU Klee, MM AF Klee, Maurice M. GP IEEE TI Charge Distributions of Active Biological Pores SO 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vols 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn AB Charge distributions associated with active biological pores are calculated. The charge distributions include rings of reverse-sign, current-turning charges which surround the entrance and exit ends of the pore and cause current to turn into the pore at its entrance end (e.g., the intracellular side of a potassium pore) and to turn outward from the pore at its exit end (e.g., the extracellular side of a potassium pore). The magnitude and spatial extent of the rings depend directly on the magnitude of the current passing through the pore. In the absence of current, the rings disappear and when, for example, the pore's resistance becomes the dominant resistance in the system, the magnitude and spatial extent of the rings saturate. The reverse-sign, current-turning charges affect the local environment of proteins, such as ligand-binding proteins, known to reside adjacent to biological pores. The charges are thus expected to play a role in pore function such as by modulating the binding of charged species to the binding proteins. C1 NIDDK, Lab Biol Modeling, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Klee, MM (reprint author), NIDDK, Lab Biol Modeling, Natl Inst Hlth, Bethesda, MD 20892 USA. EM mk@mauricklee.com NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 563 EP 566 DI 10.1109/IEMBS.2008.4649215 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404500142 ER PT S AU Linguraru, MG Orandi, BJ Van Uitert, RL Mukherjee, N Summers, RM Gladwin, MT Machado, RF Wood, BJ AF Linguraru, Marius George Orandi, Babak J. Van Uitert, Robert L. Mukherjee, Nisha Summers, Ronald M. Gladwin, Mark T. Machado, Roberto F. Wood, Bradford J. GP IEEE TI CT and Image Processing Non-invasive Indicators of Sickle Cell Secondary Pulmonary Hypertension SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID RISK-FACTOR; DISEASE; DEATH AB This retrospective study investigates the potential of image analysis to quantify for the presence and extent of pulmonary hypertension secondary to sickle cell disease (SCD). A combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery from smoothed CT-Angiography images from 16 SCD patients and 16 matching controls. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries to measure automatically the diameters of the pulmonary trunk and first branches of the pulmonary arteries. Results show that the pulmonary trunk and arterial branches are significantly larger in diameter in SCD patients as compared to controls (p-values of 0.002 for trunk and 0.0003 for branches). For validation, the results were compared with manually measured values and did not demonstrate significant difference (mean p-values 0.71). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance. C1 [Linguraru, Marius George; Orandi, Babak J.; Summers, Ronald M.; Wood, Bradford J.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Van Uitert, Robert L.] CAD Inc, Nashua, NH 03062 USA. [Mukherjee, Nisha] Duke Univ, Sch Med, Durham, NC 27706 USA. [Gladwin, Mark T.; Machado, Roberto F.] Natl Inst Hlth, Ctr Clin, NHLBI, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Linguraru, MG (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. EM lingurarum@mail.nih.gov FU ational Institutes of Health; Clinical Center and National Heart, Lung, and Blood Institute; Clinical Research Training Program; NIH; Pfizer Inc FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, Clinical Center and National Heart, Lung, and Blood Institute. B.J. Orandi was funded by the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc. NR 18 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 859 EP + DI 10.1109/IEMBS.2008.4649289 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404500216 ER PT S AU Linguraru, MG Zhao, S Van Uitert, RL Liu, JM Fletcher, JG Manduca, A Summers, RM AF Linguraru, Marius George Zhao, Shan Van Uitert, Robert L. Liu, Jiamin Fletcher, Joel G. Manduca, Armando Summers, Ronald M. GP IEEE TI CAD of Colon Cancer on CT Colonography Cases without Cathartic Bowel Preparation SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID VIRTUAL COLONOSCOPY; PERFORMANCE AB Computer-aided diagnosis (CAD) systems must show sufficient versatility to produce robust analysis on a large variety of data. In the case of colonography, CAD has not been designed to cope with the presence of stool, although labeling the stool with high contrast agents replaces the use of laxatives and reduces the patient discomfort. This procedure introduces additional challenges for the diagnosis, such as poorly tagged stool, stool sticking to colonic walls, and heterogeneous stool (tagged stool mixed with air or untagged stool). Our study proposes a robust algorithm for heterogeneous stool removal to be employed as a preprocessing module for CAD systems in colonic cancer detection. Colonoscopy data are automatically cleansed of residual stool to enhance the polyp appearance for improved diagnosis. The algorithm uses expectation-maximization, quadratic regression, level sets and minimum variance. Results show stool removal accuracy on polyps which are partially or fully covered by stool. The results are robust on stool lining and large pools of heterogeneous and weakly-tagged stool. The automatic detection of colon polyps using our CAD system on cathartic-free data improves considerably with the addition of the automatic stool removal module from 74% to 86% true positive (TP) rate at 6.4 false positives (FP)/case. C1 [Linguraru, Marius George; Zhao, Shan; Liu, Jiamin; Summers, Ronald M.] NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Van Uitert, Robert L.] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Van Uitert, Robert L.] ICAD Inc, Nashua, NH 03062 USA. [Fletcher, Joel G.; Manduca, Armando] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. RP Linguraru, MG (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM lingurarum@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, Clinical Center FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, Clinical Center NR 11 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 2996 EP + DI 10.1109/IEMBS.2008.4649833 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404501353 ER PT S AU Varghese, RS Goldman, L An, YM Loffredo, CA Abdel-Hamid, M Kyselova, Z Mechref, Y Novotny, M Drake, SK Goldman, R Ressom, HW AF Varghese, Rency S. Goldman, Lenka An, Yanming Loffredo, Christopher A. Abdel-Hamid, Mohamed Kyselova, Zuzana Mechref, Yehia Novotny, Milos Drake, Steve K. Goldman, Radoslav Ressom, Habtom W. GP IEEE TI Integrated Peptide and Glycan Biomarker Discovery Using MALDI-TOF Mass Spectrometry SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID HEPATOCELLULAR-CARCINOMA; SERUM; HCV AB Quantitative comparison of peptides and glycans in serum is conducted using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to identify biomarkers. A peak selection algorithm is developed to identify a panel of integrated peptide and glycan peaks to distinguish hepatocellular carcinoma (HCC) cases from high-risk population of patients with chronic liver disease (CLD). Candidate peptide and glycan markers selected frequently in multiple runs of the algorithm are presented. The performance of these markers is evaluated in terms of their ability to distinguish HCC cases from patients with CLD in a blinded validation set. C1 [Varghese, Rency S.; Goldman, Lenka; An, Yanming; Loffredo, Christopher A.; Goldman, Radoslav; Ressom, Habtom W.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Drake, Steve K.] NIH, Dept Lab Med, Clin Chem Serv, Bethesda, MD USA. [Abdel-Hamid, Mohamed] NHTMRI, Viral Hepatitis Res Lab, Cairo, Egypt. [Kyselova, Zuzana; Mechref, Yehia; Novotny, Milos] Natl Ctr Glycom & Glycoproteom, Dept Chem, Bloomington, IN USA. RP Ressom, HW (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. EM hwr@georgetown.edu RI Varghese, Rency/A-8770-2012; OI Mechref, Yehia/0000-0002-6661-6073 FU National Cancer Institute (NCI) [R21 CA130837, NCI R03 CA119313]; NCI Early Detection Research Network Associate Membership Grant; Prevent Cancer Foundation Grant [R01 CA115625] FX This work was supported in part by the National Cancer Institute (NCI) R21 CA130837 Grant, NCI R03 CA119313 Grant, NCI Early Detection Research Network Associate Membership Grant, and the Prevent Cancer Foundation Grant awarded to HWR; R01 CA115625 Grant awarded to RG. R. S. Varghese, L. Goldman, Y. An, C. A. Loffredo, R. Goldman, and H. W. Ressom are with the Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, NR 11 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 3791 EP + DI 10.1109/IEMBS.2008.4650034 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404502143 ER PT S AU Allin, SJ Beach, C Mitz, A Mihailidis, A AF Allin, Sonya J. Beach, Cheryl Mitz, Andrew Mihailidis, Alex GP IEEE TI Video based analysis of standing balance in a community center SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID POSTURAL CONTROL; SWAY; POSTUROGRAPHY; MOVEMENTS; TRACKING; FALLS; AGE AB Postural sway is a well known measure of postural stability in the elderly. Sway measurements, however, are typically made using expensive equipment in a laboratory. We report on efforts to make clinically significant and quantitative measurements of postural sway in a community center with a single un-calibrated video camera. Results indicate that simple tracking technologies can capture some aspects of sway in a community center in a way that is perceptually accurate and capable of distinguishing expert-assigned levels of balance performance in an elderly, balance impaired cohort. C1 [Allin, Sonya J.; Mihailidis, Alex] Univ Toronto, Intelligent Assist Technol & Syst Lab, Toronto, ON, Canada. [Beach, Cheryl] Vancouver Island Hlth Author, Vancouver, BC, Canada. [Mihailidis, Alex] Natl Inst Hlth, Bethesda, MD USA. RP Allin, SJ (reprint author), Univ Toronto, Intelligent Assist Technol & Syst Lab, Toronto, ON, Canada. EM s.allin@utoronto.ca; alex.mihailidis@utoronto.ca OI Mihailidis, Alex/0000-0003-2233-0919 FU Vancouver Foundation; NSF RERC on Universal Design; Intramural Program of the NIH/NIMH FX This work was supported in part by the Vancouver Foundation, the NSF RERC on Universal Design and the Intramural Program of the NIH/NIMH NR 22 TC 6 Z9 6 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 4531 EP + DI 10.1109/IEMBS.2008.4650220 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404502329 ER PT S AU Sikdar, S Shah, JP Gilliams, E Gebreab, T Gerber, LH AF Sikdar, Siddhartha Shah, Jay P. Gilliams, Elizabeth Gebreab, Tadesse Gerber, Lynn H. GP IEEE TI Assessment of Myofascial Trigger Points (MTrPs): A New Application of Ultrasound Imaging and Vibration Sonoelastography SO 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY AUG 20-24, 2008 CL Vancouver, CANADA SP DEVICIX, Green Coll, Natl Inst Hlth, NIBIB, NSF, PLEXON Inc, UBC Engn Biomed Engn, Univ Washington, Coll Engn, Bentham Sci Publ Ltd, Recent Patents Biomed Engn, Recent Patents Engn ID PAIN AB Myofascial trigger points (MTrPs) are palpable hyperirritable nodules in skeletal muscle that are associated with chronic musculoskeletal pain. The goal of this study was to image MTrPs in the upper trapezius muscle using 2D gray scale ultrasound (US) and vibration sonoelastography (VSE) for differentiating the soft tissue characteristics of MTrPs compared to surrounding muscle. MTrPs appeared as hypoechoeic elliptically-shaped focal regions within the trapezius muscle on 2D US. Audio-frequency vibrations (100250 Hz) were induced in the trapezius muscle of four volunteers with clinically identifiable MTrPs, and the induced vibration amplitudes were imaged using the color Doppler variance mode, and were further quantified using spectral Doppler analysis. Spectral Doppler analysis showed that vibration amplitudes were 27% lower on average within the MTrP compared to surrounding tissue (p < 0.05). Color variance imaging consistently detected a focal region of reduced vibration amplitude, which correlated with the hypoechoeic region identified as an MTrP (r = 0.76 for area). Real-time 2D US identifies MTrPs, and VSE is feasible for differentiating MTrPs from surrounding tissue. Preliminary findings show that MTrPs are hypoechoeic on 2D US and the relative stiffness of MTrPs can be quantified using VSE. Ultrasound offers a convenient, accessible and low-risk approach for identifying MTrPs and for evaluating clinical observations of palpable, painful nodules. C1 [Sikdar, Siddhartha; Gerber, Lynn H.] George Mason Univ, Fairfax, VA 22030 USA. [Shah, Jay P.; Gilliams, Elizabeth; Gebreab, Tadesse] Natl Inst Hlth Clin Ctr, Bethesda, MD 20892 USA. RP Sikdar, S (reprint author), George Mason Univ, Fairfax, VA 22030 USA. EM ssikdar@gmu.edu OI Sikdar, Siddhartha/0000-0002-6426-2320 NR 14 TC 19 Z9 19 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-1814-5 J9 IEEE ENG MED BIO PY 2008 BP 5585 EP + DI 10.1109/IEMBS.2008.4650480 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BIS22 UT WOS:000262404503196 ER PT B AU Shroff, H Galbraith, CG Galbraith, JA White, H Gillette, J Olenych, S Davidson, MW Betzig, E AF Shroff, Hari Galbraith, Catherine G. Galbraith, James A. White, Helen Gillette, Jennifer Olenych, Scott Davidson, Michael W. Betzig, Eric GP IEEE TI Dual-Color Superresolution Imaging Using Genetically Expressed Probes SO 2008 CONFERENCE ON LASERS AND ELECTRO-OPTICS & QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE, VOLS 1-9 LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference (CLEO/QELS 2008) CY MAY 04-09, 2008 CL San Jose, CA ID PROTEIN AB We report dual-color superresolution imaging using endogenously expressed fluorescent proteins. An imaging resolution of 20-30 nm facilitates study of the ultrastructural relationship between proteins present in adhesion complexes at the surfaces of whole, fixed cells. C1 [Shroff, Hari; White, Helen; Betzig, Eric] Howard Hughes Med Inst, Jonelia Farm Res Campus, Ashburn, VA 20147 USA. [Galbraith, Catherine G.] NIH, Natl Inst Dental & Craniofacial Res, Bethesda, MD 20892 USA. [Galbraith, James A.] NIH, Natl Inst Neurolog Disorders & Stroke, Bethesda, MD 20892 USA. [Gillette, Jennifer] NIH, Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. [Olenych, Scott; Davidson, Michael W.] Florida State Univ, Dept Biolog Sci, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. RP Shroff, H (reprint author), Howard Hughes Med Inst, Jonelia Farm Res Campus, Ashburn, VA 20147 USA. EM shroffh@janelia.hhmi.org NR 5 TC 0 Z9 0 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-55752-859-9 PY 2008 BP 244 EP + PG 2 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BIL52 UT WOS:000260498400123 ER PT S AU Liu, JF Subramanian, K Yoo, T Van Uitert, R AF Liu, Jianfei Subramanian, Kalpathi Yoo, Terry Van Uitert, Robert GP IEEE TI A Stable Optic-Flow Based Method for Tracking Colonoscopy Images SO 2008 IEEE COMPUTER SOCIETY CONFERENCE ON COMPUTER VISION AND PATTERN RECOGNITION WORKSHOPS, VOLS 1-3 SE IEEE Conference on Computer Vision and Pattern Recognition LA English DT Proceedings Paper CT IEEE Conference on Computer Vision and Pattern Recognition CY JUN 23-28, 2008 CL Anchorage, AK SP IEEE Comp Soc ID MOTION; COMPUTATION; FIELD; ALGORITHM AB In this paper we focus on the robustness and stability of our algorithm to plot the position of an endoscopic camera (during a colonoscopy procedure) on the corresponding pre-operative CT scan of the patient. The colon has few topological landmarks, in contrast to bronchoscopy images, where a number of registration algorithms have taken advantage of features such as anatomical marks or bifurcations. Our method estimates the camera motion from the optic-flow computed from the information contained in the video stream. Optic-flow computation is notoriously susceptible to errors in estimating the motion field. Our method relies on the following features to counter this, (1) we use a small but reliable set of feature points (sparse optic-flow field) to determine the spatio-temporal scale at which to perform optic-flow computation in each frame of the sequence, (2) the chosen scales are used to compute a more accurate dense optic flow field, which is used to compute qualitative parameters relating to the main motion direction, and (3) the sparse optic-flow field and the main motion parameters are then combined to estimate the camera parameters. A mathematical analysis of our algorithm is presented to illustrate the stability, of our method, as well as comparison to existing motion estimation algorithms. We present preliminary results of using this algorithm on both a virtual colonoscopy image sequence, as well as a colon phantom image sequence. C1 [Liu, Jianfei; Subramanian, Kalpathi] Univ N Carolina, Charlotte, NC 28223 USA. [Yoo, Terry; Van Uitert, Robert] NIH, Natl Lib Med, Bethesda, MD USA. RP Liu, JF (reprint author), Univ N Carolina, Charlotte, NC 28223 USA. EM jliu1@uncc.edu; krs@uncc.edu; yoo@nlm.nih.gov; robert.vanuitert@gmail.com NR 37 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1063-6919 BN 978-1-4244-2339-2 J9 PROC CVPR IEEE PY 2008 BP 296 EP + PG 3 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Computer Science; Engineering; Imaging Science & Photographic Technology GA BIK29 UT WOS:000260371900041 ER PT S AU Zhang, JQ Wang, HH Suffredini, A Gonzales, D Gonzalez, E Huang, YF Zhou, XB AF Zhang, Jianqiu Wang, Honghui Suffredini, Anthony Gonzales, Denise Gonzalez, Elias Huang, Yufei Zhou, Xiaobo GP IEEE TI Bayesian peak detection for prO-TOF MS MALDI data SO 2008 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING, VOLS 1-12 SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT 33rd IEEE International Conference on Acoustics, Speech and Signal Processing CY MAR 30-APR 04, 2008 CL Las Vegas, NV DE mass spectrometry; proteomics; MALDI; peak detection; Bayesian methods AB In this paper, a novel Bayesian peak detection algorithm is proposed for peptide peak detection in high resolution prOTOF (TM) MALDI Mass Spectrometry(MS) data. A nonlinear parametric model is proposed for modeling the peptide signals, chemical noise, and thermal noise. A metropolized Gibbs sampling algorithm is derived for Bayesian peak detection. The proposed algorithm is compared with a popular wavelet-based algorithm and the results show a significant improvement in performance on simulated data. The algorithm is finally tested on real MS MALDI data and the results agree with visual inspection very well. C1 [Zhang, Jianqiu; Gonzalez, Elias; Huang, Yufei] Univ Texas San Antonio, Dept ECE, San Antonio, TX 78249 USA. [Huang, Yufei] Univ Texas San Antonio, Dept Bio Eng, San Antonio, TX 78249 USA. [Wang, Honghui; Suffredini, Anthony; Gonzales, Denise] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Huang, Yufei] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Zhou, Xiaobo] Texas Methodist Hosp Res Inst, Houston, TX 77030 USA. RP Zhang, JQ (reprint author), Univ Texas San Antonio, Dept ECE, San Antonio, TX 78249 USA. EM Michelle.Zhang@utsa.edu; xzhou@tmhs.org FU National Science Foundation [CCF-0546345] FX This work was supported by the National Science Foundation under Award CCF-0546345. NR 4 TC 2 Z9 3 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4244-1483-3 J9 INT CONF ACOUST SPEE PY 2008 BP 661 EP + PG 2 WC Acoustics; Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Engineering, Biomedical; Engineering, Electrical & Electronic; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging; Telecommunications SC Acoustics; Computer Science; Engineering; Mathematical & Computational Biology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging; Telecommunications GA BHY47 UT WOS:000257456700166 ER PT B AU Vigaru, B Petrisor, D Patriciu, A Mazilu, D Stoianovici, D AF Vigaru, B. Petrisor, D. Patriciu, A. Mazilu, D. Stoianovici, D. BE Miclea, L Stoian, I TI MR compatible actuation for medical instrumentation SO 2008 IEEE INTERNATIONAL CONFERENCE ON AUTOMATION, QUALITY AND TESTING, ROBOTICS (AQTR 2008), THETA 16TH EDITION, VOL III, PROCEEDINGS LA English DT Proceedings Paper CT IEEE International Conference on Automation, Quality and Testing, Robotics (AQTR 2008) CY MAY 22-25, 2008 CL Cluj Napoca, ROMANIA SP IEEE Comp Soc, TTTC ID PNEUMATIC ACTUATOR; SURGICAL ROBOTICS; SYSTEM; BIOPSY; VALVES; MOTOR AB Surgical robots and especially their subclass of image-guided systems require special design, construction and control compared to industrial types, due to the special requirements of the medical and imaging environments. Imager compatibility raises significant engineering challenges for the development of robotic manipulators with respect to imager access, safety, ergonomics, and above all the non-interference with the functionality of the imager. These apply to all known medical imaging types, but are especially challenging for achieving compatibility with the class of Magnetic Resonance Imaging (MRI) systems. Even though a large majority of robotic components may be redesigned to be constructed of MRI compatible materials, for other components such as the motors used in actuation, prescribing MRI compatible materials alone is not sufficient. The electromagnetic motors most commonly used in robotic actuation, for example, are incompatible by principle. We report here an important achievement in MRI instrumentation, a new type of pneumatic motor, PneuStep[1], specifically developed for MrBot, the first pneumatic, fully actuated MR robotic system that can be located within the scanner alongside the patient and operating under remote control based on the images. C1 [Vigaru, B.; Petrisor, D.; Stoianovici, D.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Patriciu, A.] McMaster Univ, Hamilton, ON, Canada. [Mazilu, D.] Natl Inst Hlth, Bethesda, MD USA. RP Vigaru, B (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. EM bogdan@jhu.edu; dpetris1@jhmi.edu; patriciu@mail.ece.mcmaster.ca; mazilud@mail.nih.gov; dss@jhu.edu NR 21 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-2576-1 PY 2008 BP 49 EP 52 DI 10.1109/AQTR.2008.4588880 PG 4 WC Automation & Control Systems; Engineering, Electrical & Electronic; Robotics SC Automation & Control Systems; Engineering; Robotics GA BIF23 UT WOS:000259080200003 ER PT S AU Yang, MQ Yang, JY AF Yang, Mary Qu Yang, Jack Y. BE Chen, Y He, J Reddy, CK Yang, J Yoo, I Zhang, X Gao, J Huang, Y Song, M Yang, J Wu, Z TI High-Performance Computing for Drug Design SO 2008 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE WORKSHOPS, PROCEEDINGS SE IEEE International Conference on Bioinformatics and Biomedicine Workshop-BIBMW LA English DT Proceedings Paper CT IEEE International Conference on Bioinformatics and Biomedicine CY NOV 03-05, 2008 CL Philadelphia, PA SP IEEE AB High performance computing has become a major focus of attention by government, industry, medical centers and academic institutions. The U.S. government has made this a "top national priority", linking the development of a "data superhighway system" to national competitiveness and national research interest. High performance supercomputing approaches have been used for sequence analysis, gene finding, protein structural prediction, all-atom simulation such as molecular dynamics and quantum calculations, modeling biological networks such as systems biology and more recently drug design and drug discovery. All these approaches are highly computationally demanding, in terms of compute load, communication speed, and memory load. Supercomputing based drug design and drug discovery use high-performance super-computers and bioinformatics approaches to discover, enhance, and study drugs and related biologically active molecules as well as the sites of protein interactions. Methods include molecular modeling using biophysical approaches such as molecular dynamics, semi-empirical quantum mechanics methods, ab initio quantum chemistry methods, density functional theory, receptor - ligand interactions and protein docking and so on. The success of the high-throughput drug design and drug discovery now directly relies on the high-performance computing capabilities. Many research and computational products that were used to be considered impossible now proved to be feasible and effective with the help of today's supercomputing techniques. In particular, the identification of diseases relating to protein structural changes challenges biomedicine as the result of the sophisticated protein interaction networks that demand effective drug design using supercomputing based on mathematical, computational and biophysical models and algorithms for solving the model equations, and the bioinformatics techniques to analyze and validate the results. Those will need our deeper studies of biophysical phenomena and interesting biophysical and algorithmic problems using supercomputing. In this keynote lecture, we follow the scenario of Koshland's "induced-fit" to demonstrate that the identification of intrinsically disordered/unstructured proteins will became increasingly important to the drug design and discovery, because many proteins are folding upon interaction with drugs. The High-performance computing approaches help to reduce the number of targets for a good drug that has to be eventually tested by expensive and time-consuming synthesis and laboratory and toxicology experiments. High-performance computing study of intrinsically unstructured protein related pathways focuses on the discovery and development of novel drugs for the treatment of metabolic and mis-folding related diseases by targeting the metabolic and biological pathways in the protein interaction network. The advances of supercomputing will foster the synergistic relation between biophysical and computational sciences towards translational bioinformatics in the future. C1 [Yang, Mary Qu] NHGRI, NIH, Bethesda, MD 20852 USA. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02140 USA. RP Yang, MQ (reprint author), NHGRI, NIH, Bethesda, MD 20852 USA. EM yangma@mail.NIH.gov; jyang@bwh.Harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 4 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2163-6966 BN 978-1-4244-2890-8 J9 IEEE INT C BIO BIO W PY 2008 BP 120 EP 120 DI 10.1109/BIBMW.2008.4686222 PG 1 WC Engineering, Biomedical SC Engineering GA BIQ62 UT WOS:000262067000021 ER PT S AU Wang, ZS Maier, A Logothetis, NK Liang, HL AF Wang, Zhisong Maier, Alexander Logothetis, Nikos K. Liang, Hualou GP IEEE TI Single-Trial Bistable Perception Classification Based on Sparse Nonnegative Tensor Decomposition SO 2008 IEEE INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS, VOLS 1-8 SE IEEE International Joint Conference on Neural Networks (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks CY JUN 01-08, 2008 CL Hong Kong, PEOPLES R CHINA SP IEEE ID PARALLEL FACTOR-ANALYSIS; MATRIX FACTORIZATION; VISUAL RESPONSES; FIELD POTENTIALS; EEG; UNIQUENESS; ARRAYS; CHOICE AB The study of the neuronal correlates of the spontaneous alternation in perception elicited by bistable visual stimuli is promising for understanding the mechanism of neural information processing and the neural basis of visual perception and perceptual decision-making. In this paper we apply a sparse nonnegative tensor factorization (NTF) based method to extract features from the local field potential (LFP) in monkey visual cortex for decoding its bistable structure-from-motion (SFM) perception. We apply the feature extraction approach to the multichannel time-frequency representation of intracortical UP data collected from the middle temporal area (MT) in a macaque monkey performing a SFM task. The advantages of the sparse NTF based feature extraction approach lies in its capability to yield components common across the space, time and frequency domains and at the same time discriminative across different conditions without prior knowledge of the discriminative frequency bands and temporal windows for a specific subject. We employ the support vector machines (SVM) classifier based on the features of the NTF components to decode the reported perception on a single-trial basis. Our results suggest that although other bands also have certain discriminability, the gamma band feature carries the most discriminative information for bistable perception, and that imposing the sparseness constraints on the nonnegative tensor factorization improves extraction of this feature. C1 [Wang, Zhisong; Liang, Hualou] Univ Texas Houston, Hlth Sci Ctr, Sch Hlth Informat Sci, 7000 Fannin,Suite 600, Houston, TX 77030 USA. [Maier, Alexander] NIH, Unit Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA. [Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. RP Liang, HL (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Hlth Informat Sci, 7000 Fannin,Suite 600, Houston, TX 77030 USA. EM Zhi-Song.Wang@uth.tmc.edu; maiera@mail.nih.gov; nikos.logothetis@tuebingen.mpg.de; Hualou.Liang@uth.tmc.edu RI Maier, Alexander/B-7489-2009 OI Maier, Alexander/0000-0002-7250-502X FU NIH [NS054314, MH072034] FX This work was supported in part by the NIH R01 NS054314 and R01 MH072034. NR 34 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2161-4393 BN 978-1-4244-1820-6 J9 IEEE IJCNN PY 2008 BP 1041 EP 1048 DI 10.1109/IJCNN.2008.4633927 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BIY81 UT WOS:000263827200170 ER PT S AU Linguraru, MG Summers, RM AF Linguraru, Marius George Summers, Ronald M. GP IEEE TI Multi-organ automatic segmentation in 4D contrast-enhanced abdominal CT SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE abdominal imaging; liver; spleen; kidneys; segmentation; registration; contrast-enhanced CT AB Medical imaging and computer-aided diagnosis (CAD) traditionally focus on organ- or disease-based applications. To shift from organ-based to organism-based approaches, CAD needs to replicate the work of radiologists and analyze consecutively multiple organs. A fully automatic method is presented for the simultaneous segmentation of four abdominal organs from 4D CT data. Abdominal contrast-enhanced CT scans from sixteen patients were obtained at three phases: non-contrast, arterial and portal. Intrapatient data is registered non-rigidly using the demons algorithm and smoothed with anisotropic diffusion. Mutual information accounts for intensity variability within the same organ during subsequent acquisitions and data are interpolated with cubic B-splines. Then heterogeneous erosion is applied to multi-phase data using the intensity characteristics of the liver, spleen, and kidneys. The erosion filter is a 4D convolution that preserves only image regions that satisfy the above intensity criteria. Finally, a geodesic level set completes the segmentation of the four abdominal organs. This 3D evaluation of abdominal data shows great promise as a computer-aided radiology tool for multi-organ and multi-disease analysis. C1 [Linguraru, Marius George] Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD USA. [Linguraru, Marius George; Summers, Ronald M.] Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD USA. RP Linguraru, MG (reprint author), Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD USA. EM lingurarum@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, Clinical Center FX This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center NR 11 TC 12 Z9 12 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 45 EP + DI 10.1109/ISBI.2008.4540928 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800012 ER PT S AU Butman, JA Linguraru, MG AF Butman, John A. Linguraru, Marius George GP IEEE TI Assessment of ventricle volume from serial MRI scans in communicating hydrocephalus SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE brain imaging; MRI; brain tumor; hydrocephalus; segmentation; registration; monitoring ID NONRIGID REGISTRATION; SEGMENTATION; IMAGES; BRAIN AB Postoperative communicating hydrocephalus has been recognized in patients with brain tumors. The associated changes in ventricle volume can be difficult to identify, particularly over short time intervals. Potentially, accurate ventricle volume estimates could provide for a better understanding of communicating hydrocephalus, and lead to more confident diagnoses. Our method evaluates ventricle size from serial brain MRI examinations, we 1) combined serial images to increase SNR 2) segmented this image to generate a ventricle template using fats marching methods and geodesic active contours, and 3) propagate the segmentation using deformable registration of the original MRI datasets. By applying this deformation to the ventricle template, serial volume estimates were obtained in a robust manner. C1 [Butman, John A.; Linguraru, Marius George] Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD USA. RP Butman, JA (reprint author), Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD USA. EM lingurarum@mail.nih.gov OI Butman, John/0000-0002-1547-9195 FU Intramural Research Program of the National Institutes of Health, Clinical Center FX This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. NR 10 TC 4 Z9 4 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 49 EP + DI 10.1109/ISBI.2008.4540929 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800013 ER PT S AU Wan, J Carass, A Resnick, SM Prince, JL AF Wan, Jing Carass, Aaron Resnick, Susan M. Prince, Jerry L. GP IEEE TI AUTOMATED RELIABLE LABELING OF THE CORTICAL SURFACE SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE brain; image segmentation; image registration; biomedical image processing ID BRAIN; SEGMENTATION; THICKNESS; ADULTS AB Accurate and reliable labeling of regions of interest (ROIs) within structural magnetic resonance images (MRIs) is an important step in group analysis. Group registration does not always yield accurate alignment of homologous regions. We present an approach that distinguishes itself from other algorithms by being concerned with a label which is of the highest fidelity, while leaving ambiguous regions unlabeled. Regions that are not deemed to be reliably labeled are not included in group statistics. We will present results showing that our method is an improvement over traditional multi-atlas voting schemes. We conclude with a pilot study of longitudinal trends of cortical thickness in normal aging. C1 [Wan, Jing; Carass, Aaron; Prince, Jerry L.] Johns Hopkins Univ, Image Anal & Commun Lab, Baltimore, MD 21218 USA. [Resnick, Susan M.] Natl Inst Health, Natl Inst Aging, Bethesda, MD USA. RP Wan, J (reprint author), Johns Hopkins Univ, Image Anal & Commun Lab, Baltimore, MD 21218 USA. EM jingwan@jhu.edu; aaron_carass@jhu.edu; resnicks@grc.nia.nih.gov; prince@jhu.edu RI Prince, Jerry/A-3281-2010; OI Prince, Jerry/0000-0002-6553-0876; Carass, Aaron/0000-0003-4939-5085 FU NIH/NINDS [R01 NS37747, R01 NS052585-01]; Intramural Research Program, National Institute on Aging, NIH; NCRR [P41-RR14075, R01 RR16594-01A1] FX This work was supported by the NIH/NINDS under grant R01 NS37747 and in part by the Intramural Research Program, National Institute on Aging, NIH. Data was provided by Dr. B. Fischl, Martinos Center for Biomedical Imaging, and supported by the NCRR through grants P41-RR14075 and R01 RR16594-01A1 and by the NIH/NINDS through grant R01 NS052585-01. NR 19 TC 5 Z9 5 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 440 EP + PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800111 ER PT S AU Gavrielides, MA Masmoudi, H Petrick, N Myers, KJ Hewitt, SM AF Gavrielides, Marios A. Masmoudi, Hela Petrick, Nicholas Myers, Kyle J. Hewitt, Stephen M. GP IEEE TI Automated evaluation of HER-2/neu immunohistochemical expression in breast cancer using digital microscopy SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE microscopy imaging; immunohistochemistry; biomarker imaging; HER2/neu; computer aided analysis ID AMPLIFICATION; CARCINOMA; ONCOGENE AB HER-2/neu (HER2) has been shown to be a valuable biomarker for breast cancer. However, inter-observer variability has been reported in the evaluation of HER2 with immunohistochemistry. It has been suggested that automated computer-based evaluation can provide a consistent and objective measure of HER2 expression. In this manuscript, we present an automated method for the quantitative assessment of HER2 using digital microscopy. The method employs imaging algorithms on whole slide images of tissue specimens for the extraction of two features describing HER2 membrane staining, namely membrane staining completeness and membrane staining intensity. A classifier was trained to merge the extracted features into an overall slide assessment score. Preliminary results showed good agreement with the provided truth. The developed automated method has the potential to be used as a computer aid for the immunohistochemical evaluation of HER2 expression with the objective of increasing observer reproducibility. C1 [Gavrielides, Marios A.; Masmoudi, Hela; Petrick, Nicholas; Myers, Kyle J.] NIBIB, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, USDA, Washington, DC 20052 USA. [Masmoudi, Hela] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. [Hewitt, Stephen M.] Natl Inst Hlth, Tissue Array Res Program, Ctr Canc Res, Natl Canc Inst, Bethesda, MD 20892 USA. RP Gavrielides, MA (reprint author), NIBIB, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, USDA, Washington, DC 20052 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 8 TC 7 Z9 7 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 808 EP + DI 10.1109/ISBI.2008.4541119 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800203 ER PT S AU Peterhans, M Talib, H Linguraru, MG Styner, M Ballester, MAG AF Peterhans, Matthias Talib, Haydar Linguraru, Marius G. Styner, Martin Ballester, Miguel A. Gonzalez GP IEEE TI A method for frame-by-frame US to CT registration in a joint calibration and registration framework SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE point-to-surface registration; Kalman filtering; ultrasound; computer-assisted surgery; calibration ID ULTRASOUND; VALIDATION AB A method is presented for achieving robust joint calibration and registration in ultrasound (US) to CT registration for computer assisted orthopedic surgery. We propose using an effectively real-time frame-by-frame registration algorithm during US image acquisition. This approach provides more control to the surgeon, is more robust to initial conditions, and is computationally efficient. We then use the estimated registration of the frame-by-frame method to initialize a joint calibration and registration algorithm, and this is shown to produce over all more accurate and repeatable results. Experiments are performed using simulated US images of the lumbar vertebra and the distal femur as potential areas of interest for surgical applications. C1 [Peterhans, Matthias; Talib, Haydar; Ballester, Miguel A. Gonzalez] Univ Bern, Inst Surg Technol & Biomech, MEM Res Ctr, CH-3012 Bern, Switzerland. [Linguraru, Marius G.] NIH, Dept Clin Radiotherapy, Bethesda, MD USA. [Styner, Martin] Univ North Crolina, Dept Comp Sci & psyhiat, Chapel Hill, NC USA. RP Peterhans, M (reprint author), Univ Bern, Inst Surg Technol & Biomech, MEM Res Ctr, CH-3012 Bern, Switzerland. RI Gonzalez Ballester, Miguel Angel/D-1349-2013; OI Gonzalez Ballester, Miguel Angel/0000-0002-9227-6826; Gonzalez Ballester, Miguel Angel/0000-0002-1862-9590 FU NCCR Co-Me; BrainLab AG; AO Foundation FX The authors wish to thank the NCCR Co-Me, BrainLab AG and the AO Foundation for funding this project. NR 10 TC 7 Z9 7 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 1131 EP + DI 10.1109/ISBI.2008.4541200 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800284 ER PT S AU Hsu, LY Aletras, AH Arai, AE AF Hsu, Li-Yueh Aletras, Anthony H. Arai, Andrew E. GP IEEE TI Correcting surface coil intensity inhomogeneity improves quantitative analysis of cardiac magnetic resonance images SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE biomedical image processing; magnetic resonance imaging; cardiovascular system AB Quantitative analysis of cardiac magnetic resonance (MR) images is important in bringing objectivity in diagnosis of myocardial abnormalities. Prior to quantitative analysis, it is necessary to correct signal intensity inhomogeneity due to the non-uniform surface coil sensitivity profile. We present a method using non-rigid body image warping and polynomial function fitting to correct this intensity bias on imperfectly registered cardiac MR images. The method was validated on normal human MR images and significantly reduced signal variation from 20.0% to 3.9% in regions of normal myocardium. In MR images of acute myocardial infarction in dogs, signal intensity analysis detected edematous myocardium as 35.9% brighter than normal myocardium on T2-weighted images (p=0.002) while control regions of interest on PD-weighted images were uniform within 2.2% (p=NS). The proposed approach effectively corrected surface coil related signal intensity inhomogeneity in imperfect datasets and allowed confident detection of subtle pathophysiological abnormalities. C1 [Hsu, Li-Yueh; Aletras, Anthony H.; Arai, Andrew E.] NHLBI, Dept Hlth & Human Serv, NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Hsu, LY (reprint author), NHLBI, Dept Hlth & Human Serv, NIH, Cardiac Energet Lab, Bldg 10, Bethesda, MD 20892 USA. OI Aletras, Anthony/0000-0002-3786-3817 NR 3 TC 4 Z9 4 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 1425 EP 1428 DI 10.1109/ISBI.2008.4541274 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800358 ER PT S AU George, AK Butala, MD Frazin, RA Kamalabadi, F Bresler, Y AF George, A. K. Butala, M. D. Frazin, R. A. Kamalabadi, F. Bresler, Y. GP IEEE TI Time-resolved cardiac CT reconstruction using the ensemble Kalman Filter SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE cardiac; dynamic tomography; time-resolved; computed tomography; Kalman Filter AB We propose an algorithm to solve the problem of Time-Resolved Cardiac Computed Tomography (CT). The algorithm reconstructs a snapshot of the moving heart at any time instant from CT projection data acquired over a single heart-cycle. The object is modeled by a spatio-temporal state-space model, and an ensemble Kalman Filter (a Monte-Carlo approximation to the Kalman filter) is used to assimilate the sequentially acquired projection data. Simulation results of the dynamic NCAT cardiac phantom, under the fan-beam geometry and a two-source CT system, show reconstructions that are free of the motion artifacts that mar conventional methods. C1 [George, A. K.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Butala, M. D.; Frazin, R. A.; Kamalabadi, F.; Bresler, Y.] Univ Illinois, Dept ECE, Urbana, IL 61801 USA. [Butala, M. D.; Frazin, R. A.; Kamalabadi, F.; Bresler, Y.] Univ Illinois, Coordinated Sci Lab, Urbana, IL 61801 USA. RP George, AK (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Frazin, Richard/J-2625-2012 FU Research Board at the University of Illinois at Urbana-Champaign FX This research was partly supported by the Research Board at the Univer- sity of Illinois at Urbana-Champaign. NR 6 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 1489 EP + DI 10.1109/ISBI.2008.4541290 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800374 ER PT B AU Chen, Y Yang, F Meltzer, PS AF Chen, Yidong Yang, Fan Meltzer, Paul S. GP IEEE TI Application of gene set enrichment method to ChIP-chip data analysis SO 2008 IEEE INTERNATIONAL WORKSHOP ON GENOMIC SIGNAL PROCESSING AND STATISTICS LA English DT Proceedings Paper CT IEEE International Workshop on Genomic Signal Processing and Statistics CY JUN 08-10, 2008 CL Phoenix, AZ SP IEEE ID BREAST-CANCER; EXPRESSION; SURVIVAL AB To elucidate biological functions from gene expression profiles, gene set enrichment analysis (GSEA) is widely applied against sets of predefined genes that may yield crucial clues to their functional themes or regulatory information. However, gene list derived from array-based chromatin-immunoprecipitation (ChIP-chip) experiments, where a genes with one or more binding sites of a given protein, possesses different characteristics than that from gene expression profiles: genes are not rank-ordered by their differential expression, but rather associated with a genomic distance to its nearest binding site from the transcription start site (TSS). In this study, we proposed a unique binding-site enrichment analysis method that enabled enrichment analysis of gene list derived from whole-genome ChIEP-chip experiment to gene expression data set, such as a panel of normal tissue gene expression profiles or some cancer-related expression profiles, in order to identify the essential regulatory role of the transcription factor under study. C1 [Chen, Yidong; Yang, Fan; Meltzer, Paul S.] NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. RP Chen, Y (reprint author), NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-2371-2 PY 2008 BP 99 EP 101 PG 3 WC Engineering, Electrical & Electronic; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BIC55 UT WOS:000258398200032 ER PT S AU Zhu, BP Wu, DW Zhou, QF Shung, KK AF Zhu, B. P. Wu, D. W. Zhou, Q. F. Shung, K. K. GP IEEE TI Lead zirconate titanate thick film with enhanced electrical properties for high frequency transducer applications SO 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX SE Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY NOV 02-05, 2008 CL Beijing, PEOPLES R CHINA SP IEEE ID COMPOSITE; MHZ AB Piezoelectric Pb(Zr0.52Ti0.48)O-3 thick film with the thickness around 10 gm has been deposited on the (111) Pt/Ti/SiO2/Si substrate using a ceramic power/sol-gel solution modified composite method. X-ray diffraction analysis and scanning electron microscope revealed that the film was in the well-crystallized perovskite phase and cracked free. At 1 KHz, The dielectric constant and the loss were 1925 and 0.015, respectively. The remnant polarization was 42.0 mu C/cm(2) at room temperature. A high frequency single element acoustic transducer fabricated with this film showed a bandwidth at -6 dB of 50% at 156 MHz. C1 [Zhu, B. P.; Wu, D. W.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, NIH Transducer Resource Ctr, Dept Biomed Engn, Los Angeles, CA 90089 USA. RP Zhu, BP (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Dept Biomed Engn, Los Angeles, CA 90089 USA. FU NIH [P41-EB2182] FX This research was supported by NIH grant P41-EB2182. NR 15 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-2428-3 J9 ULTRASON PY 2008 BP 70 EP + DI 10.1109/ULTSYM.2008.0018 PG 2 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BKP07 UT WOS:000268845800018 ER PT S AU Peng, J Lau, ST Chao, C Dai, JY Chan, HLW Lu, HS Zhou, QF Shung, KK AF Peng, Jue Lau, Sienting Chao, Chen Dai, Jiyan Chan, Helen L. W. Lu, Haosu Zhou, Q. F. Shung, K. K. GP IEEE TI PMN-PT single crystal thick films on silicon substrate for high-frequency micromachined ultrasonic transducers SO 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX SE Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY NOV 02-05, 2008 CL Beijing, PEOPLES R CHINA SP IEEE DE PMN-PT; pMUT; ultrasound transducer ID MEDICAL IMAGING APPLICATIONS; ARRAY AB In this work, a novel high-frequency ultrasonic transducer structure is realized by using PMNPT-on-silicon technology and silicon micromachining. To prepare the single crystalline PMNPT-on-silicon wafers, a hybrid processing method involving wafer bonding, mechanical lapping and wet chemical thinning is successfully developed. The active element is fixed within the stainless steel needle housing. The measured center frequency and -6 dB bandwidth of the transducer are 35 MHz and 34%, respectively. Owing to the excellent electromechanical property of PMNPT film, the transducer shows good energy conversion performance with a very low insertion loss down to 8.3 dB at the center frequency. C1 [Peng, Jue; Lau, Sienting; Chao, Chen; Dai, Jiyan; Chan, Helen L. W.] Hong Kong Polytech Univ, Dept Appl Phys, Mat Res Ctr, Hong Kong, Hong Kong, Peoples R China. [Lu, Haosu] Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab Performance Ceram, Shanghai 201800, Peoples R China. [Zhou, Q. F.; Shung, K. K.] Univ So Calif, NIH, Dept Biomed Engn, Los Angeles, CA 90089 USA. RP Dai, JY (reprint author), Hong Kong Polytech Univ, Dept Appl Phys, Mat Res Ctr, Hong Kong, Hong Kong, Peoples R China. EM apdaijy@inet.polyu.edu.hk RI Lau, Sien-Ting/B-6091-2013; CHAN, Helen Lai Wa/B-5633-2014 OI CHAN, Helen Lai Wa/0000-0002-8508-3049 FU Innovation and Technology Fund [ITS/037/07] FX Financial support from the Innovation and Technology Fund (ITS/037/07) is acknowledged. NR 14 TC 0 Z9 0 U1 1 U2 8 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-2428-3 J9 ULTRASON PY 2008 BP 161 EP + DI 10.1109/ULTSYM.2008.0039 PG 2 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BKP07 UT WOS:000268845800039 ER PT S AU Chen, GS Chang, H Liu, RB Shung, KK AF Chen, Gin-Shin Chang, Hsu Liu, Ruibin Shung, K. Kirk GP IEEE TI Development of 1.5D Cylindrical HIFU Phased Array SO 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX SE Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY NOV 02-05, 2008 CL Beijing, PEOPLES R CHINA SP IEEE DE HIFU phased array; 1-3 piezocamposites; 1.5D dynamic focusing ID LIVER; ULTRASOUND; MOTION AB High intensity focused ultrasound, HIFU has been used to non-invasively treat human tumors, such as uterine fibroids, prostate cancer, breast cancer, liver tumor, and brain tumor. However, the tumor in some organs can be moved by human breathing and heart beat, which may cause the ablation and damage of normal tissues during the sonication of HIFU. The purpose of this study was to develop a HIFU phased array for tracking the moving tumors. In the initial design, the array had a center frequency of 1.0 MHz and 512 elements that allowed symmetric control. PZT4 1-3 composites were formed via the "dice and fill" technology and then shaped into a cylindrical structure. The results simulated by Field II demonstrated that the array in water had a dynamic focusing range from 145 mm to 175 mm in Depth and a steering range from -15 mm to 15 mm in azimuthal direction with respect to the center of the array. A prototype of the array was fabricated. The aperture of the array was 15 cm by 12 cm and the radius of curvature was 15 cm. The impedance of each channel (a pair of elements) was measured and the average was 1500 Ohm. Surface acoustic intensity up to 12.6 W/cm(2) was applied to one piece of cylindrical PZT4-composite consisting of 22 elements for 50 minutes, and the temperature of the composite was not observed to rise appreciably. A 256-channel amplifier was utilized to drive the array without impedance matching in water and the water spring was observed at the natural focus of the array when the driving signal to each channel was zero-phase at 0.9MHz. The phase control and impedance matching circuits for each channel are being designed. C1 [Chen, Gin-Shin; Chang, Hsu] Natl Hlth Res Inst, Div Med Engn Res, Zhunan, Taiwan. [Liu, Ruibin; Shung, K. Kirk] Univ Southern Calif, NIH, Ultrasound Trans Resource Ctr, Dept Biomed Engn, Los Angeles, CA 90007 USA. RP Chen, GS (reprint author), Natl Hlth Res Inst, Div Med Engn Res, Zhunan, Taiwan. EM gschen@nhri.org.tw RI Chen, Gin-Shin /E-3988-2010; Chang, Hsu /E-3971-2010; OI Chen, Gin-Shin/0000-0003-3368-7470 NR 11 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-2428-3 J9 ULTRASON PY 2008 BP 792 EP + DI 10.1109/ULTSYM.2008.0190 PG 2 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BKP07 UT WOS:000268845800190 ER PT S AU Wu, DW Zhou, QF Shung, KK Liu, CG Djuth, FT AF Wu, D. W. Zhou, Q. F. Shung, K. K. Liu, C. G. Djuth, F. T. GP IEEE TI High-frequency Piezoelectric PZT Film Micromachined Ultrasonic Arrays SO 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX SE Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY NOV 02-05, 2008 CL Beijing, PEOPLES R CHINA SP IEEE DE PZT film; High-frequency; Micromachined; Linear array ID TRANSDUCERS; CERAMICS; MHZ AB This paper presents the latest development of high-frequency PZT film ultrasonic linear arrays. A PZT thick film of 22 pm in thickness was fabricated with a spin-coating method. The film was found to have a remnant polarization of 30 mu C/cm(2) and a coercive field Ec of 70 KV/cm. A high-frequency linear array was successfully fabricated with the film. The array shows a center frequency of 80 MHz and a bandwidth (-6 dB) of 80% with a layer of parylene as the matching. Measured results also show that the array has an insertion loss of -41 dB and a crosstalk of -25 dB at the center frequency. C1 [Wu, D. W.; Zhou, Q. F.; Shung, K. K.] Univ Southern Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Liu, C. G.; Djuth, F. T.] Geospace Res Inc, El Segundo, CA 90245 USA. RP Wu, DW (reprint author), Univ Southern Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. FU NIH [P41-EB2182]; NIH/NCI [2R44CA110214] FX This work was supported by NIH Grant #P41-EB2182 and NIH/NCI 2R44CA110214. The authors would like to thank Mr. Benpeng Zhu and Mr. Jay Williams for their aid with the film and transducer fabrication process. NR 13 TC 3 Z9 3 U1 1 U2 5 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-2428-3 J9 ULTRASON PY 2008 BP 1222 EP + DI 10.1109/ULTSYM.2008.0295 PG 2 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BKP07 UT WOS:000268845800295 ER PT S AU Zhang, LQ Xu, XC Hu, CH Sun, L Yen, JT Cannata, JM Shung, KK AF Zhang, Lequan Xu, Xiaochen Hu, Changhong Sun, Lei Yen, Jesse T. Cannata, Jonathan M. Shung, K. Kirk GP IEEE TI Improved high-frequency high frame rate duplex ultrasound linear array imaging system SO 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX SE Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY NOV 02-05, 2008 CL Beijing, PEOPLES R CHINA SP IEEE AB In this paper, we report recent progress that has been made in the development of a high frame rate duplex HF ultrasound system with both B-scan imaging and Doppler flow measurements. A 32-channel HF analog beamformer module with transmitting focusing and dynamic focusing on reception was implemented. High-speed timing circuits were used to achieve high imaging frame rate by reducing the acquisition overhead. Therefore, the frame rate of the system relies only on the field of view. The system also included a 64-channel analog front-end pulser/receiver, a HF pulsed-wave (PW) Doppler module, a PC with a 200MS/s 14-bit PCI A/D card and real-time Labview software for data acquisition and image display. A wire phantom used to evaluate the resolution of the system. High frame rate B-scan images of mouse hearts have been obtained, as well as the PW Doppler blood flow velocity profiles at the specified location. The system is able to acquire real-time B-mode images at a rate greater than 400 frames per second in a 4.8 x 13 mm field of view. In vivo mouse experiment results show a promising future of this system in small animal research. The system will be expanded to support future arrays with more elements. C1 [Zhang, Lequan; Hu, Changhong; Yen, Jesse T.; Cannata, Jonathan M.; Shung, K. Kirk] Univ Southern Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Xu, Xiaochen] Texas Instruments Inc, Med Business Unit, Dallas, TX 75243 USA. [Sun, Lei] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Kowloon, Hong Kong, Peoples R China. RP Zhang, LQ (reprint author), Univ Southern Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. EM lequanzh@usc.edu FU National Institute of Health (NIH) [P41-EB002182, R01HL079976] FX The authors would like to thank the National Institute of Health (NIH) for providing the funding for this work through grants # P41-EB002182, R01HL079976. NR 10 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-2428-3 J9 ULTRASON PY 2008 BP 1730 EP + DI 10.1109/ULTSYM.2008.0424 PG 3 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BKP07 UT WOS:000268845801016 ER PT S AU Yang, HC Yin, JC Hu, CH Zhou, QF Cannata, J Chen, ZP Shung, KK AF Yang, Hao-Chung Yin, Jiechen Hu, Changhong Zhou, Qifu Cannata, Jonathan Chen, Zhongping Shung, K. Kirk GP IEEE TI Novel biomedical imaging that combines intravascular ultrasound (IVUS) and optical coherence tomography (OCT) SO 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX SE Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY NOV 02-05, 2008 CL Beijing, PEOPLES R CHINA SP IEEE DE Intravascular ultrasound; IVUS; Optical coherence tomography; OCT; PMN-PT ID SINGLE-CRYSTAL; PROBE AB We have developed a new biomedical imaging probe combining intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Pb(Mg1/3Nb2/3)O-3-PbTiO3 (PMN-PT) needle ultrasound transducers with an aperture size of 0.6 mm were fabricated. The measured center frequency and -6 dB fractional bandwidth of the PMN-PT needle ultrasound transducer were 35 MHz and 60 %, respectively. A mirror was mounted at the tip of the probe at position 45 degrees to change the propagation direction of the ultrasound beam and the laser beam. In vitro images of rabbit trachea and aorta forming from this combined probe have been acquired. These results demonstrate that the complementary nature of these two modalities may yield beneficial results that could not be obtained otherwise. C1 [Yang, Hao-Chung; Hu, Changhong; Zhou, Qifu; Cannata, Jonathan; Shung, K. Kirk] Univ Southern Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Yin, Jiechen; Chen, Zhongping] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA. RP Yang, HC (reprint author), Univ Southern Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. EM yangh@usc.edu NR 11 TC 3 Z9 3 U1 2 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-2428-3 J9 ULTRASON PY 2008 BP 1769 EP + DI 10.1109/ULTSYM.2008.0434 PG 2 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BKP07 UT WOS:000268845801026 ER PT S AU Chan, TH Chen, L Choyke, PL Chi, CY Wang, Y AF Chan, Tsung-Han Chen, Li Choyke, Peter L. Chi, Chong-Yung Wang, Yue GP IEEE TI CONVEX ANALYSIS FOR SEPARATION OF FUNCTIONAL PATTERNS IN DCE-MRI: A LONGITUDINAL STUDY TO ANTIANGIOGENIC THERAPY SO 2008 IEEE WORKSHOP ON MACHINE LEARNING FOR SIGNAL PROCESSING SE IEEE Workshop on Machine Learning for Signal Processing LA English DT Proceedings Paper CT IEEE Workshop on Machine Learning for Signal Processing CY OCT 16-19, 2008 CL Cancun, MEXICO SP IEEE Signal Proc Soc, IEEE DE Blind source separation; compartment latent variable model; convex analysis; dynamic contrast-enhanced magnetic resonance imaging; antiangiogenic therapy ID COMPONENT ANALYSIS; ALGORITHM AB Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can characterize vascular heterogeneity, and has potential utility in assessment of the efficacy of angiogenesis inhibitors in cancer treatment. Due to the heterogeneous nature of tumor microvasculature, the measured signals can be represented as the mixture of the permeability images corresponding to different perfusion rates. We recently reported a hybrid convex analysis of mixture framework for unmixing of non-negative yet dependent angiogenic permeability distributions (APDs) and perfusion time activity curves (TACs). In our last work, we presented an underlying theory to infer the concept that the TACs can be identified by Finding the lateral edges of an observation-constructed convex pyramid when the well-grounded points exist for all APDs. For fulfilling this concept, a hybrid method including non-negative clustered component analysis, convex analysis, and least-squares fitting with non-negativity constraints was developed. In this paper, we use computer simulations to validate the performance of our reported framework, and further apply it to three sets of real DCE-MRI data, before and during the treatment period, for assessing the response to antiangiogenic therapy. The experimental results are not only surprisingly meaningful in biology and clinic, but also capable of reflecting the efficacy of angiogenesis inhibitors in cancer treatment. C1 [Chan, Tsung-Han; Chen, Li; Wang, Yue] Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Blacksburg, VA 24061 USA. [Chan, Tsung-Han; Chi, Chong-Yung] Natl Tsing Hua Univ, Inst Commun Eng, Dept Elect Engn, Hsinchu, Taiwan. [Choyke, Peter L.] NIH, Natl Cancer Inst, Mol Imaging Prog, Bethesda, MD USA. RP Chan, TH (reprint author), Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Blacksburg, VA 24061 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1551-2541 BN 978-1-4244-2375-0 J9 MACHINE LEARN SIGN P PY 2008 BP 261 EP + DI 10.1109/MLSP.2008.4685490 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BJK47 UT WOS:000266687900045 ER PT S AU Komatsoulis, GA AF Komatsoulis, George A. GP IEEE TI caBIG (TM):Opportunities and Challenges to creating a federated global network of interoperable information systems SO 8TH IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOENGINEERING, VOLS 1 AND 2 SE IEEE International Conference on Bioinformatics and Bioengineering LA English DT Proceedings Paper CT 8th IEEE International Conference on Bioinformatics and Bioengineering CY OCT 08-10, 2008 CL Athens, GREECE SP IEEE Syst, Man & Cybernet Soc AB The cancer Biomedical Informatics Grid (caBIG (TM)) was initiated by the US National Cancer Institute in 2004 to address the need for interoperable information systems to enable molecular medicine for oncology. With the successful completion of the pilot phase of caBIG (TM) in 2007, the NCI is in the process of expanding the program into the broader biomedical research and care delivery arena. To accomplish this goal it is necessary to address a series of challenges associated with common semantics, security, interoperability standards and politics. A partnership between caBIG (TM) and the UK National Cancer Research Institute (NCRI) is providing an initial model for addressing these challenges more globally. C1 NCI, CBIIT, Rockville, MD 20852 USA. RP Komatsoulis, GA (reprint author), NCI, CBIIT, 2115 E Jefferson St,Suite 6000, Rockville, MD 20852 USA. EM komatsog@mail.nih.gov NR 9 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2471-7819 BN 978-1-4244-2844-1 J9 IEEE INT C BIOINF BI PY 2008 BP 388 EP 393 PG 6 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Medical Informatics SC Engineering; Medical Informatics GA BIY90 UT WOS:000263828500065 ER PT J AU Couture, S Brown, TG Ouimet, MC Gianoulakis, C Tremblay, J Carbonneau, R AF Couture, Sophie Brown, Thomas G. Ouimet, Marie Claude Gianoulakis, Christina Tremblay, Jacques Carbonneau, Rene TI Hypothalamic-pituitary-adrenal axis response to stress in male DUI recidivists SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE driving while impaired; repeat offenders; cortisol; alcohol use; sensation seeking; antisocial features ID PLATELET MONOAMINE-OXIDASE; SALIVARY CORTISOL CONCENTRATIONS; BETA-ENDORPHIN; GENDER-DIFFERENCES; SENSATION SEEKING; TIMELINE FOLLOWBACK; PERSONALITY-TRAITS; SOBER ALCOHOLICS; IMPAIRED DRIVERS; MAO ACTIVITY AB Cortisol is a stress hormone mediated by the hypothalamic-pituitary-adrenal (HPA) axis and a psychobiological marker of genetic risk for alcoholism and other high-risk behavioural characteristics. In previous work with driving under the influence of alcohol (DUI) recidivists, we uncovered a significant inverse relationship between the frequency of past DUI convictions and salivary cortisol, whose strength surpassed those observed between DUI frequency and measures of alcohol abuse and other DUI-related characteristics. This finding emerged using a methodology not specifically contrived to test this relationship. The goals of this follow-up study were to (a) examine if a standardized stress-induction protocol would produce a significant inverse relationship between cortisol response and number of DUI offences; and (b) clarify whether HPA axis dysregulation could be linked to particular DUI-related behavioural correlates, such as alcohol use severity, sensation seeking, and antisocial features. Thirty male DUI recidivists were recruited as well as I I male non-DUI drivers as a comparison group. Results indicated an inverse relationship between DUI frequency and cortisol response (r(39) = -0.36, p = 0.021), as well as a lower cortisol response in DUI offenders than the comparison group (F(1,39) = 5.71, p = 0.022). Finally, for recidivists, hierarchical regression analyses indicated that experience seeking (R-2 = 0.23, p = 0.008), followed by number of cigarettes smoked daily (R-Delta(2) = 0.12, p = 0.031), combined to explain 35% of the variance in cortisol (F(2,29) = 7.26, p = 0.003). These findings indicate that severe recidivism may have psychobiological underpinnings, and that HPA axis dysregulation appears to be a mechanism common to high-risk behaviours including DUI recidivism, sensation seeking, and cigarette smoking. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Couture, Sophie; Brown, Thomas G.; Ouimet, Marie Claude; Gianoulakis, Christina; Tremblay, Jacques] Douglas Hosp, Res Ctr, Addict Res Program, Verdun, PQ H4H 1R3, Canada. [Couture, Sophie] Univ Montreal, Ecole Criminol, Montreal, PQ H3C 3J7, Canada. [Brown, Thomas G.; Gianoulakis, Christina; Tremblay, Jacques] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Brown, Thomas G.] St Philippe Laprairie, Pavillon Foster Addict Treatment Program, Montreal, PQ, Canada. [Ouimet, Marie Claude] NICHHD, Natl Inst Hlth, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Carbonneau, Rene] Univ Montreal, Child Psychosocial Maladjustment Res Unt, Montreal, PQ H3C 3J7, Canada. RP Brown, TG (reprint author), Douglas Hosp, Res Ctr, Addict Res Program, 6875 LaSalle Blvd,Perry 4, Verdun, PQ H4H 1R3, Canada. EM thomas.brown@mcgill.ca NR 64 TC 8 Z9 9 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD JAN PY 2008 VL 40 IS 1 BP 246 EP 253 DI 10.1016/j.aap.2007.06.003 PG 8 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 265GG UT WOS:000253346500030 PM 18215555 ER PT J AU Ghosh, AK Chapsal, BD Weber, IT Mitsuya, H AF Ghosh, Arun K. Chapsal, Bruno D. Weber, Irene T. Mitsuya, Hiroaki TI Design of HIV protease inhibitors targeting protein backbone: An effective strategy for combating drug resistance SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID VIRUS TYPE-1 PROTEASE; ORALLY BIOAVAILABLE INHIBITOR; HIGH-AFFINITY P-2-LIGANDS; CRYSTAL-STRUCTURE; ACTIVE-SITE; IN-VITRO; POTENT; GENERATION; RESOLUTION; TMC114 AB The discovery of human immunodeficiency virus (HIV) protease inhibitors (Pls) and their utilization in highly active antiretroviral therapy (HAART) have been a major turning point in the management of HIV/acquired immune-deficiency syndrome (AIDS). However, despite the successes in disease management and the decrease of HIV/AIDS-related mortality, several drawbacks continue to hamper first-generation protease inhibitor therapies. The rapid emergence of drug resistance has become the most urgent concern because it renders current treatments ineffective and therefore compels the scientific community to continue efforts in the design of inhibitors that can efficiently combat drug resistance. The present line of research focuses on the presumption that an inhibitor that can maximize interactions in the HIV-1 protease active site, particularly with the enzyme backbone atoms, will likely retain these interactions with mutant enzymes. Our structure-based design of HIV Pls specifically targeting the protein backbone has led to exceedingly potent inhibitors with superb resistance profiles. We initially introduced new structural templates, particulary non-peptidic conformationally constrained P-2 ligands that would efficiently mimic peptide binding in the S-2 subsite of the protease and provide enhanced bioavailability to the inhibitor. Cyclic ether derived ligands appeared as privileged structural features and allowed us to obtain a series of potent Pls. Following our structure-based design approach, we developed a high-affinity 3(R),3a(R),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) ligand that maximizes hydrogen bonding and hyrophobic interactions in the protease S2 subsite. Combination of this ligand with a range of different isosteres led to a series of exceedingly potent inhibitors. Darunavir, initially TMC-114, which combines the bis-THF ligand with a sulfonamide isostere, directly resulted from this line of research. This inhibitor displayed unprecedented enzyme inhibitory potency (K-i = 16 pM) and antiviral activity (IC90 = 4.1 nM) Most importantly, it consistently retained is potency against highly drug-resistant HIV strains. Darunavir's IC50 remained in the low nanomolar range against highly mutated HIV strains that displayed resistance to most available Pls. Our detailed crystal structure analyses of darunavir-bound protease complexes clearly demonstrated extensive hydrogen bonding between the inhibitor and the protease backbone. Most strikingly, these analyses provided ample evidence of the unique contribution of the bis-THF as a P-2-ligand. With numerous hydrogen bonds, bis-THF was shown to closely and tightly bind to the backbone atoms of the S-2 subsite of the protease. Such tight interactions were consistently observed with mutant proteases and might therefore account for the unusually high resistance profile of darunavir. Optimization attempts of the backbone binding in other subsites of the enzyme, through rational modifications of the isostere or tailor made P-2 ligands, led to equally impressive inhibitors with excellent resistance profiles. The concept of targeting the protein backbone in current structure-based drug design may offer a reliable strategy for combating drug resistance. C1 [Ghosh, Arun K.] Purdue Univ, Dept Chem, Indiana, PA USA. [Ghosh, Arun K.; Chapsal, Bruno D.] Purdue Univ, Dept Med Chem, Indiana, PA USA. [Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Dept Hematol, Sch Med, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] Kumamoto Univ, Dept Infect Dis, Sch Med, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, Indiana, PA USA. EM akghosh@purdue.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM 53386, R01 GM062920, R01 GM062920-09, R01 GM062920-10] NR 42 TC 130 Z9 133 U1 0 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD JAN PY 2008 VL 41 IS 1 BP 78 EP 86 DI 10.1021/ar7001232 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 252BJ UT WOS:000252419500010 PM 17722874 ER PT J AU Rosenfeld, S AF Rosenfeld, Simon TI Approximate Bivariate Gamma Generator with Prespecified Correlation and Different Marginal Shapes SO ACM TRANSACTIONS ON MODELING AND COMPUTER SIMULATION LA English DT Article DE Bivariate gamma distribution; correlation coefficient; random sampling; dietary assessment ID DISTRIBUTIONS; VARIANCES AB A new algorithm is proposed for generating approximate bivariate gamma random samples with a prespecified correlation coefficient and different marginal shapes. A distinctive feature of this approach is computational simplicity and ease of control. Extensive testing demonstrates high accuracy of the proposed algorithm. An S-PLUS code implementing the algorithm is provided. Regression lines produced by the technique are nearly linear, even when marginal shapes are drastically different. This feature makes the approach especially useful in simulation studies associated with linear regression problems. A real-life example of application to the analysis of heteroscedastic regression models is presented. This analysis is a part of a bigger study aimed at quantification of risk factors in cancer research. Two-dimensional probabilistic patterns produced by the algorithm are compared to those generated by the well-known technique by Schmeiser and Lal [1982]. C1 NCI, Rockville, MD 20852 USA. RP Rosenfeld, S (reprint author), NCI, 6130 Execut Blvd,EPN,Room 3108, Rockville, MD 20852 USA. EM sr212a@nih.gov NR 25 TC 2 Z9 2 U1 0 U2 1 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 2 PENN PLAZA, STE 701, NEW YORK, NY 10121-0701 USA SN 1049-3301 J9 ACM T MODEL COMPUT S JI ACM Trans. Model. Comput. Simul. PY 2008 VL 18 IS 4 AR 16 DI 10.1145/1391978.1391982 PG 20 WC Computer Science, Interdisciplinary Applications; Mathematics, Applied SC Computer Science; Mathematics GA 359JF UT WOS:000259982000004 ER PT J AU Melnikov, EE Andrianova, AG Morozkin, AD Stepnov, AA Makhovskaya, OV Botos, I Gustchina, A Wlodawer, A Rotanova, TV AF Melnikov, Edward E. Andrianova, Anna G. Morozkin, Andrey D. Stepnov, Anton A. Makhovskaya, Oksana V. Botos, Istvan Gustchina, Alla Wlodawer, Alexander Rotanova, Tatyana V. TI Limited proteolysis of E. coli ATP-dependent protease Lon - a unified view of the subunit architecture and characterization of isolated enzyme fragments SO ACTA BIOCHIMICA POLONICA LA English DT Article DE AAA(+) protein; ATP-dependent proteases; Lon; Lon domains; Limited proteolysis ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; ACTIVE-SITE; CONFORMATIONAL-CHANGES; PEPTIDASE ACTIVITY; CATALYTIC DYAD; AAA PROTEINS; LA PROTEASE; DNA-BINDING; DOMAIN AB We carried out chymotryptic digestion of multimeric ATP-dependent Lon protease from Escherichia coli. Four regions sensitive to proteolytic digestion were located in the enzyme and several fragments corresponding to the individual structural domains of the enzyme or their combinations were isolated. It was shown that M unlike the known AAA(+) proteins, the ATPase fragment (A) of Lon has no ATPase activity in spite of its ability to bind nucleotides, and it is monomeric in solution regardless of the presence of any effectors; (ii) the monomeric proteolytic domain (P) does not display proteolytic activity; (iii) in contrast to the inactive counterparts, the AP fragment is an oligomer and exhibits both the ATPase and proteolytic activities. However, unlike the full-length Lon, its AP fragment oligomerizes into a dimer or a tetramer only, exhibits the properties of a non-processive protease, and undergoes self-degradation upon ATP hydrolysis. These results reveal the crucial role played by the non-catalytic N fragment of Lon (including its coiled-coil region), as well as the contribution of individual domains to creation of the quaternary structure of the full-length enzyme, empowering its function as a processive protease. C1 [Melnikov, Edward E.; Andrianova, Anna G.; Stepnov, Anton A.; Makhovskaya, Oksana V.; Rotanova, Tatyana V.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. [Morozkin, Andrey D.] Cardiol Res Ctr, Inst Expt Cardiol, Moscow 121552, Russia. [Botos, Istvan] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. [Gustchina, Alla; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Rotanova, TV (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Miklukho Maklaya 16-10,GSP-7, Moscow 117997, Russia. EM rotanova@enzyme.siobc.ras.ru FU Russian Foundation for Basic Research [05-04-48383]; US Civilian Research and Development Foundation [RB1-2505-MO-03]; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX This work was supported in part by grant 05-04-48383 from the Russian Foundation for Basic Research, by the US Civilian Research and Development Foundation grant RB1-2505-MO-03, and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 70 TC 10 Z9 12 U1 0 U2 2 PU ACTA BIOCHIMICA POLONICA PI WARSAW PA PASTEURA 3, 02-093 WARSAW, POLAND SN 0001-527X J9 ACTA BIOCHIM POL JI Acta Biochim. Pol. PY 2008 VL 55 IS 2 BP 281 EP 296 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 359EF UT WOS:000259968500007 PM 18506223 ER PT J AU Devoogdt, N Rasool, N Simpkins, F Cohen, J Tchabo, N Revets, H Ghassabeh, GH Kohn, E De Baetselier, P AF Devoogdt, Nick Rasool, Nabila Simpkins, Fiona Cohen, Joshua Tchabo, Nana Revets, Hilde Ghassabeh, Gholamreza Hassanzadeh Kohn, Elise De Baetselier, Patrick TI Secretory leukocyte protease inhibitor (SLPI) promotes cancer by preventing degradation of the growth-and survival factor progranulin (PRGN) SO ACTA CLINICA BELGICA LA English DT Meeting Abstract C1 [Devoogdt, Nick; Revets, Hilde; Ghassabeh, Gholamreza Hassanzadeh; De Baetselier, Patrick] Vrije Univ Brussels, Vlaams Interuniv Inst Voor Biotechnol, Dept Cellular & Mol Interact, Brussels, Belgium. [Rasool, Nabila; Simpkins, Fiona; Cohen, Joshua; Tchabo, Nana; Kohn, Elise] NIH, Mol Signaling Sect, Pathol Lab, NCI, Bethesda, MD 20892 USA. EM ndevoogd@vub.ac.be RI De Baetselier, Patrick/D-3866-2014; Devoogdt, Nick/H-5156-2013 OI Devoogdt, Nick/0000-0001-9220-4833 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACTA CLINICA BELGICA PI GHENT PA UNIV HOSPITAL GENT, DE PINTELAAN 185, RENAL DIVISION, B-9000 GHENT, BELGIUM SN 0001-5512 J9 ACTA CLIN BELG JI Acta Clin. Belg. PD JAN-FEB PY 2008 VL 63 IS 1 BP 48 EP 48 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 269QP UT WOS:000253664300010 ER PT J AU Pan, QJ Roth, MJ Guo, HQ Koclunan, ML Wang, GQ Henry, M Wei, WQ Giffen, CA Lu, N Abnet, CC Hao, CQ Taylor, PR Qiao, YL Dawsey, SM AF Pan, Qin-Jing Roth, Mark J. Guo, Hui-Qin Koclunan, Michael L. Wang, Guo-Qing Henry, Michael Wei, Wen-Qiang Giffen, Carol A. Lu, Ning Abnet, Christian C. Hao, Chang-Qing Taylor, Philip R. Qiao, You-Lin Dawsey, Sanford M. TI Cytologic detection of esophageal squamous cell carcinoma and its precursor lesions using balloon samplers and liquid-based cytology in asymptomatic adults in Linxian, China SO ACTA CYTOLOGICA LA English DT Article DE carcinoma; esophageal squamous cell; cytology; esophageal balloon; dysplasia; squamous; screening ID CERVICAL CYTOLOGY; POPULATION; DYSPLASIA; ACCURACY; CANCER AB Objective To evaluate liquid-based balloon cytology as primary screening tool for detecting esophageal cancer in a high-risk population. Study Design Study subjects were 940 asymptomatic subjects ages 34 - 67 in Linxian, Henan Province, China, an area with a high incidence of esophageal carcinoma. We collected esophageal samples with balloon from all subjects into a liquid buffer (AutoCyte Preservative) and made thin-layer slides for cytologic screening using AutoCyte PREP (TriPath Imaging Inc., Burlington, North Carolina, U.S.A). Subsequent endoscopic biopsies on all subjects served as the gold standard. All tests were performed in an independent and blinded fashion. We compared the results of liquid-based cytology with the results of endoscopic biopsy. Results Carcinoma in situ and cancer were identified in 17 of 710 (2.4%) subjects who had results of endoscopic biopsy and liquid-based balloon cytology. Taking atypical squamous cells of undetermined significance, favor neoplastic (ASCUS-N) as the cytologic threshold for detecting esophageal cancer, the sensitivity and the specificity of liquid-based balloon cytology were 76.5% and 76.0%, respectively. Conclusion The accuracy of liquid-based technique (AutoCyte PREP) was much better than with previous balloon smear cytology. It may he an alternative for a primary screening for esophageal and cardia stomach cancer in low-resource settings where endoscopy is not available,. C1 [Pan, Qin-Jing; Roth, Mark J.; Guo, Hui-Qin; Koclunan, Michael L.; Wang, Guo-Qing; Henry, Michael; Wei, Wen-Qiang; Giffen, Carol A.; Lu, Ning; Abnet, Christian C.; Hao, Chang-Qing; Taylor, Philip R.; Qiao, You-Lin; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. [Pan, Qin-Jing; Roth, Mark J.; Guo, Hui-Qin; Koclunan, Michael L.; Wang, Guo-Qing; Henry, Michael; Wei, Wen-Qiang; Giffen, Carol A.; Lu, Ning; Abnet, Christian C.; Hao, Chang-Qing; Taylor, Philip R.; Qiao, You-Lin; Dawsey, Sanford M.] Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing, Peoples R China. [Pan, Qin-Jing; Roth, Mark J.; Guo, Hui-Qin; Koclunan, Michael L.; Wang, Guo-Qing; Henry, Michael; Wei, Wen-Qiang; Giffen, Carol A.; Lu, Ning; Abnet, Christian C.; Hao, Chang-Qing; Taylor, Philip R.; Qiao, You-Lin; Dawsey, Sanford M.] Chinese Acad Med Sci, Inst Canc, Dept Endoscopy, Beijing, Peoples R China. [Pan, Qin-Jing; Roth, Mark J.; Guo, Hui-Qin; Koclunan, Michael L.; Wang, Guo-Qing; Henry, Michael; Wei, Wen-Qiang; Giffen, Carol A.; Lu, Ning; Abnet, Christian C.; Hao, Chang-Qing; Taylor, Philip R.; Qiao, You-Lin; Dawsey, Sanford M.] Chinese Acad Med Sci, Inst Canc, Dept Cytol, Beijing, Peoples R China. [Pan, Qin-Jing; Roth, Mark J.; Guo, Hui-Qin; Koclunan, Michael L.; Wang, Guo-Qing; Henry, Michael; Wei, Wen-Qiang; Giffen, Carol A.; Lu, Ning; Abnet, Christian C.; Hao, Chang-Qing; Taylor, Philip R.; Qiao, You-Lin; Dawsey, Sanford M.] Chinese Acad Med Sci, Inst Canc, Dept Pathol, Beijing, Peoples R China. [Pan, Qin-Jing; Roth, Mark J.; Guo, Hui-Qin; Koclunan, Michael L.; Wang, Guo-Qing; Henry, Michael; Wei, Wen-Qiang; Giffen, Carol A.; Lu, Ning; Abnet, Christian C.; Hao, Chang-Qing; Taylor, Philip R.; Qiao, You-Lin; Dawsey, Sanford M.] Univ Penn, Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Pan, Qin-Jing; Roth, Mark J.; Guo, Hui-Qin; Koclunan, Michael L.; Wang, Guo-Qing; Henry, Michael; Wei, Wen-Qiang; Giffen, Carol A.; Lu, Ning; Abnet, Christian C.; Hao, Chang-Qing; Taylor, Philip R.; Qiao, You-Lin; Dawsey, Sanford M.] Univ Maryland, Dept Cytol, Baltimore, MD 21201 USA. [Pan, Qin-Jing; Roth, Mark J.; Guo, Hui-Qin; Koclunan, Michael L.; Wang, Guo-Qing; Henry, Michael; Wei, Wen-Qiang; Giffen, Carol A.; Lu, Ning; Abnet, Christian C.; Hao, Chang-Qing; Taylor, Philip R.; Qiao, You-Lin; Dawsey, Sanford M.] Informat Management Serv Inc, Silver Spring, MD USA. [Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Roth, MJ (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 6120 Execut Blvd,Suite 320,MSC 7232, Bethesda, MD 20892 USA. EM mr166i@nih.gov RI Qiao, You-Lin/B-4139-2012; OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU Intramural NIH HHS; NCI NIH HHS [N01-SC-91019] NR 14 TC 28 Z9 29 U1 0 U2 4 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JAN-FEB PY 2008 VL 52 IS 1 BP 14 EP 23 DI 10.1159/000325430 PG 10 WC Pathology SC Pathology GA 256JC UT WOS:000252723600003 PM 18323271 ER PT J AU Huter, E Wortham, NC Hartschub, W Enk, A Jappe, U AF Huter, Eva Wortham, Noel C. Hartschub, Wolfgang Enk, Alexander Jappe, Uta TI Single base mutation in the fumarate hydratase gene leading to segmental cutaneous Leiomyomatosis SO ACTA DERMATO-VENEREOLOGICA LA English DT Letter ID RENAL-CELL CANCER; HEREDITARY LEIOMYOMATOSIS; UTERINE LEIOMYOMATOSIS; FH MUTATIONS; MULTIPLE; ZOSTERIFORM; FIBROIDS C1 [Huter, Eva; Hartschub, Wolfgang; Enk, Alexander; Jappe, Uta] Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany. [Wortham, Noel C.] Canc Res UK, Mol & Populat Genet Lab, London, England. RP Huter, E (reprint author), NIH, NIAID, Immunol Lab, Bethesda, MD 20892 USA. EM hutere@niaid.nih.gov NR 17 TC 6 Z9 7 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2008 VL 88 IS 1 BP 63 EP 65 DI 10.2340/00015555-0341 PG 3 WC Dermatology SC Dermatology GA 260CC UT WOS:000252987400016 PM 18176756 ER PT J AU Liu, XD Sun, LG Yin, XB Wang, YH AF Liu Xiaodong Sun Liguang Yin Xuebin Wang Yuhong TI Heavy Metal Distributions and Source Tracing in the Lacustrine Sediments of Dongdao Island, South China Sea SO ACTA GEOLOGICA SINICA-ENGLISH EDITION LA English DT Article DE heavy metals; elemental geochemistry; ornithogenic sediments; Dongdao Island; South China Sea ID PEARL RIVER ESTUARY; KING-GEORGE-ISLAND; LAKE-SEDIMENTS; GEOCHEMICAL EVIDENCE; LEAD CONTAMINATION; PENGUIN DROPPINGS; PELAGIC SEDIMENTS; URBAN-ENVIRONMENT; POLLUTION; MERCURY AB The levels and depth distributions of As, Cd, Cu, Zn, Pb, Hg, Fe and Mn in two sediment cores DY2 and DY4 collected from the "Cattle Pond" of Dongdao Island, South China Sea, were determined and analyzed with the main objective to identify the sources of these elements and evaluate the corresponding sedimentological and geochemical processes. Lithological characters and sedimentary parameters such as LOI(95 degrees C), CaO, LOI(550 degrees C) and TOC indicate that the depth of 96 cm and 87 cm are the critical points for DY2 and DY4 cores, respectively. As, Cd, Cu, Zn, Hg and P are remarkably enriched in the ornithogenic sediments above the critical depth points; their concentration-versus-depth profiles are similar to those of TOC and LOI(550 degrees C) the ratios of As, Cd, Cu, Zn, Hg over Ca are significantly correlated with P/Ca. Statistical and comparative analyses of these elements' levels in the ornithogenic sediments of DY2 and DY4 strongly suggest that seabird droppings are the main source of these elements. Additionally, for the upper sediment layers of DY2 and DY4 cores, Fe oxide sorption mechanism, like organic matter, may also play an important role in the abundances of heavy metals. Heavy metal Pb has geochemical characteristics distinctly different from those of As, Cd, Cu, Zn, Hg and P, and its isotope composition indicates an origin of anthropogenic emissions from the surrounding countries. These geochemical characteristics in the orinithogenic sediments of Xisha Islands are compared with the studies in the remote Antarctic and Arctic regions. C1 [Liu Xiaodong; Sun Liguang; Yin Xuebin] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. [Wang Yuhong] NIH, Bethesda, MD 20892 USA. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. EM slg@ustc.edu.cn NR 54 TC 7 Z9 7 U1 2 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1000-9515 J9 ACTA GEOL SIN-ENGL JI Acta Geol. Sin.-Engl. Ed. PY 2008 VL 82 IS 5 SI 4 BP 1002 EP 1014 PG 13 WC Geosciences, Multidisciplinary SC Geology GA V10QW UT WOS:000207479500009 ER PT J AU Karmaliani, R Irfan, F Bann, C Mcclure, E Moss, N Pasha, O Goldenberg, R AF Karmaliani, Rozina Irfan, Farhana Bann, Carla M. Mcclure, Elizabeth M. Moss, Nancy Pasha, Omrana Goldenberg, Robert L. TI Domestic violence prior to and during pregnancy among Pakistani women SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE Domestic violence; Pakistan; physical abuse ID INTIMATE PARTNER VIOLENCE; MULTICOUNTRY; PREVALENCE; HEALTH; ABUSE; INDIA AB Objective. Abuse of women has been associated with adverse pregnancy outcomes. Data about abuse from developing countries are scarce, especially from Muslim societies. Our objective was to investigate domestic violence before and during pregnancy among women in an urban area of Pakistan. Design. Population-based cohort study. Setting. An urban community in Hyderabad, Pakistan. Population. Thousand three hundred and twenty-four pregnant women at 20-26 weeks gestation. Methods. Socio-demographic and reproductive history data were obtained through structured interviews. We used a modified World Health Organization screening instrument to assess women's experience of domestic violence. Measures. Physical, sexual, and verbal abuse and demographic characteristics. Results. The majority of women had received some schooling and in most households the husbands were employed; by Pakistani standards, they were middle class. Young maternal age, having an unemployed husband and one with other wives/partners, and having had a prior pregnancy were significant predictors of abuse. In the six months prior to and/or during pregnancy, 51% reported experiencing verbal, physical or sexual abuse. Twenty percent reported physical or sexual abuse alone. Sixteen percent of women considered suicide as a response to the abuse. Conclusions. Domestic violence is common among urban Pakistani women of reproductive age, suggesting a need for universal screening during antenatal care, and for support and referral. Further research is needed to determine factors that place women at greatest risk, and to assess the impact of domestic violence on pregnancy outcomes. C1 [Bann, Carla M.; Mcclure, Elizabeth M.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Karmaliani, Rozina; Irfan, Farhana; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan. [Moss, Nancy] NICHD, Rockville, MD USA. [Goldenberg, Robert L.] Drexel Univ, Philadelphia, PA 19104 USA. RP Mcclure, E (reprint author), Res Triangle Inst, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA. EM mcclure@rti.org FU National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research and the Bill and Melinda Gates Foundation [uol HD 40636, uol HD 40607] FX This study was funded through grants from the National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research and the Bill and Melinda Gates Foundation. (uol HD 40636, uol HD 40607). NR 31 TC 18 Z9 18 U1 0 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 2008 VL 87 IS 11 BP 1194 EP 1201 DI 10.1080/00016340802460263 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 374BJ UT WOS:000261017000016 PM 18951219 ER PT J AU Aragon-Ching, JB Ning, YM Dahut, WL AF Aragon-Ching, Jeanny B. Ning, Yang-Min Dahut, William L. TI Acute aortic dissection in a hypertensive patient with prostate cancer undergoing chemotherapy containing bevacizumab SO ACTA ONCOLOGICA LA English DT Editorial Material C1 [Aragon-Ching, Jeanny B.; Ning, Yang-Min; Dahut, William L.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Dahut, WL (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov OI Aragon-Ching, Jeanny/0000-0002-6714-141X FU Intramural NIH HHS NR 6 TC 7 Z9 7 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 2008 VL 47 IS 8 BP 1600 EP 1601 DI 10.1080/02841860801978905 PG 2 WC Oncology SC Oncology GA 362WK UT WOS:000260227700022 PM 18607842 ER PT B AU Guettier, JM Gorden, P AF Guettier, Jean-Marc Gorden, Phillip BE VandenBerghe, G TI Hypoglycemia: An Endocrine Emergency SO ACUTE ENDOCRINOLOGY: FROM CAUSE TO CONSEQUENCE SE Contemporary Endocrinology LA English DT Article; Book Chapter ID GROWTH-HORMONE DEFICIENCY; NONINSULINOMA PANCREATOGENOUS HYPOGLYCEMIA; PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA; ETHANOL-INDUCED HYPOGLYCEMIA; INSULIN-INDUCED HYPOGLYCEMIA; SURGICALLY TREATED PATIENTS; GASTRIC-BYPASS-SURGERY; ISLET-CELL TUMOR; REACTIVE HYPOGLYCEMIA; FACTOR-II C1 [Guettier, Jean-Marc; Gorden, Phillip] NIDDK, NIH, Bethesda, MD 20892 USA. RP Guettier, JM (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. NR 102 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 BN 978-1-60327-176-9 J9 CONTEMP ENDOCRINOL S PY 2008 BP 149 EP 164 DI 10.1007/978-1-60327-177-6_7 D2 10.1007/978-1-60327-177-6 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BJO76 UT WOS:000266909700007 ER PT S AU Uhl, GR Drgon, T Johnson, C Li, CY Contoreggi, C Hess, J Naiman, D Liu, QR AF Uhl, George R. s Drgon, Tomas Johnson, Catherine Li, Chuan-Yun Contoreggi, Carlo Hess, Judith Naiman, Daniel Liu, Qing-Rong BE Uhl, GR TI Molecular Genetics of Addiction and Related Heritable Phenotypes Genome-Wide Association Approaches Identify "Connectivity Constellation" and Drug Target Genes with Pleiotropic Effects SO ADDICTION REVIEWS 2008 SE Annals of the New York Academy of Sciences LA English DT Article DE pleiotropic; cell adhesion; Monte Carlo ID PROTEIN-TYROSINE-PHOSPHATASE; SINGLE-NUCLEOTIDE POLYMORPHISMS; MICE LACKING FIBROBLAST-GROWTH-FACTOR-14; ALDEHYDE DEHYDROGENASE GENOTYPES; ALCOHOL-METABOLIZING GENES; CELL-ADHESION MOLECULES; POPULATION-BASED SAMPLE; LONG-TERM POTENTIATION; MILD MENTAL IMPAIRMENT; RECEPTOR SUBUNIT GENES AB Genome-wide association (GWA) can elucidate molecular genetic bases for human individual differences in complex phenotypes that include vulnerability to addiction. Here, we review (a) evidence that supports polygenic models with (at least) modest heterogeneity for the genetic architectures of addiction and several related phenotypes; (b) technical and ethical aspects of importance for understanding GWA data, including genotyping in individual samples versus DNA pools, analytic approaches, power estimation, and ethical issues in genotyping individuals with illegal behaviors; (c) the samples and the data that shape our current understanding of the molecular genetics of individual differences in vulnerability to substance dependence and related phenotypes; (d) overlaps between GWA data sets for dependence on different substances; and (e) overlaps between GWA data for addictions versus other heritable, brain-based phenotypes that include bipolar disorder, cognitive ability, frontal lobe brain volume, the ability to successfully quit smoking, neuroticism, and Alzheimer's disease. These convergent results identify potential targets for drugs that might modify addictions and play roles in these other phenotypes. They add to evidence that individual differences in the quality and quantity of brain connections make pleiotropic contributions to individual differences in vulnerability to addictions and to related brain disorders and phenotypes. A "connectivity constellation" of brain phenotypes and disorders appears to receive substantial pathogenic contributions from individual differences in a constellation of genes whose variants provide individual differences in the specification of brain connectivities during development and in adulthood. Heritable brain differences that underlie addiction vulnerability thus lie squarely in the midst of the repertoire of heritable brain differences that underlie vulnerability to other common brain disorders and phenotypes. C1 [Uhl, George R. s; Drgon, Tomas; Johnson, Catherine; Li, Chuan-Yun; Liu, Qing-Rong] Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Intramural Res Program, Baltimore, MD USA. [Li, Chuan-Yun] Peking Univ, Ctr Bioinformat, Coll Life Sci, Beijing 100871, Peoples R China. [Contoreggi, Carlo; Hess, Judith] NIDA, Off Clin Director, NIH, IRP, Baltimore, MD USA. [Naiman, Daniel] Johns Hopkins Univ, Dept Math, Baltimore, MD 21218 USA. RP Uhl, GR (reprint author), Box 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Naiman, Daniel/A-3304-2010; Liu, Qing-Rong/A-3059-2012 OI Naiman, Daniel/0000-0001-6504-9081; Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS [Z01 DA000165-12, Z01 DA000401-10, Z01 DA000492-03, Z01 DA000537-02]; NCI NIH HHS [P50 CA/DA84718, P50 CA084719, P50 CA84719, R01 CA063562, R01 CA63562]; NHLBI NIH HHS [HL32318, HL51429]; NICHD NIH HHS [N01 HD13138]; NIDA NIH HHS [1K08 DA14276-05, DA08511, K08 DA014276]; Wellcome Trust [076113] NR 301 TC 69 Z9 69 U1 2 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-727-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1141 BP 318 EP 381 DI 10.1196/annals.1441.018 PG 64 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BIM56 UT WOS:000260859100018 PM 18991966 ER PT J AU Cranford, JA McCabe, SE Boyd, CJ Slayden, J Reed, MB Ketchie, JM Lange, JE Scott, MS AF Cranford, James A. McCabe, Sean Esteban Boyd, Carol J. Slayden, Janie Reed, Mark B. Ketchie, Julie M. Lange, James E. Scott, Marcia S. TI Reasons for nonresponse in a web-based survey of alcohol involvement among first-year college students SO ADDICTIVE BEHAVIORS LA English DT Article DE reasons for nonresponse; Web surveys; college students; heavy episodic drinking AB This study conducted a follow-up telephone survey of a probability sample of college students who did not respond to a Web survey to determine correlates of and reasons for nonresponse. A stratified random sample of 2502 full-time first-year undergraduate students was invited to participate in a Web-based survey. A random sample of 221 students who did not respond to the original Web survey completed an abbreviated version of the original survey by telephone. Nonresponse did not vary by gender, but nonresponse was higher among Blacks and Hispanics compared to Whites, and Blacks compared to Asians. Nonresponders reported lower frequency of past 28 days drinking, lower levels of past-year and past 28-days heavy episodic drinking, and more time spent preparing for classes than responders. The most common reasons for nonresponse were "too busy" (45.7%), "not interested" (18.1%), and "forgot to complete survey" (18.1 %). Reasons for nonresponse to Web surveys among college students are similar to reasons for nonresponse to mail and telephone surveys, and some nonresponse reasons vary as a function of alcohol involvement. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Cranford, James A.; McCabe, Sean Esteban; Boyd, Carol J.; Slayden, Janie] Univ Michigan, Subst Abuse Res Ctr, Ann Arbor, MI 48105 USA. [Reed, Mark B.; Ketchie, Julie M.; Lange, James E.] San Diego State Univ, Res Fdn, AOD Initiat Res, San Diego, CA 92120 USA. [Scott, Marcia S.] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. RP Cranford, JA (reprint author), Univ Michigan, Subst Abuse Res Ctr, 2025 Traverwood Dr,Suite C, Ann Arbor, MI 48105 USA. EM jcranfor@med.umich.edu RI Croff, Julie/I-6861-2012; OI McCabe, Sean/0000-0002-9622-4652 FU NIAAA NIH HHS [U18 AA015275, U18 AA015275-03] NR 10 TC 27 Z9 27 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JAN PY 2008 VL 33 IS 1 BP 206 EP 210 DI 10.1016/j.addbeh.2007.07.008 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 265WD UT WOS:000253391600022 PM 17728069 ER PT J AU Montoya, ID AF Montoya, Ivan D. TI Immunotherapies for drug addictions SO ADICCIONES LA Spanish DT Editorial Material DE immunotherapy vaccine; drug abuse; treatment; cocaine; nicotine ID NICOTINE CONJUGATE VACCINE; DEPENDENCE; BRAIN; ABUSE AB Immunotherapies in the form of vaccines (active immunization) or monoclonal antibodies (passive immunization) appear safe and a promising treatment approaches for some substance-related disorders. The mechanism of action of the antibody therapy is by preventing the rapid entry of drugs of abuse into the central nervous system. In theory, immunotherapies could have several clinical applications. Monoclonal antibodies may be useful to treat drug overdoses and prevent the neurotoxic effects of drugs by blocking the access of drugs to the brain. Vaccines may help to prevent the development of addiction, initiate drug abstinence in those already addicted to drugs, or prevent drug use relapse by reducing the pharmacological effects and rewarding properties of the drugs of abuse on the brain. Passive immunization with monoclonal antibodies has been investigated for cocaine, methamphetamine, nicotine, and phencyclidine (PCP). Active immunization with vaccines has been studied for cocaine, heroin, methamphetamine, and nicotine. These immunotherapies seem promising therapeutic tools and are at different stages in their development before they can be approved by regulatory agencies for the treatment of substance-related disorders. The purpose of this article is to review the current immunotherapy approaches with emphasis on the risks and benefits for the treatment of these disorders. C1 Natl Inst Drug Abuse, Bethesda, MD USA. RP Montoya, ID (reprint author), Natl Inst Drug Abuse, Bethesda, MD USA. EM imontoya@mail.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 15 TC 2 Z9 4 U1 0 U2 1 PU SOCIDROGALCOHOL PI PALMA DE MALLORCA PA RAMBLA 15, 2A, 3A,, PALMA DE MALLORCA, BALEARES 07003, SPAIN SN 0214-4840 J9 ADICCIONES JI Adicciones PY 2008 VL 20 IS 2 BP 111 EP 115 PG 5 WC Substance Abuse SC Substance Abuse GA 335VK UT WOS:000258320000002 PM 18551223 ER PT J AU Monk, CS Pine, DS AF Monk, Christopher S. Pine, Daniel S. BE Allen, NB Sheeber, LB TI Cognitive factors in depressive disorders: a developmental perspective SO ADOLESCENT EMOTIONAL DEVELOPMENT AND THE EMERGENCE OF DEPRESSIVE DISORDERS LA English DT Article; Book Chapter ID GENERALIZED ANXIETY DISORDER; PEDIATRIC BIPOLAR DISORDER; THREATENING FACIAL EXPRESSIONS; MAJOR DEPRESSION; EMOTIONAL INFORMATION; ATTENTIONAL BIAS; DECISION-MAKING; ANTIDEPRESSANT TREATMENT; CONSTRUCT ACCESSIBILITY; LEARNED HELPLESSNESS C1 [Monk, Christopher S.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. RP Monk, CS (reprint author), Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. RI Monk, Christopher/J-1805-2014 NR 73 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-86939-3 PY 2008 BP 156 EP 173 DI 10.1017/CBO9780511551963.009 D2 10.1017/CBO9780511551963 PG 18 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA BBC15 UT WOS:000306419600009 ER PT S AU Greig, NH Utsuki, T Yu, QS Holloway, HW Perry, T Tweedie, D Giordano, T Alley, GM Chen, DM Kamal, MA Rogers, JT Sambamurti, K Lahiri, DK AF Greig, Nigel H. Utsuki, Tada Yu, Qian-sheng Holloway, Harold W. Perry, Tracyann Tweedie, David Giordano, Tony Alley, George M. Chen, De-Mao Kamal, Mohammad A. Rogers, Jack T. Sambamurti, Kumar Lahiri, Debomoy K. BE Fisher, A Memo, M Stocchi, F Hanin, I TI Dissociation between the potent beta-amyloid protein pathway inhibition and cholinergic actions of the Alzheimer drug candidates phenserine and cymserine SO ADVANCES IN ALZHEIMER'S AND PARKINSON'S DISEASE: INSIGHTS, PROGRESS, AND PERSPECTIVES SE Advances in Behavioral Biology LA English DT Proceedings Paper CT 7th International Conference on Progress in Alzheimers and Parkinsons Disease CY MAR 09-13, 2005 CL Sorrento, ITALY ID IRON-RESPONSIVE ELEMENT; PRECURSOR PROTEIN; 5'-UNTRANSLATED REGION; RECEPTOR AGONISTS; MESSENGER-RNA; RISK-FACTORS; IN-VITRO; DISEASE; ACETYLCHOLINESTERASE; BUTYRYLCHOLINESTERASE C1 [Greig, Nigel H.; Utsuki, Tada; Yu, Qian-sheng; Holloway, Harold W.; Perry, Tracyann; Tweedie, David; Giordano, Tony; Alley, George M.; Chen, De-Mao; Kamal, Mohammad A.; Rogers, Jack T.; Sambamurti, Kumar; Lahiri, Debomoy K.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RI Kamal, Mohammad/H-9643-2012; Kamal, Mohammad/J-4622-2013; OI Kamal, Mohammad/0000-0003-1862-173X; Kamal, Mohammad Amjad/0000-0003-0088-0565 FU Intramural Research Program of the National Institute on Aging; Axonyx, Inc; Alzheimer's Association; National Institutes of Health FX We are sincerely thankful to Arnold Brossi for intellectual input. This work was supported in part by the Intramural Research Program of the National Institute on Aging (N.G., T.U., Q.Y., H.H.) and grants from Axonyx, Inc, the Alzheimers Association, and the National Institutes of Health (K.S., J.R., D.L.). NR 63 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0099-9962 BN 978-0-387-72074-6 J9 ADV BEHAV BIOL JI Adv. Behav. Biol. PY 2008 VL 57 BP 445 EP + DI 10.1007/978-0-387-72076-0_47 PG 5 WC Behavioral Sciences; Geriatrics & Gerontology; Medicine, Research & Experimental; Clinical Neurology; Neurosciences; Psychiatry SC Behavioral Sciences; Geriatrics & Gerontology; Research & Experimental Medicine; Neurosciences & Neurology; Psychiatry GA BHQ47 UT WOS:000255426400047 ER PT S AU Ha, VL Luo, RB Nie, ZZ Randazzo, PA AF Ha, Vi Luan Luo, Ruibai Nie, Zhongzhen Randazzo, Paul A. BE VandeWoude, GF Klein, G TI Contribution of AZAP-Type Arf GAPs to Cancer Cell Migration and Invasion SO ADVANCES IN CANCER RESEARCH, VOL 101 SE Advances in Cancer Research LA English DT Review; Book Chapter ID GTPASE-ACTIVATING-PROTEIN; ADP-RIBOSYLATION FACTOR; ROUS-SARCOMA VIRUS; ACTIN CYTOSKELETON; RHO-GTPASES; PHOSPHOLIPASE-D; BINDING-PROTEIN; FOCAL ADHESIONS; GOLGI-COMPLEX; PIKE GTPASE AB Arf GAPs are a family of proteins with a common catalytic domain that induces hydrolysis of GTP bound to the small GTP-binding protein Arf. The proteins arc otherwise structurally diverse. Several subtypes of Arf GAPs have been found to be targets of oncogenes and to control cell proliferation and cell migration. The latter effects are thought to be mediated by coordinating changes in actin remodeling and membrane traffic. In this chapter, we discuss Arf GAPs that have been linked to oncogenesis and the molecular mechanisms underlying the effects of these proteins in cancer cells. We also discuss the enzymology of the Arf GAPs related to possible targeted inhibition of specific subtypes of Arf GAPs. (c) 2008 Elsevier Inc. C1 [Ha, Vi Luan; Luo, Ruibai; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Nie, Zhongzhen] Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA. RP Ha, VL (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. FU National Cancer Institute; National Institutes of Health; Department of Health and Human Services FX This work was supported by the intramural program at the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 128 TC 7 Z9 7 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-374359-6 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2008 VL 101 BP 1 EP + DI 10.1016/S0065-230X(08)00401-6 PG 30 WC Oncology SC Oncology GA BIO91 UT WOS:000261403100001 PM 19055940 ER PT S AU Terabe, M Berzofsky, JA AF Terabe, Masaki Berzofsky, Jay A. BE VandeWoude, GF Klein, G TI The Role of NKT Cells in Tumor Immunity SO ADVANCES IN CANCER RESEARCH, VOL 101 SE Advances in Cancer Research LA English DT Review; Book Chapter ID KILLER-T-CELLS; LIGAND ALPHA-GALACTOSYLCERAMIDE; GROWTH-FACTOR-BETA; NONOBESE DIABETIC MICE; VERSUS-HOST-DISEASE; TRIGLYCERIDE TRANSFER PROTEIN; ANTIGEN-PRESENTING CELLS; REED-STERNBERG CELLS; COLONY-STIMULATING FACTOR; MYELOID SUPPRESSOR-CELLS AB NKT cells are a relatively newly recognized member of the immune community, with profound effects on the rest of the immune system despite their small numbers. They are trite T cells with a T cell receptor (TCR), but unlike conventional T cells that detect peptide antigens presented by conventional major histocompatibility (MHC) molecules, NKT cells recognize lipid antigens presented by CD1d, a nonclassical MHC molecule. As members of both the innate and adaptive immune systems, they. bridge the gap between these, and respond rapidly to set the tone for subsequent immune responses. They fill a unique niche in providing the immune system a cellular arm to recognize lipid antigens. They play both effector and regulatory roles in infectious, and autoimmune diseases. Furthermore, subsets of NKT cells can plan distinct and sometimes opposing roles. In cancer, type I NKT cells, defined by their invariant TCR using mice and V alpha 14J alpha 18 in mice and V alpha 14J alpha 18 in humans, are mostly protective, by producing, interferon-gamma to activate NK and CD(8+) T cells and by activating dendritic cells to make IL-12. In contrast, type II NKT cells, characterized by more diverse TCAs recognizing lipids presented by, CD1d, primarily inhibit tumor immunity. Moreover, type I and type II NKT cells counter-regulate each other forming a new immunoregulatory axis. Because NKT cells respond rapidly the balance along this axis call greatly influence other immune responses that follow. Therefore, learning to manipulate the balance along the NKT regulatory axis may be critical to devising successful immunotherapies for cancer. (c) 2008 Elsevier Inc. C1 [Terabe, Masaki; Berzofsky, Jay A.] NCI, NIH, Ctr Canc Res, Vaccine Branch, Bethesda, MD 20892 USA. RP Terabe, M (reprint author), NCI, NIH, Ctr Canc Res, Vaccine Branch, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 341 TC 142 Z9 150 U1 1 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 978-0-12-374359-6 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2008 VL 101 BP 277 EP + DI 10.1016/S0065-230X(08)00408-9 PG 75 WC Oncology SC Oncology GA BIO91 UT WOS:000261403100008 PM 19055947 ER PT B AU Richmond, BJ LaCamera, G Lerchner, A Minamimoto, T AF Richmond, Barry J. LaCamera, Giancarlo Lerchner, Alex Minamimoto, Takafumi BE Wang, R Gu, F Shen, E TI When Is It Worth Working: Calculating the Motivational Value of Working SO ADVANCES IN COGNITIVE NEURODYNAMICS, PROCEEDINGS LA English DT Proceedings Paper CT 1st International Conference on Cognitive Neurodynamics CY NOV 17-21, 2007 CL Shanghai, PEOPLES R CHINA SP E China Univ Sci & Technol, Shanghai Soc Biophys, Editorial Board Cognit Neurodynam, Natl Nat Sci Fdn China, Shangai Assoc Sci & Technol, Beijing Univ Technol, Beijing Univ Aeronaut & Astronaut, Brain Sci Res Ctr, KAIST, CAS MPG Partner Inst Computat Biol, Chinese Soc Neurosci, Chinese Soc Theoret & Appl Mech, IEEE Singapore Computat Intelligence Chapter, Int Neural Network Soc, Japanese Neural Network Soc, Nanjing Univ Aeronaut & Astronaut, Fudan Univ, Res Ctr Brain Sci, RIKEN Brain Sci Nonlinear Sci, Shanghai Univ, Shanghai Soc Nonlinar Sci, Tongji Univ, Xian Jiaotong Univ, Zhejiang Univ ID REWARD SCHEDULES; NEURONAL SIGNALS; CORTEX AB To determine what factors influence motivated behavior, we have worked to identify behavioral and neurophysiological correlates related to motivation. In these studies we have used behavioral paradigms in which monkeys must carry ou one or more simple operant behavioral trials, detecting when a visual target changes from red-green, which when done correctly, allows that monkey to either move to another identical trial or obtain a reward. Visual cues appearing at the beginning of the trials indicate whether a trial will be rewarded, or not. Monkeys react to these Cues, with the number of errors related to how long in the future the reward will be, but also contingent on how much work has been already completed. The perfonnance, both overall, and dynamical can be nicely modeled with simple modifications of ternporal difference learning models. C1 [Richmond, Barry J.; LaCamera, Giancarlo; Lerchner, Alex; Minamimoto, Takafumi] NIMH, Sect Neural Coding & Computat, Neuropsychol Lab, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Sect Neural Coding & Computat, Neuropsychol Lab, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov NR 10 TC 0 Z9 0 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4020-8386-0 PY 2008 BP 323 EP + DI 10.1007/978-1-4020-8387-7_57 PG 2 WC Neurosciences SC Neurosciences & Neurology GA BIR74 UT WOS:000262360700057 ER PT B AU Sokoloff, L AF Sokoloff, Louis BE Wang, R Gu, F Shen, E TI The Physiological and Biochemical Bases of Functional Brain Imaging SO ADVANCES IN COGNITIVE NEURODYNAMICS, PROCEEDINGS LA English DT Proceedings Paper CT 1st International Conference on Cognitive Neurodynamics CY NOV 17-21, 2007 CL Shanghai, PEOPLES R CHINA SP E China Univ Sci & Technol, Shanghai Soc Biophys, Editorial Board Cognit Neurodynam, Natl Nat Sci Fdn China, Shangai Assoc Sci & Technol, Beijing Univ Technol, Beijing Univ Aeronaut & Astronaut, Brain Sci Res Ctr, KAIST, CAS-MPG Partner Inst Computat Biol, Chinese Soc Neurosci, Chinese Soc Theoret & Appl Mech, IEEE Singapore Computat Intelligence Chapter, Int Neural Network Soc, Japanese Neural Network Soc, Nanjing Univ Aeronaut & Astronaut, Fudan Univ, Res Ctr Brain Sci, RIKEN Brain Sci Nonlinear Sci, Shanghai Univ, Shanghai Soc Nonlinar Sci, Tongji Univ, Xi an Jiaotong Univ, Zhejiang Univ ID CEREBRAL GLUCOSE-UTILIZATION; SENSORY STIMULATION; ELECTRICAL-STIMULATION; ENERGY-METABOLISM; GLUTAMATE UPTAKE; BLOOD-FLOW; RAT; ACTIVATION; DEOXYGLUCOSE; CONSUMPTION C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, NIH, Bldg 49,Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. EM louissokoloff@mail.nih.gov NR 27 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 BN 978-1-4020-8386-0 PY 2008 BP 327 EP 334 DI 10.1007/978-1-4020-8387-7_58 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BIR74 UT WOS:000262360700058 ER PT S AU Orr, N Chanock, S AF Orr, Nick Chanock, Stephen BE Hall, JC TI Common Genetic Variation and Human Disease SO ADVANCES IN GENETICS, VOL 62 SE Advances in Genetics LA English DT Review; Book Chapter ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; LYMPHOID TYROSINE PHOSPHATASE; FACTOR-H POLYMORPHISM; LINKAGE DISEQUILIBRIUM; PROSTATE-CANCER; LARGE-SCALE; POPULATION STRATIFICATION; MACULAR DEGENERATION; MYOCARDIAL-INFARCTION AB The landscape of human genetics has changed remarkably in a relatively short space of time. The field has progressed from comparatively small studies of rare genetic diseases to vast consortia based efforts that target the inherited components of common complex diseases and which typically involve thousands of individual samples. In particular, genome wide association studies have become possible as a result of a new generation of genotyping platforms. At the time of writing, these have led to the discovery of more than 150 novel susceptibility loci across a broad spectrum of diseases, a few in genes with high biological plausibility but the majority in others that had not been considered candidates. Here, we provide an overview of the field of complex disease genetics pertaining to mapping by association and consider the many pitfalls and caveats that have arisen. (C) 2008, Elsevier Inc. C1 [Orr, Nick; Chanock, Stephen] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chanock, Stephen] NCI, Core Genotyping Facil, Adv Technol Ctr, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA. RP Orr, N (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 159 TC 27 Z9 27 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 0065-2660 BN 978-0-12-374443-2 J9 ADV GENET JI Adv. Genet. PY 2008 VL 62 BP 1 EP 32 DI 10.1016/S0065-2660(08)00601-9 PG 32 WC Genetics & Heredity SC Genetics & Heredity GA BQB46 UT WOS:000280569200001 PM 19010252 ER PT S AU Govindaraju, DR Cupples, LA Kannel, WB O'Donnell, CJ Atwood, LD D'Agostino, RB Fox, CS Larson, M Levy, D Murabito, J Vasan, RS Splansky, GL Wolf, PA Benjamin, EJ AF Govindaraju, Diddahally R. Cupples, L. Adrienne Kannel, William B. O'Donnell, Christopher J. Atwood, Larry D. D'Agostino, Ralph B., Sr. Fox, Caroline S. Larson, Marty Levy, Daniel Murabito, Joanne Vasan, Ramachandran S. Splansky, Greta Lee Wolf, Philip A. Benjamin, Emelia J. BE Hall, JC TI Genetics of the Framingham Heart Study Population SO ADVANCES IN GENETICS, VOL 62 SE Advances in Genetics LA English DT Review; Book Chapter ID GENOME-WIDE LINKAGE; INDEPENDENT RISK FACTOR; FRAGMENT-LENGTH-POLYMORPHISMS; LEFT-VENTRICULAR HYPERTROPHY; CORONARY-ARTERY DISEASE; QUANTITATIVE TRAIT LOCI; BONE-MINERAL DENSITY; FOLLOW-UP EXPERIENCE; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE AB This chapter provides an introduction to the Framingham Heart Study and the genetic research related to cardiovascular diseases conducted in this unique population. It briefly describes the origins of the study, the risk factors that contribute to heart disease, and the approaches taken to discover the genetic basis of some of these risk factors. The genetic architecture of several biological risk factors has been explained using family studies, segregation analysis, heritability, and phenotypic and genetic correlations. Many quantitative trait loci underlying cardiovascular diseases have been discovered using different molecular markers. Additionally, initial results from genome-wide association studies using 116,000 markers and the prospects of using 550,000 markers for association studies are presented. Finally, the use of this unique sample to study genotype and environment interactions is described. (C) 2008, Elsevier Inc. C1 [Govindaraju, Diddahally R.; Atwood, Larry D.; Wolf, Philip A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Cupples, L. Adrienne; Atwood, Larry D.; D'Agostino, Ralph B., Sr.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Kannel, William B.; O'Donnell, Christopher J.; D'Agostino, Ralph B., Sr.; Fox, Caroline S.; Larson, Marty; Levy, Daniel; Murabito, Joanne; Vasan, Ramachandran S.; Splansky, Greta Lee; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Murabito, Joanne] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Govindaraju, DR (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. OI Murabito, Joanne/0000-0002-0192-7516; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01 HC025195, N01-HC 25195, N01HC25195, R01 HL076784, R01 HL076784-01]; NIA NIH HHS [AG028321, R01 AG028321, R01 AG028321-01] NR 128 TC 42 Z9 42 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 BN 978-0-12-374443-2 J9 ADV GENET JI Adv. Genet. PY 2008 VL 62 BP 33 EP 65 DI 10.1016/S0065-2660(08)00602-0 PG 33 WC Genetics & Heredity SC Genetics & Heredity GA BQB46 UT WOS:000280569200002 PM 19010253 ER PT S AU Rivera, J Fierro, NA Olivera, A Suzuki, R AF Rivera, Juan Fierro, Nora A. Olivera, Ana Suzuki, Ryo BE Alt, FW TI New insights on mast cell activation via the high affinity receptor for IgE SO ADVANCES IN IMMUNOLOGY, VOL 98 SE Advances in Immunology LA English DT Review; Book Chapter DE calcium; Fc epsilon RI; IgE; kinase; mast cell ID FC-EPSILON-RI; TYROSINE KINASE SYK; OPERATED CA2+ ENTRY; SRC FAMILY KINASES; LYN-DEFICIENT MICE; NEGATIVE REGULATION; SPHINGOSINE KINASE; LIPID RAFTS; CYTOKINE PRODUCTION; PLASMA-MEMBRANE AB Mast cells are innate immune cells that function as regulatory or effector cells and serve to amplify adaptive immunity. In adaptive immunity these cells function primarily through cell surface Fc receptors that bind immunoglobulin antibodies. The dysregulation of their adaptive role makes them central players in allergy and asthma. Upon encountering an allergen (antigen), which is recognized by immunoglobulin E (IgE) antibodies bound to the high affinity IgE receptor (Fc epsilon RI) expressed on their cell surface, mast cells secrete both preformed and newly synthesized mediators of the allergic response, Blocking of these responses is an objective in therapeutic intervention of allergic diseases. Thus, understanding the mechanisms by which antigens elicit mast cell activation (via Fc epsilon RI) holds promise toward identifying therapeutic targets. Here we review the most recent advances in understanding antigen-dependent mast cell activation. Specifically, we focus on the requirements for Fc epsilon RI activation, the regulation of calcium responses, co-stimulatory signals in Fc epsilon RI-mediated mast cell activation and function, and how genetics influences mast cell signaling and responses. These recent discoveries open new avenues of investigation with therapeutic potential. (c) 2008 Elsevier Inc. C1 [Rivera, Juan; Fierro, Nora A.; Olivera, Ana; Suzuki, Ryo] NIAMSD, Lab Immune Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMSD, Lab Immune Cell Signaling, NIH, Bethesda, MD 20892 USA. FU National Institutes of Health FX The research of the authors reported herein was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health NR 129 TC 93 Z9 97 U1 3 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-374331-2 J9 ADV IMMUNOL JI Adv.Immunol. PY 2008 VL 98 BP 85 EP 120 DI 10.1016/S0065-2776(08)00403-3 PG 36 WC Immunology SC Immunology GA BIH29 UT WOS:000259482100003 PM 18772004 ER PT S AU Pham, TD Wang, HH Zhou, X Beck, D Brandl, M Hoehn, G Azok, J Brennan, ML Hazen, SL Wong, STC AF Pham, Tuan D. Wang, Honghui Zhou, Xiaobo Beck, Dominik Brandl, Miriam Hoehn, Gerard Azok, Joseph Brennan, Marie-Luise Hazen, Stanley L. Wong, Stephen T. C. BE Perner, P Salvetti, O TI Classification of mass spectrometry based protein markers by kriging error matching SO ADVANCES IN MASS DATA ANALYSIS OF IMAGES AND SIGNALS IN MEDICINE, BIOTECHNOLOGY, CHEMISTRY AND FOOD INDUSTRY, PRCEEDINGS SE Lecture Notes in Artificial Intelligence LA English DT Proceedings Paper CT 3rd International Conference on Mass Data Analysis of Signal and Images in Medicine, Biotechnology, Chemistry and Food Industry CY JUL 14, 2008 CL Leipzig, GERMANY DE bioinformatics; pattern classification; biomarker discovery; proteomics; mass spectrometry data; geostatistics ID BIOMARKER DISCOVERY; OVARIAN-CANCER; PROTEOMIC PATTERNS; HUMAN SERUM AB Discovery of biomarkers using serum proteomic patterns is currently one of the most attractive interdisciplinary research areas in computational life science. This new proteomic approach has the clinical significance in being able to detect disease in its early stages and to develop new drugs for disease treatment and prevention. This paper introduces a novel pattern classification strategy for identifying protein biomarkers using mass spectrometry data of blood samples collected from patients in emergency department monitored for major adverse cardiac events within six months. We applied the theory of geostatistics and a kriging error matching scheme for identifying protein biomarkers that are able to provide an average classification rate superior to other current methods. The proposed strategy is very promising, as a general computational bioinformatic model for proteomic-pattern based biomarker discovery. C1 [Pham, Tuan D.; Beck, Dominik; Brandl, Miriam] James Cook Univ, Bioinformat Applicat Res Ctr, Townsville, Qld 4811, Australia. [Wang, Honghui; Hoehn, Gerard; Azok, Joseph] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Zhou, Xiaobo; Wong, Stephen T. C.] Methodist Hosp Res, Weill Cornell Med Coll, Dept Radiol, Houston, TX USA. [Brennan, Marie-Luise; Hazen, Stanley L.] Cleveland Clin Fdn, Ctr Cardiovasc Diag & Prevent, Cleveland, OH 44195 USA. RP Pham, TD (reprint author), James Cook Univ, Bioinformat Applicat Res Ctr, Townsville, Qld 4811, Australia. RI Salvetti, Ovidio/C-4891-2015 NR 32 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 978-3-540-70714-1 J9 LECT NOTES ARTIF INT PY 2008 VL 5108 BP 82 EP + PG 4 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BIC50 UT WOS:000258397100008 ER PT S AU Ruiz, ME Neveol, A AF Ruiz, Miguel E. Neveol, Aurelie BE Peters, C Jikoun, V Mandl, T Muller, H Oard, DW Penas, A Petras, V Santos, D TI Evaluation of Automatically Assigned MeSH Terms for Retrieval of Medical Images SO ADVANCES IN MULTILINGUAL AND MULTIMODAL INFORMATION RETRIEVAL SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 8th Workshop of the Cross-Language Evaluation Forum CY SEP 19-21, 2007 CL Budapest, HUNGARY AB This paper presents the results of the State University of New York at Buffalo (UB) team in collaboration with the National Library of Medicine (NLM) in the 2007 ImageCLEFmed task. We use a system that combines visual features (using a CBIR System) and text retrieval. We used the Medical Text Indexer (MTI) developed by NLM to automatically assign MeSH terms and UMLS concepts to the English free text annotations of the images. We also used an equivalent system called MAIF that automatically assigns MeSH and UMLS concepts to French free text. Our results indicate that the use of automatically assigned UMLS concepts improves retrieval performance significantly. We also identified specific aspects of the system that could be improved in the future, such as the method used to perform the automatic translation of medical terms and the addition of image classification to process queries targeted to a specific image modality. C1 [Ruiz, Miguel E.] Univ N Texas, Sch Lib & Informat Sci, POB 311068, Denton, TX 76203 USA. [Neveol, Aurelie] Natl Lib Med, Bethesda, MD 20894 USA. RP Ruiz, ME (reprint author), Univ N Texas, Sch Lib & Informat Sci, POB 311068, Denton, TX 76203 USA. EM meruiz@unt.edu; neveola@mail.nih.gov FU Oak Ridge Institute for Science and Education trhough an interagency agreement between the U.S; Department of Energy and the National Library of Medicine FX This work was supported in part by an appointment of A. Neveol and M. E. Ruiz to the NLM Research Participation Program. This program is administered by the Oak Ridge Institute for Science and Education trhough an interagency agreement between the U.S. Department of Energy and the National Library of Medicine. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-85759-4 J9 LECT NOTES COMPUT SC PY 2008 VL 5152 BP 641 EP + PG 3 WC Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BIK64 UT WOS:000260420000082 ER PT S AU McKenzie, FE Smith, DL O'Meara, WP Riley, EM AF McKenzie, F. Ellis Smith, David L. O'Meara, Wendy P. Riley, Eleanor M. BE Rollinson, D Hay, SI TI Strain theory of malaria: The first 50 years SO ADVANCES IN PARASITOLOGY, VOL 66 SE Advances in Parasitology LA English DT Review; Book Chapter ID PARASITE PLASMODIUM-FALCIPARUM; ANTIMALARIAL-DRUG RESISTANCE; VIVAX INFECTION; GENETIC-CHARACTERIZATION; SEQUENCE DIVERSITY; GENERAL PARALYSIS; CLINICAL IMMUNITY; UNSTABLE MALARIA; CLONED LINES; TRANSMISSION AB From the 1920s to the 1970s, a large body of principles and evidence accumulated about the existence and character of 'strains' among the Plasmodium species responsible for human malaria. An extensive research literature examined the degree to which strains were autonomous, stable biological entities, distinguishable by clinical, epidemiological or other features, and how this knowledge could be used to benefit medical and public health practice. Strain theory in this era was based largely on parasite phenotypes related to clinical virulence, reactions to anti-malarial drugs, infectivity to mosquitoes, antigenic properties and host immunity, latency and relapse. Here we review the search for a definition of 'strain', suggest how the data and discussion shaped current understandings of many aspects of malaria and sketch a number of specific connections with perspectives from the past 30 years. C1 [McKenzie, F. Ellis; O'Meara, Wendy P.] Fogarty Int Ctr Natl, NIH, Bethesda, MD 20892 USA. [Smith, David L.] Univ Florida, Dept Zool, Gainesville, FL 32611 USA. [Smith, David L.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. [Riley, Eleanor M.] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. RP McKenzie, FE (reprint author), Fogarty Int Ctr Natl, NIH, Bldg 16, Bethesda, MD 20892 USA. RI Riley, Eleanor/C-8960-2013; Smith, David/L-8850-2013 OI Riley, Eleanor/0000-0003-3447-3570; Smith, David/0000-0003-4367-3849 FU Intramural NIH HHS [Z99 TW999999] NR 190 TC 26 Z9 26 U1 3 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-308X BN 978-0-12-374229-2 J9 ADV PARASIT JI Adv.Parasitol. PY 2008 VL 66 BP 1 EP 46 DI 10.1016/S0065-308X(08)00201-7 PG 46 WC Parasitology SC Parasitology GA BHX08 UT WOS:000257139000001 PM 18486688 ER PT S AU Aguilera, G Subburaju, S Young, S Chen, J AF Aguilera, Greti Subburaju, Sivan Young, Sharla Chen, Jun BE Neumann, ID Landgraf, R TI The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress SO ADVANCES IN VASOPRESSIN AND OXYTOCIN: FROM GENES TO BEHAVIOUR TO DISEASE SE Progress in Brain Research LA English DT Review CT 7th World Congress on Neurohypophysial Hormones CY SEP 18-22, 2007 CL Regensburg, GERMANY DE vasopressin; corticotrophin-releasing hormone; ACTH secretion; hypothalamic paraventricular nucleus; stress; adrenalectomy; pituitary mitogenesis ID CORTICOTROPIN-RELEASING HORMONE; HYPOPHYSEAL PORTAL BLOOD; INSULIN-INDUCED HYPOGLYCEMIA; V-1B RECEPTOR ANTAGONIST; RAT ANTERIOR-PITUITARY; ARGININE-VASOPRESSIN; REPEATED RESTRAINT; ADRENOCORTICOTROPIN SECRETION; CELL-PROLIFERATION; DIABETES-INSIPIDUS AB Vasopressin (VP) secreted from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) stimulates pituitary adrenocorticotropic hormone (ACTH) secretion, through interaction with receptors of the V1b subtype (V1bR) in the pituitary corticotroph, mainly by potentiating the stimulatory effects of corticotrophin-releasing hormone (CRH). Chronic stress paradigms associated with corticotroph hyperresponsiveness lead to preferential expression of hypothalamic VP over CRH and upregulation of pituitary V1bR, suggesting that VP has a primary role during adaptation of the hypothalamic pituitary adrenal (HPA) axis to long-term stimulation. However, studies using pharmacological or genetic ablation of V1bR have shown that VP is required for full ACTH responses to some stressors, but not for the sensitization of ACTH responses to a novel stress observed during chronic stress. Studies using minipump infusion of a peptide V1 antagonist in long-term adrenalectomized rats have revealed that VP mediates proliferative responses in the pituitary. Nevertheless, only a minor proportion of cells undergoing mitogenesis co-express markers for differentiated corticotrophs or precursors, suggesting that new corticotrophs are recruited from yet undifferentiated cells. The overall evidence supports a limited role of VP regulating acute ACTH responses to some acute stressors and points to cell proliferation and pituitary remodelling as alternative roles for the marked increases in parvocellular vasopressinergic activity during prolonged activation of the HPA axis. C1 [Aguilera, Greti; Subburaju, Sivan; Young, Sharla; Chen, Jun] NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM Greti_Aguilera@nih.gov FU NIH/NICHD FX This work was supported by the Intramural Research Program of the NIH/NICHD. NR 70 TC 58 Z9 60 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53201-5 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2008 VL 170 BP 29 EP 39 DI 10.1016/S0079-6123(08)00403-2 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BQC11 UT WOS:000280617500004 PM 18655869 ER PT S AU Scordalakes, EM Yue, CM Gainer, H AF Scordalakes, Elka M. Yue, Chunmei Gainer, Harold BE Neumann, ID Landgraf, R TI Experimental approaches for the study of oxytocin and vasopressin gene expression in the central nervous system SO ADVANCES IN VASOPRESSIN AND OXYTOCIN: FROM GENES TO BEHAVIOUR TO DISEASE SE Progress in Brain Research LA English DT Review CT 7th World Congress on Neurohypophysial Hormones CY SEP 18-22, 2007 CL Regensburg, GERMANY DE oxytocin; vasopressin; gene expression; glutamate; heteronuclear RNA; alzet osmotic mini-pumps; osmotic regulation ID VASCULOSUM LAMINA TERMINALIS; RAT SUPRAOPTIC NEURONS; INTRON-SPECIFIC PROBES; NON-NMDA RECEPTORS; OSMOTIC STIMULATION; MESSENGER-RNA; HYPOTHALAMONEUROHYPOPHYSEAL EXPLANTS; MAGNOCELLULAR NEURONS; INSITU HYBRIDIZATION; SYNAPTIC ACTIVATION AB Intron-specific probes measure heteronuclear RNA (hnRNA) levels and thus approximate the transcription rates of genes, in part because of the rapid turnover of this intermediate form of RNA in the cell nucleus. Previously, we used oxytocin (Oxt)- and vasopressin (Avp)-intron-specific riboprobes to measure changes in Oxt and Avp hnRNA levels in the supraoptic nucleus (SON) by quantitative in situ hybridization (ISH) after various classical physiological perturbations, including acute and chronic salt loading, and lactation. In the present experiments, we used a novel experimental model to study the neurotransmitter regulation of Oxt and Avp gene expression in the rat SON in vivo. Bilateral cannulae connected via tubing to Alzet osmotic mini-pumps were positioned over the SON. In every experiment, one SON was infused with PBS and served as the control SON in each animal, and the contralateral SON received infusions of various neurotransmitter agonists and antagonists. Using this approach, we found that Avp but not Oxt gene expression increased after acute (2-5 h) combined excitatory amino acid agonist and GABA antagonist treatment, similar to what we found after an acute hyperosmotic stimulus. Since both OXT and AVP are known to be comparably and robustly secreted in response to acute osmotic stimuli in vivo and glutamate agonists in vitro, our results indicate a dissociation between OXT secretion and Oxt gene transcription in vivo. C1 [Scordalakes, Elka M.; Yue, Chunmei; Gainer, Harold] NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Scordalakes, Elka M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov FU NIH, NINDS FX We thank Dr. Tal Shahar for his help in establishing the surgical technique in our laboratory, and Dr. Noriko Mutsuga for her technical assistance in ISH. This research was supported by the Intramural Research Program of the NIH, NINDS. NR 33 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53201-5 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2008 VL 170 BP 43 EP 51 DI 10.1016/S0079-6123(08)00404-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA BQC11 UT WOS:000280617500005 PM 18655870 ER PT S AU Caldwell, HK Wersinger, SR Young, WS AF Caldwell, Heather K. Wersinger, Scott R. Young, W. Scott, III BE Neumann, ID Landgraf, R TI The role of the vasopressin 1b receptor in aggression and other social behaviours SO ADVANCES IN VASOPRESSIN AND OXYTOCIN: FROM GENES TO BEHAVIOUR TO DISEASE SE Progress in Brain Research LA English DT Review CT 7th World Congress on Neurohypophysial Hormones CY SEP 18-22, 2007 CL Regensburg, GERMANY DE vasopressin; vasopressin 1b receptor; aggression; social memory; social recognition; social motivation; hippocampus ID GONADAL-STEROIDS INFLUENCE; STRESS-RELATED DISORDERS; TEMPORAL-LOBE EPILEPSY; V-1B RECEPTOR; KNOCKOUT MICE; V1B RECEPTOR; PITUITARY-GLAND; RAT-BRAIN; SEPTUM; HIPPOCAMPUS AB While the importance of vasopressin (Avp) in the neuroendocrine regulation of behaviour is clear, most of Avp's effects on behaviour have been linked to its action via its 1a receptor (Avpr1a) subtype. There is, however, emerging evidence and cross-species consensus that the vasopressin 1b receptor (Avpr1b) is also important in mediating the effects of Avp on behaviour. The Avpr1b is highly expressed in the anterior pituitary where it is thought to play a role in the neuroendocrine response to stress. The Avpr1b is also prominently expressed in the pyramidal cells of the CA2 hippocampal area. Interestingly, in mice, Avpr1b mRNA within the pyramidal neurons of the CA2 field is unaffected by restraint stress or adrenalectomy. Avpr1b knockout mice (-/-) have provided strong, consistent evidence that the Avpr1b plays a critical role in the regulation of social behaviour. Avpr1b(-/-) mice display reduced levels of social forms of aggression, reduced social motivation and impaired social memory (including the Bruce effect). Avpr1b(-/-) mice, however, have normal main olfactory ability, spatial memory and defensive and predatory behaviours. Mice lacking a functional accessory olfactory system display many of these same behavioural deficits, suggesting that Avpr1b(-/-) mice may have a deficit in the processing, perception and/or integration of olfactory stimuli detected by the accessory olfactory system. We suggest that the role of the Avpr1b is to couple socially relevant accessory olfactory cues with the appropriate behavioural response. Furthermore, given its prominence in the CA2 field of the hippocampus, we hypothesize that Avpr1b may be important for the formation or recall of memories that have an olfactory-based social component. C1 [Caldwell, Heather K.] Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA. [Wersinger, Scott R.] SUNY Buffalo, Dept Psychol, Buffalo, NY USA. [Young, W. Scott, III] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. RP Caldwell, HK (reprint author), Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA. EM hcaldwel@kent.edu; wsy@mail.nih.gov RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NIMH [Z01-MH-002498-17] FX This work was supported by the NIMH Intramural Research Program (Z01-MH-002498-17). NR 51 TC 32 Z9 33 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53201-5 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2008 VL 170 BP 65 EP 72 DI 10.1016/S0079-6123(08)00406-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BQC11 UT WOS:000280617500007 PM 18655872 ER PT S AU Lee, HJ Caldwell, HK Macbeth, AH Young, WS AF Lee, Heon-Jin Caldwell, Heather K. Macbeth, Abbe H. Young, W. Scott, III BE Neumann, ID Landgraf, R TI Behavioural studies using temporal and spatial inactivation of the oxytocin receptor SO ADVANCES IN VASOPRESSIN AND OXYTOCIN: FROM GENES TO BEHAVIOUR TO DISEASE SE Progress in Brain Research LA English DT Review CT 7th World Congress on Neurohypophysial Hormones CY SEP 18-22, 2007 CL Regensburg, GERMANY DE oxytocin; Oxtr; conditional; knockout; behaviour; transgenic; Camk2a; Cre ID GENE-EXPRESSION; DEFICIENT MICE; MOUSE-BRAIN; STEM-CELLS; AUTISM; RECOMBINATION; PARTURITION; ASSOCIATION; SCREEN; SYSTEM AB Oxytocin (Oxt), synthesized in magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei for transport to and release from the posterior pituitary, is released during parturition and is essential for lactation. Lesser amounts of Oxt are made by smaller cells of the PVN and a few other forebrain nuclei and released into the central nervous system (CNS) to influence various other behaviours. In both the periphery and CNS, Oxt actions are transduced by the oxytocin receptor (Oxtr). Previously, it has been reported that Oxt(-/-) (knockout, KO) mice show a failure of milk ejection and thus are incapable of rearing their offspring. Unexpectedly, these mice have largely normal reproductive and maternal behaviours, perhaps due to compensatory mechanisms through activation of the Oxtr by vasopressin or through development. To examine the specific roles of the Oxtr during development and in particular brain areas, we created conditional Oxtr(-/-) mice in which we could control the spatial and temporal inactivation of the Oxtr. We flanked the neomycin-resistance selectable marker in an Oxtr intron with FRT sites to enable its removal using FLP recombinase. Coding sequence within exons 2 and 3 was flanked by two loxP sites enabling subsequent inactivation of the gene by targeted expression of Cre recombinase. The first Oxtr KO lines we created have either total or relatively specific forebrain elimination. The latter was achieved by crossing the conditional Oxtr line with a transgenic line in which the Camk2a promoter drives expression of Cre recombinase to significant levels beginning 21-28 days after birth, thus eliminating potential compensation for a deleted Oxtr gene during early development. This Cre-expressing line also significantly spares the main olfactory bulb reducing the potential confound of an olfactory deficit. We have investigated various behaviours, most notably social recognition, in both Oxtr KO strains (Oxtr(-/-) and Oxtr(FB/FB)). C1 [Lee, Heon-Jin; Macbeth, Abbe H.; Young, W. Scott, III] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. [Caldwell, Heather K.] Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA. RP Young, WS (reprint author), NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009; OI Young, W Scott/0000-0001-6614-5112; , Heon-Jin/0000-0002-1911-5014 FU NIMH [Z01-MH-002498-17] FX This work was supported by the NIMH Intramural Research Programme (Z01-MH-002498-17). NR 26 TC 25 Z9 25 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53201-5 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2008 VL 170 BP 73 EP 77 DI 10.1016/S0079-6123(08)00407-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA BQC11 UT WOS:000280617500008 PM 18655873 ER PT S AU Gottwein, JM Bukh, J AF Gottwein, Judith M. Bukh, Jens BE Maramorosch, K Shatkin, AJ Murphy, FA TI Cutting the gordian knot-development and biological relevance of hepatitis C virus cell culture systems SO ADVANCES IN VIRUS RESEARCH, VOL 71 SE Advances in Virus Research LA English DT Review; Book Chapter ID DEPENDENT RNA-POLYMERASE; NONSTRUCTURAL PROTEIN 5A; B TYPE-I; RIBOSOME ENTRY SITE; HUMAN MONOCLONAL-ANTIBODIES; INFECTIOUS MOLECULAR CLONE; E2 ENVELOPE GLYCOPROTEINS; HIGH-DENSITY-LIPOPROTEIN; SCAVENGER RECEPTOR-BI; HUMAN HEPATOMA-CELLS C1 [Gottwein, Judith M.; Bukh, Jens] Copenhagen Univ Hosp, Copenhagen Hepatitis C Program CO HEP, Dept Infect Dis & Clin Res Ctr, Hvidovre, Denmark. [Bukh, Jens] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Fac Hlth Sci, DK-1168 Copenhagen, Denmark. [Bukh, Jens] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Gottwein, JM (reprint author), Copenhagen Univ Hosp, Copenhagen Hepatitis C Program CO HEP, Dept Infect Dis & Clin Res Ctr, Hvidovre, Denmark. NR 506 TC 64 Z9 64 U1 1 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 BN 978-0-12-374321-3 J9 ADV VIRUS RES JI Adv.Virus Res. PY 2008 VL 71 BP 51 EP + DI 10.1016/S0065-3527(08)00002-X PG 87 WC Virology SC Virology GA BIA84 UT WOS:000257981300002 PM 18585527 ER PT S AU McBride, AA AF McBride, Alison A. BE Maramorosch, K Shatkin, A Murphy, F TI Replication and Partitioning of Papillomavirus Genomes SO ADVANCES IN VIRUS RESEARCH, VOL 72 SE Advances in Virus Research LA English DT Review; Book Chapter ID EPSTEIN-BARR-VIRUS; DNA-BINDING DOMAIN; SARCOMA-ASSOCIATED HERPESVIRUS; TYPE-1 E2 PROTEIN; CCAAT DISPLACEMENT PROTEIN; COTTONTAIL RABBIT PAPILLOMAVIRUS; NUCLEAR-LOCALIZATION SIGNAL; HOST MITOTIC CHROMOSOMES; HPV18 REGULATORY REGION; KERATINOCYTE CELL-LINE AB Papillomaviruses establish persistent infection in the dividing, basal epithelial cells of the host. The viral genome is maintained as a circular, double-stranded DNA, extrachromosomal element within these cells. Viral genome amplification occurs only when the epithelial cells differentiate and viral particles are shed in squames that are sloughed from the surface of the epithelium. There are three modes of replication in the papillomavirus life cycle, Upon entry, in the establishment phase, the viral genome is amplified to a low copy number, in the second maintenance phase, the genome replicates in dividing cells at a constant copy number, in synchrony with the cellular DNA. And finally, in the vegetative or productive phase, the viral DNA is amplified to a high copy number in differentiated cells and is destined to be packaged in viral capsids. This review discusses the cis elements and protein factors required for each stage of papillomavirus replication, C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI McBride, Alison/0000-0001-5607-5157 FU NIH; NIAID FX The authors research is supported by the Intramural Research Program of the NIH, NIAID. NR 276 TC 43 Z9 43 U1 2 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 BN 978-0-12-374322-0 J9 ADV VIRUS RES JI Adv.Virus Res. PY 2008 VL 72 BP 155 EP 205 PG 51 WC Virology SC Virology GA BIO90 UT WOS:000261402300004 PM 19081491 ER PT J AU Ocama, P Katwere, M Piloya, T Feld, J Opio, KC Kambugu, A Katabira, E Thomas, D Colebunders, R Ronald, A AF Ocama, Ponsiano Katwere, Michael Piloya, Theresa Feld, Jordan Opio, Kenneth C. Kambugu, Andrew Katabira, Elly Thomas, David Colebunders, Robert Ronald, Allan TI The spectrum of liver diseases in HIV infected individuals at an HIV treatment clinic in Kampala, Uganda SO AFRICAN HEALTH SCIENCES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C; ANTIRETROVIRAL THERAPY; B-VIRUS; HEPATOTOXICITY; COINFECTION AB Background: Liver diseases are common in patients with HIV due to viral hepatitis B and C co-infections, opportunistic infections or malignancies, antiretroviral drugs and drugs for opportunistic infections. Objective: To describe the spectrum of liver diseases in HIV-infected patients attending an HIV clinic in Kampala, Uganda. Method: Consecutive patients presenting with jaundice, right upper quadrant pain with fever or malaise, ascites and/or tender hepatomegaly were recruited and underwent investigations to evaluate the cause of their liver disease. Results: Seventy-seven consecutive patients were recruited over an eleven month period. Of these, 23 (30%) had increased transaminases because of nevirapine (NVP) and/or isoniazid (INH) hepatotoxicity. Although 14 (61%) patients with drug-induced liver disease presented with jaundice, all recovered with drug discontinuation. Hepatitis B surface antigen was positive in 11 (15%) patients while anti-hepatitis C antibody was reactive in only 2 (3%). Probable granulomatous hepatitis due to tuberculosis was diagnosed in 7 (9%) patients and all responded to anti-TB therapy. Other diagnoses included alcoholic liver disease, AIDS cholangiopathy, hepatocellular carcinoma, schistosomiasis, haemangioma and hepatic adenoma. Twelve (16%) patients died during follow-up of which 7 (9%) died because of liver disease. Conclusion: Drug history, liver enzyme studies, ultrasound, and hepatitis B and C investigations identified the probable etiology in 60 (78%) of 77 patients with HIV infection presenting with symptoms and/or signs of liver disease. African Health Sciences 2008; 8(1): 8-12 C1 [Ocama, Ponsiano; Katwere, Michael; Piloya, Theresa; Kambugu, Andrew; Katabira, Elly; Ronald, Allan] Infect Dis Inst, Kampala, Uganda. [Feld, Jordan] NIDDK, Bethesda, MD 20892 USA. [Opio, Kenneth C.] Makerere Univ, Dept Med, Kampala, Uganda. [Thomas, David] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Colebunders, Robert] Univ Antwerp, Antwerp, Belgium. RP Ocama, P (reprint author), Infect Dis Inst, POB 22418, Kampala, Uganda. EM pocama@idi.co.ug OI Ronald, Allan/0000-0002-5746-3490 NR 17 TC 20 Z9 20 U1 3 U2 4 PU MAKERERE UNIV, FAC MED PI KAMPALA PA PO BOX 7072, KAMPALA, 00000, UGANDA SN 1680-6905 J9 AFR HEALTH SCI JI Afr. Health Sci. PY 2008 VL 8 IS 1 BP 8 EP 12 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 528TG UT WOS:000272469300004 PM 19357726 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Hormesis defined SO AGEING RESEARCH REVIEWS LA English DT Review DE adaptive stress response; exercise; histone deacetylase; phytochemicals; preconditioning; toxic ID CALORIC RESTRICTION; OXIDATIVE STRESS; NEURODEGENERATIVE DISORDERS; DOSE RESPONSES; CANCER; MECHANISMS; PREVENTION; HYPOTHESIS; PLASTICITY; PRODUCTS AB Hormesis is a term used by toxicologists to refer to a biphasic dose-response to an environmental agent characterized by a low dose stimulation or beneficial effect and a high dose inhibitory or toxic effect. In the fields of biology and medicine hormesis is defined as an adaptive response of cells and organisms to a moderate (usually intermittent) stress. Examples include ischemic preconditioning, exercise, dietary energy restriction and exposures to low doses of certain phytochemicals. Recent findings have elucidated the cellular signaling pathways and molecular mechanisms that mediate hormetic responses which typically involve enzymes such as kinases and deacetylases, and transcription factors such as Nrf-2 and NF-kappa B. As a result, cells increase their production of cytoprotective and restorative proteins including growth factors, phase 2 and antioxidant enzymes, and protein chaperones. A better understanding of hormesis mechanisms at the cellular and molecular levels is leading to and to novel approaches for the prevention and treatment of many different diseases. Published by Elsevier Ireland Ltd. C1 [Mattson, Mark P.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000314-07, Z01 AG000315-07] NR 49 TC 295 Z9 304 U1 10 U2 64 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD JAN PY 2008 VL 7 IS 1 BP 1 EP 7 DI 10.1016/j.arr.2007.08.007 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 261TW UT WOS:000253103900001 PM 18162444 ER PT J AU Marini, AM Jiang, H Pan, H Wu, X Lipsky, RH AF Marini, Ann M. Jiang, Hong Pan, Hongna Wu, Xuan Lipsky, Robert H. TI Hormesis: A promising strategy to sustain endogenous neuronal survival pathways against neurodegenerative disorders SO AGEING RESEARCH REVIEWS LA English DT Review DE NMDA receptors; brain; rat; hormesis; stress; BDNF; TrkB receptors ID METHYL-D-ASPARTATE; NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; CEREBELLAR GRANULE-CELLS; ELEMENT-BINDING PROTEIN; SIGNAL-REGULATED KINASE; LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; ACTIVITY-DEPENDENT NEUROPROTECTION; RECEPTOR-MEDIATED NEUROPROTECTION AB The brain developed adaptive mechanisms in the face of changing environments and stresses imposed on the nervous system. The addition of glutamate as the major excitatory amino acid neurotransmitter to the brain's complement of amino acids and peptides dictated a coordinated transcriptional and translational program to meet the demands of excitatory neurotransmission. One such program is the ability of neurons to sustain and maintain their survival given the nature of glutamate-mediated receptor activation. The unique development of endogenous neuronal pathways activated by glutamate receptors transformed neurons and allowed them to survive under conditions of high energy demands. These same endogenous survival pathways also mediate plastic responses to meet another demand of the brain, adaptation. An endogenous protein that plays a central role in glutamate receptor-mediated survival pathways is brain-derived neurotrophic factor (BDNF). Intermittent but frequent synaptic ionotropic glutamate receptor activation ensures neuronal survival through a BDNF autocrine loop. In sharp contrast, overactivation of ionotropic glutamate receptors leads to neuronal cell death. Thus, innovative strategies that induce endogenous neuronal survival pathways through low-level activation of ionotropic glutamate receptors or those that bypass receptor activation but upregulate endogenous survival pathways may not only prevent neurodegenerative disorders that involve glutamate as a final common pathway that kills neurons, but may also provide treatment alternatives critical for neurons to survive stressful conditions such as stroke, status epilepticus and hypoglycemic-induced neuronal cell death. Published by Elsevier Ireland Ltd. C1 [Marini, Ann M.; Jiang, Hong; Pan, Hongna; Wu, Xuan] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. [Lipsky, Robert H.] NIAAA, Neurogenet Lab, Rockville, MD USA. RP Marini, AM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Neurol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM amarini@usuhs.mil OI Lipsky, Robert/0000-0001-7753-1473 NR 148 TC 19 Z9 19 U1 2 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD JAN PY 2008 VL 7 IS 1 BP 21 EP 33 DI 10.1016/j.arr.2007.07.003 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 261TW UT WOS:000253103900003 PM 17889623 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Dietary factors, hormesis and health SO AGEING RESEARCH REVIEWS LA English DT Review DE adaptive stress response; exercise; histone deacetylase; phytochemicals; preconditioning; toxic ID CALORIC RESTRICTION IMPROVES; TRANSCRIPTION FACTOR NRF2; NEUROTROPHIC FACTOR; OXIDATIVE STRESS; BEHAVIORAL DEFICITS; PARKINSONS-DISEASE; BRAIN-DAMAGE; FACTOR-I; RATS; EXPRESSION AB The impact of dietary factors on health and longevity is increasingly appreciated. The most prominent dietary factor that affects the risk of many different chronic diseases is energy intake - excessive calorie intake increases the risk. Reducing energy intake by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against disease, in part, by hormesis mechanisms that increase cellular stress resistance. Some specific dietary components may also exert health benefits by inducing adaptive cellular stress responses. Indeed, recent findings suggest that several heavily studied phytochemicals exhibit biphasic dose responses on cells with low doses activating signaling pathways that result in increased expression of genes encoding cytoprotective proteins including antioxidant enzymes, protein chaperones, growth factors and mitochondrial proteins. Examples include: activation of the Nrf-2-ARE pathway by sulforaphane and curcumin; activation of TRP ion channels by allicin and capsaicin; and activation of sirtuin- I by resveratrol. Research that establishes dose response and kinetic characteristics of the effects of dietary factors on cells, animals and humans will lead to a better understanding of hormesis and to improvements in dietary interventions for disease prevention and treatment. Published by Elsevier Ireland Ltd. C1 [Mattson, Mark P.] NIA, Intramural Res Program, Lab Neurosci, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Lab Neurosci, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000315-07] NR 59 TC 142 Z9 145 U1 4 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD JAN PY 2008 VL 7 IS 1 BP 43 EP 48 DI 10.1016/j.arr.2007.08.004 PG 6 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 261TW UT WOS:000253103900005 PM 17913594 ER PT J AU Mellins, CA Chu, C Malee, K Allison, S Smith, R Harris, L Higgins, A Zorrilla, C Landesman, S Serchuck, L LaRussa, P AF Mellins, C. A. Chu, C. Malee, K. Allison, S. Smith, R. Harris, L. Higgins, A. Zorrilla, C. Landesman, S. Serchuck, L. LaRussa, P. TI Adherence to antiretroviral treatment among pregnant and postpartum HIV-infected women SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; pregnancy; adherence; antiretroviral treatment; women ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEDICATION ADHERENCE; GREATER ADHERENCE; NONPREGNANT WOMEN; INHIBITOR THERAPY; CONTROLLED-TRIAL; SUBSTANCE-ABUSE; MENTAL-ILLNESS; POSITIVE WOMEN; TRANSMISSION AB Among women with HIV infection, pregnancy is a time when maintenance of maternal health and reduction of vertical HIV transmission are primary concerns. Few studies have examined adherence to Antiretroviral Treatment (ART) during pregnancy and in the postpartum period when the demands of childcare may significantly interfere with women's self-care behaviors. This study examined ART use and adherence in HIV-infected pregnant and postpartum women participating in the Women and Infants Transmission Study (WITS-IV) in the US. Adherence was assessed through a self-report interview during the third trimester of pregnancy and six-month postpartum. Data were also collected on demographics, biomedical markers and health related symptoms. During the third trimester visit, 77% (309/399) of women completed the self-report adherence measure; 61% (188/309) reported complete adherence. Factors associated with non-adherence included advanced HIV disease status, higher HIV-RNA viral load, more health-related symptoms and alcohol and tobacco use. At six-month postpartum, 55% (220/399) completed the measure; 44% (97/220) of these women reported complete adherence. Factors associated with non-adherence during the postpartum period were ethnicity, more health-related symptoms and WITS clinical site. Results of multivariate analyses using Generalized Estimated Equation analyses across the two visits revealed that more health-related symptoms, higher HIV-RNA viral load, increased alcohol use and clinical site were independently associated with ART non-adherence. These analyses indicate that medication adherence is more likely during pregnancy than postpartum in HIV-infected women, perhaps provoked by motivation to reduce vertical transmission and/or intensive antepartum surveillance. Further investigation is warranted to clarify factors implicated in women's decision-making process regarding ART medication adherence. C1 [Mellins, C. A.] Columbia Univ, HIV Ctr Clin & Behav Studies, New York, NY 10027 USA. [Chu, C.] Clin Trials & Surveys Corp, Baltimore, MD USA. [Malee, K.] Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. [Allison, S.] NIMH, Bethesda, MD 20892 USA. [Smith, R.] Univ Illinois, Chicago, IL USA. [Harris, L.] Texas Childrens Hosp, Houston, TX 77030 USA. [Higgins, A.; LaRussa, P.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Zorrilla, C.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Landesman, S.] SUNY Brooklyn, New York, NY USA. [Serchuck, L.] NICHHD, Bethesda, MD 20892 USA. RP Mellins, CA (reprint author), Columbia Univ, HIV Ctr Clin & Behav Studies, New York, NY 10027 USA. EM cam14@columbia.edu FU NIAID NIH HHS [N01 AI 085339, 1 U01 AI 050274-01, U01 AI 034841, U01 AI 034858]; NICHD NIH HHS [U01 HD 041983, U01 HD 036117]; NIDA NIH HHS [U01 DA 015054, U01 DA 015053] NR 54 TC 52 Z9 53 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2008 VL 20 IS 8 BP 958 EP 968 DI 10.1080/09540120701767208 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 345DZ UT WOS:000258977600010 PM 18608073 ER PT J AU Cohn, SE Umbleja, T Mrus, J Bardeguez, AD Andersen, JW Chesney, MA AF Cohn, Susan E. Umbleja, Triin Mrus, Joseph Bardeguez, Arlene D. Andersen, Janet W. Chesney, Margaret A. TI Prior illicit drug use and missed prenatal vitamins predict nonadherence to antiretroviral therapy in pregnancy: Adherence analysis A5084 SO AIDS PATIENT CARE AND STDS LA English DT Article; Proceedings Paper CT 2nd International Conference on HIV Treatment Adherence/International-Association-of-Physicians-in-AIDS-Care CY MAR 29, 2007 CL Jersey City, NJ SP Int Assoc Phys AIDS Care ID NONPREGNANT WOMEN; PERINATAL TRANSMISSION; FERTILITY INTENTIONS; VIRAL SUPPRESSION; INHIBITOR THERAPY; UNITED-STATES; HEALTH-CARE; HIV; SMOKING; MEN AB Adherence to antiretroviral therapy (ART) in pregnancy is crucial to optimize its efficacy and minimize mother-to-child transmission. Our objective was to examine adherence patterns to ART and health behaviors during and after pregnancy among HIV-positive women enrolled in A5084, a prospective, observational, multisite study. Between 2002-2005, HIV-infected women between 20 and 34 weeks' gestation completed at least 1 self-reported adherence questionnaire antepartum (AP), and were followed through 12 weeks' postpartum (PP). Questionnaires also addressed tobacco, alcohol, and illicit drugs use. Adherence was defined as reporting not having missed any doses for more than 3 months. Exact McNemar's tests were used for paired binary data and exact logistic regression was used for predictors of nonadherence. We report on 149 women (55% black, 26% Hispanic, 32% less than 25 years, 9% with AIDS, 100% on ART). PP, 31 (21%) women stopped ART and 18 (12%) withdrew from the study. AP, 57% reported adherence to ART and PP, 45% (p = 0.03, n = 87). AP, 11% reported ongoing alcohol use and 23% tobacco use compared to 37% and 30% PP (p < 0.0001, n = 103; p = 0.07, n = 99, respectively). Although 39% ever used marijuana (n = 116) and 25% used illicit drugs (n = 107), few participants reported use during the study. In multivariate analyses, those who had ever used illicit drugs had 5.95 times higher odds (p = 0.002) and those who missed prenatal vitamins had 4.84 times higher odds (p = 0.001) of ART nonadherence. Women reporting a history of illicit drug use and/or having missed prenatal vitamins should be targeted for programs to enhance adherence to ART during pregnancy. C1 [Cohn, Susan E.] Univ Rochester, Div Infect Dis, Med Ctr, Rochester, NY 14642 USA. [Umbleja, Triin; Andersen, Janet W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mrus, Joseph] Tibotec Therapeut, Bridgewater, NJ USA. [Bardeguez, Arlene D.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Chesney, Margaret A.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. RP Cohn, SE (reprint author), Univ Rochester, Div Infect Dis, Med Ctr, 601 Elmwood Ave,Box 689, Rochester, NY 14642 USA. EM susan_cohn@urmc.rochester.edu FU NCRR NIH HHS [RR00044, RR000080, RR00043, RR00069, RR00096]; NIAID NIH HHS [AI34853, UO1 AI38558, AI27665, AI27661, AI27658, AI25915, AI25883, AI25859, AI25879, AI25897, AI25903, AI32907, AI38855, AI42845, UO1 AI41089]; NICHD NIH HHS [HD33345, N01 HD33345] NR 40 TC 17 Z9 17 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN PY 2008 VL 22 IS 1 BP 29 EP 40 DI 10.1089/apc.2007.0053 PG 12 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 256DW UT WOS:000252708900004 PM 18442305 ER PT J AU Soriano, V Heneine, W Vandamme, AM Franchini, G AF Soriano, Vincent Heneine, Walid Vandamme, Anne-Mieke Franchini, Genoveffa TI Foreword SO AIDS REVIEWS LA English DT Editorial Material C1 [Soriano, Vincent] Hosp Carlos III, Madrid, Spain. [Heneine, Walid] CDC, Atlanta, GA 30333 USA. [Vandamme, Anne-Mieke] Katholieke Univ Leuven, Rega Inst, B-3000 Louvain, Belgium. [Franchini, Genoveffa] NIH, Bethesda, MD 20892 USA. RP Soriano, V (reprint author), Hosp Carlos III, Madrid, Spain. RI Vandamme, Anne Mieke/I-4127-2012; santos, sofia/I-1637-2012 OI Vandamme, Anne Mieke/0000-0002-6594-2766; NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERMANYER PUBL PI BARCELONA PA MALLORCA, 310, BARCELONA, 00000, SPAIN SN 1139-6121 J9 AIDS REV JI Aids Rev. PD JAN-MAR PY 2008 VL 10 IS 1 BP 3 EP 3 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 287PT UT WOS:000254929700001 ER PT J AU Aseltine, RH Schilling, EA James, A Murray, M Jacobs, DG AF Aseltine, Robert H., Jr. Schilling, Elizabeth A. James, Amy Murray, Margaret Jacobs, Douglas G. TI An evaluation of National Alcohol Screening Day SO ALCOHOL AND ALCOHOLISM LA English DT Article ID IDENTIFICATION TEST AUDIT; BRIEF PHYSICIAN ADVICE; PRIMARY-CARE; EMERGENCY-DEPARTMENT; PREVENTIVE-SERVICES; BRIEF INTERVENTION; DRINKERS; TRIAL; RISK; PROJECT AB Aims: Although National Alcohol Screening Day (NASD) became the USAs largest and most visible community-based intervention targeting risky drinking over the past decade, its utility in identifying individuals who are at risk for alcohol problems and in catalyzing behaviour change has not been tested in studies including untreated controls. The purpose of this study was to assess changes in alcohol use three months following NASD participation using a quasi-experimental pretest-posttest control group design. Methods: Participants (N = 713) were recruited from 5 NASD sites in Florida, Massachusetts, and New York, USA. Intervention subjects (N = 318) were recruited at the NASD event; control subjects (N = 395) were recruited at the same locations approximately 1 week after NASD. All participants completed brief surveys at the time of enrollment, and then again 3 months later. Results: Significant decreases in the typical number of drinks consumed per occasion were observed among at-risk drinkers in the intervention group relative to controls in the 3 months following NASD. At-risk NASD participants averaged approximately 5.6 fewer drinks per week than at-risk controls. Conclusions: Findings suggest that exposure to a brief screening program with provision of feedback can result in significant reductions in alcohol consumption among risky drinkers. C1 [Schilling, Elizabeth A.; James, Amy] Univ Connecticut, Publ Hlth Res Inst, E Hartford, CT 06108 USA. [Aseltine, Robert H., Jr.] Univ Connecticut, Publ Hlth Res Inst, Div Behav Sci & Community Hlth, E Hartford, CT 06108 USA. [Murray, Margaret] NIAAA, NIH, Rockville, MD 20852 USA. [Jacobs, Douglas G.] Screening Mental Hlth Inc, Boston, MA 02115 USA. [Jacobs, Douglas G.] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. RP Aseltine, RH (reprint author), Univ Connecticut, Publ Hlth Res Inst, 99 Ash St,MC 7160, E Hartford, CT 06108 USA. EM aseltine@uchc.edu FU NIAAA NIH HHS [5U18AA012A20-05] NR 30 TC 3 Z9 3 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JAN-FEB PY 2008 VL 43 IS 1 BP 97 EP 103 DI 10.1093/alcalc/agm139 PG 7 WC Substance Abuse SC Substance Abuse GA 244KI UT WOS:000251864400017 PM 17934196 ER PT J AU Guo, QM Zakhari, S AF Guo, Q. Max Zakhari, Sam TI Commentary: Systems biology and its relevance to alcohol research SO ALCOHOL RESEARCH & HEALTH LA English DT Editorial Material DE alcohol-induced disorders; alcohol research; biomedical research; systems biology; biological systems; mathematical modeling; genomics; epigenomics; transcriptomics; metabolomics; proteomics ID GENOMICS; MEDICINE; MATRIX AB Systems biology, a new scientific discipline, aims to study the behavior of a biological organization or process in order to understand the function of a dynamic system. This commentary will put into perspective topics discussed in this issue of Alcohol Research & Health, provide insight into why alcohol-induced disorders exemplify the kinds of conditions for which a systems biological approach would be fruitful, and discuss the opportunities and challenges facing alcohol researchers. C1 [Guo, Q. Max; Zakhari, Sam] Natl Inst Alcohol Abuse & Alcoholism, Div Metab & Hlth Effects, Bethesda, MD USA. RP Guo, QM (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Div Metab & Hlth Effects, Bethesda, MD USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 1 BP 5 EP 10 PG 6 WC Substance Abuse SC Substance Abuse GA 326LH UT WOS:000257660100001 PM 23584746 ER PT J AU Gohlke, JM Hiller-Sturmhofel, S Faustman, EM AF Gohlke, Julia M. Hiller-Sturmhoefel, Susanne Faustman, Elaine M. TI A systems-based computational model of alcohol's toxic effects on brain development SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE maternal alcohol exposure; prenatal alcohol exposure; fetal alcohol effects; fetal alcohol syndrome (FAS); alcohol-related neurodevelopmental disorder (ARND); neocortex; neurogenesis; synaptogenesis; apoptosis; computational model; animal model; animal studies; human studies; systems biology ID CELL-PROLIFERATION; NEOCORTICAL NEURONOGENESIS; PRENATAL EXPOSURE; DEVELOPING MOUSE; CEREBRAL-CORTEX; ETHANOL; RAT; DEATH; NEURONS; INHIBITION AB Important stages during neurodevelopment include the generation of new nerve cells (i.e., neurogenesis), differentiation and migration of these cells to their final location in the brain, formation of connections with neighboring cells (i.e., synaptogenesis), and cell death of neurons that fail to form the appropriate connections. Research found that alcohol exposure during fetal development can interfere with all of these processes. A systems biology approach using computational models of brain development in different species has been used to determine the relative contributions of alcohol-induced impairment of neurogenesis and synaptogenesis to alcohol-related neurodevelopmental deficits in mice, rats, rhesus monkeys, and humans. The results obtained with these models suggest that alcohol's impact on cell division during neurogenesis results in greater deficits in neuron numbers in the adult than the alcohol-induced increase in cell death during synaptogenesis. In primates, the accelerated development of susceptible brain regions may convey increased sensitivity to alcohol-induced neurodevelopmental deficits. Systems-based approaches, such as the computational models described here, can help to translate research findings obtained at a molecular or cellular level in different species into assessment of risk associated with alcohol exposure during human development. C1 [Gohlke, Julia M.] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA. [Faustman, Elaine M.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. RP Gohlke, JM (reprint author), Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA. NR 37 TC 3 Z9 3 U1 0 U2 0 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 1 BP 76 EP 83 PG 8 WC Substance Abuse SC Substance Abuse GA 326LH UT WOS:000257660100009 PM 23584754 ER PT J AU Kranzler, HR Li, TK AF Kranzler, Henry R. Li, Ting-Kai TI What is addiction? SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE addiction; alcohol and other drug (AOD) use; abuse and dependence; AOD use disorders (AODUDs); substance abuse; substance dependence; Diagnostic and Statistical Manual of Mental Disorders (DSM) ID DEPENDENCE; ALCOHOL AB The issue of Alcohol Research & Health examines addiction to multiple substances-that is, combined dependence on alcohol and other drugs (AODs), including marijuana, cocaine, and opioids. It seems fitting, then, to begin the issue with a look at what constitutes 'addiction." The Oxford English Dictionary (pp. 24-25) traces the term addiction to Roman law, under which addiction was a 'formal giving over by sentence of court; hence, a dedication of person to a master." This notion of relinquishment of control by the addicted person is the central feature of many lay and professional definitions of the term. The study of addictive behavior crosses several disciplines, including, among others, behavioral neuroscience, epidemiology, genetics, molecular biology, pharmacology, psychology, psychiatry, and sociology. Articles in this issue examine aspects of AOD use disorders from the perspective of some of these varied disciplines. C1 [Kranzler, Henry R.] Univ Connecticut, Ctr Hlth, Alcohol Res Ctr, Farmington, CT 06030 USA. [Kranzler, Henry R.] Univ Connecticut, Ctr Hlth, Gen Clin Res Ctr, Farmington, CT USA. [Li, Ting-Kai] NIAAA, Bethesda, MD USA. RP Kranzler, HR (reprint author), Univ Connecticut, Ctr Hlth, Alcohol Res Ctr, Farmington, CT 06030 USA. NR 10 TC 5 Z9 5 U1 3 U2 17 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 2 BP 93 EP 95 PG 3 WC Substance Abuse SC Substance Abuse GA 347VP UT WOS:000259169800001 PM 23584810 ER PT J AU Falk, D Yi, HY Hiller-Sturmhofel, S AF Falk, Daniel Yi, Hsiao-Ye Hiller-Sturmhofel, Susanne TI An epidemiologic analysis of co-occurring alcohol and drug, use and disorders SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE National Epidemiologic Survey on Alcohol and Related Conditions (NESARC); alcohol use; drug use; alcohol use disorders (AUDs); drug use disorders (DUDs); co-morbidity; prevalence; epidemiology; racial/ethnic differences; gender differences ID DSM-IV ALCOHOL; PSYCHIATRIC-DISORDERS; UNITED-STATES; MENTAL-HEALTH; COMORBIDITY; ABUSE; DEPENDENCE; POPULATION; PREVALENCE; TOBACCO AB The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) sought to determine the prevalence of alcohol use and alcohol use disorders (AUDs), other drug use and drug use disorders (DUDs), and co-use and co-morbidity in the general adult U.S. population. Findings indicate that 5.6 percent of U.S. adults used both alcohol and drugs in the past year and that 1.1 percent had a co-morbid AUD and DUD. Alcohol use prevalence peaked between the ages of 25 and 44 and declined thereafter. The prevalence of other drug use, co-use, AUDs, DUDs, and co-morbid disorders was highest between the ages of 18 and 24 and declined steadily thereafter. Women and men showed similar trends for alcohol use, drug use, and co-use. Among ethnic/racial groups evaluated, Whites displayed the highest rates of alcohol use and American Indians/Alaskan Natives the highest rates of drug use. For AUDs, DUDs, and co-morbid disorders, rates were highest among American Indians/Alaskan Natives. The prevalence of drug use, weekly drug use, and DUDs increased with increasing levels of alcohol consumption and the presence of AUDs. The proportion of people with AUDs who had a co-morbid DUD varied considerably by drug type. These findings have important implications for the development of prevention and intervention approaches. C1 [Falk, Daniel; Yi, Hsiao-Ye] NIAAA, Arlington, VA 22201 USA. RP Falk, D (reprint author), NIAAA, Arlington, VA 22201 USA. NR 22 TC 33 Z9 33 U1 2 U2 9 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 EI 1930-0573 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 2 BP 100 EP 110 PG 11 WC Substance Abuse SC Substance Abuse GA 347VP UT WOS:000259169800003 PM 23584812 ER PT J AU Lovinger, DM AF Lovinger, David M. TI Communication Networks in the Brain Neurons, Receptors, Neurotransmitters, and Alcohol SO ALCOHOL RESEARCH & HEALTH LA English DT Review DE Alcohol and other drug effects and consequences; brain; neurons; neuronal signaling; synaptic transmission; neurotransmitter receptors; neurotrophins; steroid hormones; gamma-aminobutyric acid (GABA); glutamate; dopamine; adenosine; serotonin; opioids; endocannabinoids ID CEREBELLAR GRANULE NEURONS; CORTICOTROPIN-RELEASING-FACTOR; CHRONIC ETHANOL-CONSUMPTION; MIDBRAIN DOPAMINE NEURONS; VENTRAL TEGMENTAL AREA; CENTRAL-NERVOUS-SYSTEM; NEUROTROPHIC FACTOR; GABA(A) RECEPTORS; RAT HIPPOCAMPUS; CANNABINOID RECEPTORS AB Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other. Communication between neurons occurs at tiny gaps called synapses, where specialized parts of the two cells (i.e., the presynaptic and postsynaptic neurons) come within nanometers of one another to allow for chemical transmission. The presynaptic neuron releases a chemical (i.e., a neuro transmitter) that is received by the postsynaptic neuron's specialized proteins called neurotransmitter receptors. The neurotransmitter molecules bind to the receptor proteins and alter postsynaptic neuronal function. Two types of neurotransmitter receptors exist-ligand-gated ion channels, which permit rapid ion flow directly across the outer cell membrane, and G-protein-coupled receptors, which set into motion chemical signaling events within the cell. Hundreds of molecules are known to act as neuro transmitters in the brain. Neuronal development and function also are affected by peptides known as neurotrophins and by steroid hormones, This article reviews the chemical nature, neuronal actions, receptor subtypes, and therapeutic roles of several transmitters, neurotrophins, and hormones. It focuses on neurotransmitters with important roles in acute and chronic alcohol effects on the brain, such as those that contribute to intoxication, tolerance, dependence, and neurotoxicity, as well as maintained alcohol drinking and addiction. C1 NIAAA, Lab Integrat Neurosci, Bethesda, MD USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Bethesda, MD USA. NR 141 TC 15 Z9 15 U1 3 U2 20 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 3 BP 196 EP 214 PG 19 WC Substance Abuse SC Substance Abuse GA 374TL UT WOS:000261066500002 PM 23584863 ER PT J AU Thanos, PK Wang, GJ Volkow, ND AF Thanos, Panayotis K. Wang, Gene-Jack Volkow, Nora D. TI POSITRON EMISSION TOMOGRAPHY AS A TOOL FOR STUDYING ALCOHOL ABUSE SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE Alcohol-related research; alcohol and other drug (AOD) effects and consequences; brain; brain function; brain imaging; positron emission tomography (PET); radiotracers; radioisotopes; ((18)F)-fluoro-2-deoxyglucose (FDG); neurotransmitters; human studies; animal studies ID BRAIN GLUCOSE-METABOLISM; DOPAMINE-D-2 RECEPTORS; DETOXIFIED ALCOHOLICS; VENTRAL STRIATUM; RAT MODEL; PET; MICE; HYPERACTIVITY; INTOXICATION; DEPENDENCE C1 [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, Bethesda, MD USA. [Thanos, Panayotis K.] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Thanos, PK (reprint author), NIAAA, Lab Neuroimaging, Bethesda, MD USA. NR 41 TC 4 Z9 4 U1 0 U2 2 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2008 VL 31 IS 3 BP 233 EP 237 PG 5 WC Substance Abuse SC Substance Abuse GA 374TL UT WOS:000261066500005 PM 23584865 ER PT J AU Tidey, JW Monti, PM Rohsenow, DJ Gwaltney, CJ Miranda, R McGeary, JE MacKillop, J Swift, RM Abrams, DB Shiffman, S Paty, JA AF Tidey, Jennifer W. Monti, Peter M. Rohsenow, Damaris J. Gwaltney, Chad J. Miranda, Robert, Jr. McGeary, John E. MacKillop, James Swift, Robert M. Abrams, David B. Shiffman, Saul Paty, Jean A. TI Moderators of naltrexone's effects on drinking, urge, and alcohol effects in non-treatment-seeking heavy drinkers in the natural environment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE naltrexone; family history; genetics; treatment; pharmacology ID OPIOID RECEPTOR GENE; NATIONAL-COMORBIDITY-SURVEY; DRD4 VNTR POLYMORPHISM; FAMILY-HISTORY; SOCIAL DRINKERS; DEPENDENCE; CONSUMPTION; EFFICACY; PHARMACOTHERAPY; METAANALYSIS AB Background: Naltrexone (NTX) has proven to be effective with alcoholics in treatment, with most controlled clinical trials showing beneficial effects on heavy drinking rates. However, little is known about the behavioral mechanisms underlying the effects of NTX on drinking, or about patient characteristics that may moderate NTX's effects on drinking. In this study, ecological momentary assessment (EMA) techniques were used to investigate some of the putative mechanisms of naltrexone's effects on drinking in heavy drinkers who were not seeking treatment for alcohol problems. Polymorphisms in the D4 dopamine receptor (DRD4) gene and the mu-opiate receptor (OPRM1) gene, family history of alcohol problems, age of onset of alcoholism and gender were explored as potential moderators of NTX's effects. Methods: After a 1-week placebo lead-in period, heavy drinkers (n = 180), 63% of whom were alcohol-dependent, were randomized to 3 weeks of daily naltrexone (50 mg) or placebo. Throughout the study, participants used EMA on palm-pilot computers to enter, in real time, drink data, urge levels, and subjective effects of alcohol consumption. Results: Naltrexone reduced percentage drinking days in all participants and reduced percent heavy drinking days in DRD4-L individuals; NTX decreased urge levels in participants with younger age of alcoholism onset; NTX increased time between drinks in participants who had more relatives with alcohol problems; and NTX reduced the stimulating effects of alcohol in women. OPRM1 status did not moderate any of NTX's effects. Conclusions: These results confirm earlier findings of NTX's effects on drinking and related subjective effects, and extend them by describing individual difference variables that moderate these effects in the natural environment, using data collected in real time. C1 [Tidey, Jennifer W.; Monti, Peter M.; Rohsenow, Damaris J.; Gwaltney, Chad J.; Miranda, Robert, Jr.; McGeary, John E.; MacKillop, James; Swift, Robert M.; Abrams, David B.; Shiffman, Saul; Paty, Jean A.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Tidey, Jennifer W.; Monti, Peter M.; Rohsenow, Damaris J.; Gwaltney, Chad J.; Miranda, Robert, Jr.; McGeary, John E.; MacKillop, James; Swift, Robert M.; Abrams, David B.; Shiffman, Saul; Paty, Jean A.] Brown Univ, Vet Affairs Med Ctr, Providence, RI 02912 USA. [Tidey, Jennifer W.; Monti, Peter M.; Rohsenow, Damaris J.; Gwaltney, Chad J.; Miranda, Robert, Jr.; McGeary, John E.; MacKillop, James; Swift, Robert M.; Abrams, David B.; Shiffman, Saul; Paty, Jean A.] NIH, OBSSR, Bethesda, MD 20892 USA. [Tidey, Jennifer W.; Monti, Peter M.; Rohsenow, Damaris J.; Gwaltney, Chad J.; Miranda, Robert, Jr.; McGeary, John E.; MacKillop, James; Swift, Robert M.; Abrams, David B.; Shiffman, Saul; Paty, Jean A.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA USA. RP Tidey, JW (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box G S121-5, Providence, RI 02912 USA. EM jennifer_tidey@brown.edu RI Shiffman, Saul/K-7337-2012 FU NIAAA NIH HHS [1K23 AA014966, 2R01 AA07850, K23 AA014966, K23 AA014966-01, R01 AA007850, R01 AA007850-11A1, T32 AA007459, T32 AA007459-15, T32 AA07459] NR 56 TC 76 Z9 77 U1 4 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2008 VL 32 IS 1 BP 58 EP 66 DI 10.1111/j.1530-0277.2007.00545.x PG 9 WC Substance Abuse SC Substance Abuse GA 242ZE UT WOS:000251763900012 PM 18028530 ER PT J AU Bousquet, J Khaltaev, N Cruz, AA Denburg, J Fokkens, WJ Togias, A Zuberbier, T Baena-Cagnani, CE Canonica, GW van Weel, C Agache, I Ait-Khaled, N Bachert, C Blaiss, MS Bonini, S Boulet, LP Bousquet, PJ Camargos, P Carlsen, KH Chen, Y Custovic, A Dahl, R Demoly, P Douagui, H Durham, SR van Wijk, RG Kalayci, O Kaliner, MA Kim, YY Kowalski, ML Kuna, P Le, LTT Lemiere, C Li, J Lockey, RF Mavale-Manuel, S Meltzer, EO Mohammad, Y Mullol, J Naclerio, R Hehir, REO Ohta, K Ouedraogo, S Palkonen, S Papadopoulos, N Passalacqua, G Pawankar, R Popov, TA Rabe, KF Rosado-Pinto, J Scadding, GK Simons, FER Toskala, E Valovirta, E van Cauwenberge, P Wang, DY Wickman, M Yawn, BP Yorgancioglu, A Yusuf, OM Zar, H Annesi-Maesano, I Bateman, ED Ben Kheder, A Boakye, DA Bouchard, J Burney, P Busse, WW Chan-Yeung, M Chavannes, NH Chuchalin, A Dolen, WK Emuzyte, R Grouse, L Humbert, M Jackson, C Johnston, SL Keith, PK Kemp, JP Klossek, JM Larenas-Linnemann, D Lipworth, B Malo, JL Marshall, GD Naspitz, C Nekam, K Niggemann, B Nizankowska-Mogilnicka, E Okamoto, Y Orru, MP Potter, P Price, D Stoloff, SW Vandenplas, O Viegi, G Williams, D AF Bousquet, J. Khaltaev, N. Cruz, A. A. Denburg, J. Fokkens, W. J. Togias, A. Zuberbier, T. Baena-Cagnani, C. E. Canonica, G. W. van Weel, C. Agache, I. Ait-Khaled, N. Bachert, C. Blaiss, M. S. Bonini, S. Boulet, L. -P. Bousquet, P. -J. Camargos, P. Carlsen, K. -H. Chen, Y. Custovic, A. Dahl, R. Demoly, P. Douagui, H. Durham, S. R. van Wijk, R. Gerth Kalayci, O. Kaliner, M. A. Kim, Y. -Y. Kowalski, M. L. Kuna, P. Le, L. T. T. Lemiere, C. Li, J. Lockey, R. F. Mavale-Manuel, S. Meltzer, E. O. Mohammad, Y. Mullol, J. Naclerio, R. Hehir, R. E. O. Ohta, K. Ouedraogo, S. Palkonen, S. Papadopoulos, N. Passalacqua, G. Pawankar, R. Popov, T. A. Rabe, K. F. Rosado-Pinto, J. Scadding, G. K. Simons, F. E. R. Toskala, E. Valovirta, E. van Cauwenberge, P. Wang, D. -Y. Wickman, M. Yawn, B. P. Yorgancioglu, A. Yusuf, O. M. Zar, H. Annesi-Maesano, I. Bateman, E. D. Ben Kheder, A. Boakye, D. A. Bouchard, J. Burney, P. Busse, W. W. Chan-Yeung, M. Chavannes, N. H. Chuchalin, A. Dolen, W. K. Emuzyte, R. Grouse, L. Humbert, M. Jackson, C. Johnston, S. L. Keith, P. K. Kemp, J. P. Klossek, J. -M. Larenas-Linnemann, D. Lipworth, B. Malo, J. -L. Marshall, G. D. Naspitz, C. Nekam, K. Niggemann, B. Nizankowska-Mogilnicka, E. Okamoto, Y. Orru, M. P. Potter, P. Price, D. Stoloff, S. W. Vandenplas, O. Viegi, G. Williams, D. TI Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen) SO ALLERGY LA English DT Review DE ARIA; asthma; guideline; management; rhinitis ID QUALITY-OF-LIFE; HOUSE-DUST-MITE; AQUEOUS NASAL SPRAY; PLACEBO-CONTROLLED TRIAL; SKIN-TEST REACTIVITY; COMMUNITY-RESPIRATORY-HEALTH; RANDOMIZED CONTROLLED-TRIAL; INTRANASAL FLUTICASONE PROPIONATE; NATURAL-RUBBER LATEX; LABORATORY-ANIMAL ALLERGY AB Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients. C1 [Bousquet, J.] Univ Hosp, Montpellier, France. [Demoly, P.] Hop Arnaud Villeneuve, INSERM, Univ Hosp Montpellier, U657, Montpellier, France. [Khaltaev, N.] GARD ARIA, Geneva, Switzerland. [Cruz, A. A.] Univ Fed Bahia, Sch Med, BR-41170290 Salvador, BA, Brazil. [Denburg, J.] McMaster Univ, AllerGen NCE, Hamilton, ON L8S 4L8, Canada. [Fokkens, W. J.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Togias, A.] NIAID, Bethesda, MD 20892 USA. [Zuberbier, T.] Charite, Allergy Ctr Charite, D-13353 Berlin, Germany. [Baena-Cagnani, C. E.] WAO, Cordoba, Argentina. [Baena-Cagnani, C. E.] Catholic Univ Cordoba, Cordoba, Argentina. [Canonica, G. W.] Univ Genoa, Allergy & Resp Dis Clin, Genoa, Italy. [van Weel, C.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Agache, I.] Transylvania Univ, Brasov, Romania. [Bachert, C.] Univ Hosp Ghent, UZG, Ghent, Belgium. [Blaiss, M. S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Bonini, S.] Univ Naples 2, INMM CNR, Rome, Italy. [Boulet, L. -P.] Hop Laval, Inst Cardiol & Pneumol, Quebec City, PQ, Canada. [Boulet, L. -P.] Univ Laval, Quebec City, PQ, Canada. [Bousquet, P. -J.] Univ Nimes Hosp, F-30006 Nimes, France. [Camargos, P.] Univ Fed Minas Gerais, Univ Hosp, Sch Med, Belo Horizonte, MG, Brazil. [Carlsen, K. -H.] Univ Oslo, Rikshosp, Norwegian Sch Sport Sci, Fac Med, N-0027 Oslo, Norway. [Chen, Y.] Capital Inst Pediat, Asthma Clin & Educ Ctr, Natl Cooperat Grp Pediat Res Asthma, Beijing, Peoples R China. [Custovic, A.] Univ Manchester, Manchester, Lancs, England. [Dahl, R.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Douagui, H.] Ctr Hosp Univ Beni Messous, Algiers, Algeria. [Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, London, England. [van Wijk, R. Gerth] Erasmus MC, Rotterdam, Netherlands. [Kalayci, O.] Pediat Allergy & Asthma Unit, Ankara, Turkey. [Kaliner, M. A.] Geo Washington Univ, Sch Med, Washington, DC USA. [Kaliner, M. A.] Inst Asthma & Allergy, Chevy Chase, MD USA. [Kim, Y. -Y.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Kuna, P.] Med Univ Lodz, Barlicki Univ Hosp, Lodz, Poland. [Le, L. T. T.] Univ Med & Pharm, Ho Chi Minh City, Vietnam. [Lemiere, C.; Malo, J. -L.] Univ Montreal, Montreal, PQ, Canada. [Li, J.] First Affiliated Hosp, Guangzhou Med Sch, Guangzhou Inst Resp Dis, Guangzhou, Peoples R China. [Lockey, R. F.] Univ S Florida, Coll Med, Tampa, FL 33620 USA. [Mavale-Manuel, S.] Childrens Hosp, Maputo, Mozambique. [Meltzer, E. O.] Univ Calif San Diego, Allergy & Asthma Med Grp & Res Ctr, San Diego, CA 92103 USA. [Mohammad, Y.] Tishreen Univ Sch Med, Latakia, Syria. [Mullol, J.] Hosp Clin IDIBAPS, Barcelona, Catalonia, Spain. [Naclerio, R.] Univ Chicago, Chicago, IL 60637 USA. [Hehir, R. E. O.] Alfred Hosp, Melbourne, Vic, Australia. [Hehir, R. E. O.] Monash Univ, Melbourne, Vic 3004, Australia. [Ohta, K.] Teikyo Univ, Sch Med, Tokyo 173, Japan. [Ouedraogo, S.] Ctr Hosp Univ Pediat Charles de Gaulle, Ouagadougou, Burkina Faso. [Palkonen, S.] EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium. [Papadopoulos, N.] Univ Athens, Allergy Res Ctr, Athens, Greece. [Passalacqua, G.] Univ Genoa, Genoa, Italy. [Pawankar, R.] Nippon Med Sch, Bunkyo Ku, Tokyo 113, Japan. [Popov, T. A.] Med Univ Sofia, Clin Allergy & Asthma, Sofia, Bulgaria. [Rabe, K. F.; Chavannes, N. H.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Rosado-Pinto, J.] Hosp Dona Estefania, Lisbon, Portugal. [Scadding, G. K.] UCL, Royal Natl TNE Hosp London, London, England. [Simons, F. E. R.] Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. [Toskala, E.] Helsinki Univ Hosp, Helsinki, Finland. [Toskala, E.] Finnish Inst Occupat Hlth, Helsinki, Finland. [Valovirta, E.] Turku Allergy Ctr, Turku, Finland. [van Cauwenberge, P.] Univ Ghent, B-9000 Ghent, Belgium. [Wang, D. -Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117548, Singapore. [Wickman, M.] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden. [Wickman, M.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Yawn, B. P.] Univ Minnesota, Olmsted Med Ctr, Rochester, MN USA. [Yorgancioglu, A.] Celal Bayar Univ, Sch Med, Manisa, Turkey. [Yusuf, O. M.] Allergy & Asthma Inst, Islamabad, Pakistan. [Zar, H.] Univ Cape Town, Sch Child & Adolescent Hlth, Red Cross Childrens Hosp, ZA-7925 Cape Town, South Africa. [Annesi-Maesano, I.] INSERM, EPAR U707, F-75654 Paris 13, France. [Annesi-Maesano, I.] UPMC, EPAR, UMR S, Paris, France. [Bateman, E. D.] Univ Cape Town, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. [Ben Kheder, A.] Univ Tunis, Tunisian Soc Resp Dis, Pan African Thorac Soc, Tunis, Tunisia. [Boakye, D. A.] Univ Ghana, Coll Hlth Sci, Noguchi Mem Inst Med Res, Legon, Accra, Ghana. [Bouchard, J.] Hop Malbaie, Quebec City, PQ, Canada. [Burney, P.; Johnston, S. L.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Busse, W. W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA. [Chan-Yeung, M.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Chuchalin, A.] Pulmonol Res Inst, Moscow, Russia. [Chuchalin, A.] Russian Resp Soc, Moscow, Russia. [Dolen, W. K.] Med Coll Georgia, Augusta, GA 30912 USA. [Emuzyte, R.] Vilnius State Univ, Fac Med, Vilnius, Lithuania. [Grouse, L.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Humbert, M.] Univ Paris Sud, Hop Antoine Beclere, Clamart, France. [Jackson, C.] Univ Dundee, Tayside Ctr Gen Practice, Dundee, Scotland. [Keith, P. K.] McMaster Univ, Hamilton, ON, Canada. [Kemp, J. P.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Klossek, J. -M.] Univ Poitiers, Poitiers, France. [Larenas-Linnemann, D.] Hosp Med Sur, Mexico City, DF, Mexico. [Malo, J. -L.] Hop Sacre Coeur Montreal, Montreal, PQ, Canada. [Marshall, G. D.] Univ Mississippi, Jackson, MS 39216 USA. [Naspitz, C.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Nekam, K.] Hosp Hospitaller Bros Buda, Budapest, Hungary. [Niggemann, B.] German Red Cross Hosp Berlin, Berlin, Germany. [Nizankowska-Mogilnicka, E.] Jagiellonian Univ, Sch Med, Krakow, Poland. [Okamoto, Y.] Chiba Univ, Chiba, Japan. [Potter, P.] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Potter, P.] Univ Cape Town, Lung Inst, ZA-7700 Rondebosch, South Africa. [Price, D.] Univ Aberdeen, Aberdeen, Scotland. [Stoloff, S. W.] Univ Nevada, Sch Med, Reno, NV 89557 USA. [Vandenplas, O.] Catholic Univ Louvain, Univ Hosp Mt Godinne, Yvoir, Belgium. [Viegi, G.] CNR, Inst Clin Physiol, I-56100 Pisa, Italy. [Williams, D.] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27515 USA. RP Bousquet, J (reprint author), Univ Hosp, Montpellier, France. RI O'Hehir, Robyn/H-3627-2011; Chavannes, Niels/F-1148-2011; Johnston, Sebastian/I-2423-2012; Dahl, Ronahl/F-8170-2013; jackson, cathy/H-4869-2013; Custovic, Adnan/A-2435-2012; Annesi-Maesano, Isabella/D-9173-2016; van Weel, Chris/D-4375-2009; Cruz, Alvaro/I-1676-2012 OI O'Hehir, Robyn/0000-0002-3489-7595; Popov, Todor/0000-0001-5052-5866; Price, David/0000-0002-9728-9992; Papadopoulos, Nikolaos/0000-0002-2508-3872; Bousquet, Philippe Jean/0000-0002-0217-5483; Chavannes, Niels/0000-0002-8607-9199; Bonini, Sergio/0000-0003-0079-3031; Custovic, Adnan/0000-0001-5218-7071; van Weel, Chris/0000-0003-3653-4701; Cruz, Alvaro/0000-0002-7403-3871 NR 2256 TC 1650 Z9 1894 U1 56 U2 326 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PY 2008 VL 63 SU 86 BP 8 EP + DI 10.1111/j.1398-9995.2007.01620.x PG 154 WC Allergy; Immunology SC Allergy; Immunology GA 271YZ UT WOS:000253825900001 PM 18331513 ER PT J AU Wilson, T Maric, I Wu, Y Fu, W Stoddard, J Noel, P Robyn, J Metcalfe, D AF Wilson, T. Maric, I Wu, Y. Fu, W. Stoddard, J. Noel, P. Robyn, J. Metcalfe, D. TI Activating NRAS and JAK2 mutations associated with KIT D816V positive systemic mastocytosis SO ALLERGY LA English DT Meeting Abstract CT 27th Congress of the European-Academy-of-Allergology-and-Clinical-Immunology CY JUN 07-11, 2008 CL Barcelona, SPAIN SP European Acad Allergol & Clinical Immunol C1 [Wilson, T.; Wu, Y.; Robyn, J.; Metcalfe, D.] NIAID, Natl Inst Hlth, Lab Allerg Dis, Bethesda, MD 20892 USA. [Maric, I; Fu, W.; Stoddard, J.; Noel, P.] Natl Inst Hlth, Ctr Clin, Dept Lab Med, 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 0105-4538 J9 ALLERGY JI Allergy PY 2008 VL 63 SU 88 MA 33 BP 15 EP 16 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 306GF UT WOS:000256235600033 ER PT J AU Swindle, E Deleo, F Metcalfe, D AF Swindle, E. DeLeo, F. Metcalfe, D. TI IFN gamma enhances the anti-bacterial and pro-inflammatory response of human mast cells to Staphylococcus aureus SO ALLERGY LA English DT Meeting Abstract CT 27th Congress of the European-Academy-of-Allergology-and-Clinical-Immunology CY JUN 07-11, 2008 CL Barcelona, SPAIN SP European Acad Allergol & Clinical Immunol C1 [Swindle, E.; Metcalfe, D.] NIAID, Allerg Dis Res Lab, NIH, Bethesda, MD 20892 USA. [DeLeo, F.] NIAID, RML, NIH, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-4538 J9 ALLERGY JI Allergy PY 2008 VL 63 SU 88 MA 63 BP 29 EP 30 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 306GF UT WOS:000256235600063 ER PT J AU Simons, FER Frew, AJ Ansotegui, IJ Bochner, BS Golden, DBK Finkelman, FD Leung, DYM Lotvall, J Marone, G Metcalfe, DD Muller, U Rosenwasser, LJ Sampson, HA Schwartz, LB van Hage, M Walls, AF AF Simons, F. E. R. Frew, A. J. Ansotegui, I. J. Bochner, B. S. Golden, D. B. K. Finkelman, F. D. Leung, D. Y. M. Lotvall, J. Marone, G. Metcalfe, D. D. Mueller, U. Rosenwasser, L. J. Sampson, H. A. Schwartz, L. B. van Hage, M. Walls, A. F. TI Practical allergy (PRACTALL) report: risk assessment in anaphylaxis SO ALLERGY LA English DT Review DE allergen skin test; allergen-specific IgE; anaphylaxis; food allergy; insect venom allergy; tryptase AB Effector mechanisms in anaphylaxis were reviewed. Current approaches to confirmation of the clinical diagnosis were discussed. Improved methods for distinguishing between allergen sensitization (which is common in the general population) and clinical risk of anaphylaxis (which is uncommon) were deliberated. Innovative techniques that will improve risk assessment in anaphylaxis in the future were described. C1 Univ Manitoba, Dept Immunol, Dept Pediat & Child Hlth, Winnipeg, MB R3A 1R9, Canada. Brighton Gen Hosp, Dept Resp Med, Brighton, E Sussex, England. Royal Hosp, Belfast, Antrim, North Ireland. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Cincinnati, Coll Med, Div Immunol, Cincinnati, OH USA. Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO USA. Dept Resp Med & Allergol, Gothenburg, Sweden. Univ Naples Federico 2, Div Clin Immunol & Allergy, Naples, Italy. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Med Klin, Bern, Switzerland. Childrens Mercy Hosp & Clin, Dept Pediat, Kansas City, MO 64108 USA. Mt Sinai Sch Med, Dept Pediat & Biomed Sci, New York, NY USA. Virginia Commonwealth Univ, Div Rheumatol Allergy & Immunol, Richmond, VA USA. Karolinska Inst, Dept Med Clin Immunol & Allergy, Stockholm, Sweden. St Gorans Univ Hosp, S-11281 Stockholm, Sweden. Southampton Gen Hosp, Immunopharmacol Grp, Southampton SO9 4XY, Hants, England. RP Simons, FER (reprint author), Univ Manitoba, Dept Immunol, Dept Pediat & Child Hlth, 820 Sherbrook St, Winnipeg, MB R3A 1R9, Canada. RI van Hage, Marianne/A-9678-2017 OI van Hage, Marianne/0000-0003-3091-1596 FU Department of Health [H039]; Intramural NIH HHS; Medical Research Council [G0500729] NR 1 TC 13 Z9 15 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-4538 J9 ALLERGY JI Allergy PD JAN PY 2008 VL 63 IS 1 BP 35 EP 37 DI 10.1111/j.1398-9995.2007.01605.x PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 236UA UT WOS:000251327700003 PM 18053014 ER PT J AU Masjedi, K Minang, J Hindsen, M Bruze, M Ahlborg, N AF Masjedi, K. Minang, J. Hindsen, M. Bruze, M. Ahlborg, N. TI Relationship between fluctuations in the systemic T-cell reactivity to nickel and variability of nickel patch test reactivity over time SO ALLERGY LA English DT Meeting Abstract CT 27th Congress of the European-Academy-of-Allergology-and-Clinical-Immunology CY JUN 07-11, 2008 CL Barcelona, SPAIN SP European Acad Allergol & Clinical Immunol C1 [Masjedi, K.; Ahlborg, N.] Mabtech, Res & Dev, Nacka Strand, Sweden. NCI, AIDS Vaccine Program, Frederick, MD 21701 USA. [Hindsen, M.; Bruze, M.] Malmo Univ Hosp, Dept Occupat & Environm Dermatol, Malmo, Sweden. 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 0105-4538 J9 ALLERGY JI Allergy PY 2008 VL 63 SU 88 MA 101 BP 48 EP 48 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 306GF UT WOS:000256235600101 ER PT J AU Carter, M Uzzaman, A Scott, L Quezado, Z Metcalfe, D AF Carter, M. Uzzaman, A. Scott, L. Quezado, Z. Metcalfe, D. TI Pediatric mastocytosis: routine anesthetic management for a complex disease SO ALLERGY LA English DT Meeting Abstract CT 27th Congress of the European-Academy-of-Allergology-and-Clinical-Immunology CY JUN 07-11, 2008 CL Barcelona, SPAIN SP European Acad Allergol & Clinical Immunol C1 [Carter, M.; Uzzaman, A.; Scott, L.] NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. [Quezado, Z.; Metcalfe, D.] NIH, Dept Anesthesia & Surg Serv, Bethesda, MD 20892 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 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 0105-4538 J9 ALLERGY JI Allergy PY 2008 VL 63 SU 88 MA 957 BP 354 EP 354 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 306GF UT WOS:000256235600943 ER PT J AU Jarvik, L Larue, A Blacker, D Gatz, M Kawas, C McArdle, JJ Morris, JC Mortimer, JA Ringman, JM Ercoli, L Freimer, N Gokhman, I Manly, JJ Plassman, BL Rasgon, N Roberts, JS Sunderland, T Swan, GE Wolf, PA Zonderman, AB AF Jarvik, Lissy LaRue, Asenath Blacker, Deborah Gatz, Margaret Kawas, Claudia McArdle, John J. Morris, John C. Mortimer, James A. Ringman, John M. Ercoli, Linda Freimer, Nelson Gokhman, Izabella Manly, Jennifer J. Plassman, Brenda L. Rasgon, Natalie Roberts, Jeffrey Scott Sunderland, Trey Swan, Gary E. Wolf, Phillip A. Zonderman, Alan B. TI Children of persons with Alzheimer disease - What does the future hold? SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Review DE Alzheimer disease offspring; risk factors ID APOLIPOPROTEIN-E GENOTYPE; MILD COGNITIVE IMPAIRMENT; ELDERLY AFRICAN-AMERICANS; OLDER MEXICAN-AMERICANS; POPULATION-BASED COHORT; APOE EPSILON-4 ALLELE; MIDDLE-AGED CHILDREN; CEREBROSPINAL-FLUID; GENETIC RISK; DIABETES-MELLITUS AB Children of persons with Alzheimer disease (AD), as a group, face an increased risk of developing AD. Many of them, throughout their adult lives, seek input on how to reduce their chances of one day suffering their parent's fate. We examine the state of knowledge with respect to risk and protective factors for AD and recommend a research agenda with special emphasis on AD offspring. C1 [Jarvik, Lissy; Ercoli, Linda; Freimer, Nelson] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Ringman, John M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Ringman, John M.] Univ Calif Los Angeles, Alzheimers Dis Res Ctr, Los Angeles, CA 90024 USA. [LaRue, Asenath] VA Greater Los Angeles Hlth Care Syst, Dept Vet Affairs, Los Angeles, CA USA. [Jarvik, Lissy; Ercoli, Linda; Freimer, Nelson] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Gatz, Margaret; McArdle, John J.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Kawas, Claudia] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Kawas, Claudia] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92717 USA. [Gokhman, Izabella] S Bay Mental Hlth Ctr, Dept Mental Hlth, Hawthorne, CA USA. [Rasgon, Natalie] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Swan, Gary E.] SRI Int, Hlth Sci Ctr, Menlo Pk, CA 94025 USA. [LaRue, Asenath] Univ Wisconsin, Wisconsin Alzheimers Inst, Dept Med, Madison, WI USA. [Blacker, Deborah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wolf, Phillip A.] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA. [Morris, John C.] Washington Univ, Sch Med, St Louis, MO USA. [Mortimer, James A.] Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, MDC, Tampa, FL USA. [Manly, Jennifer J.] Columbia Univ, GH Sergievsky Ctr, New York, NY USA. [Manly, Jennifer J.] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Ctr, New York, NY USA. [Plassman, Brenda L.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Roberts, Jeffrey Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Jarvik, L (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, 760 Westwood Plaza, Los Angeles, CA 90095 USA. EM ljarvik@ucla.edu RI Morris, John/A-1686-2012; OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS; NHGRI NIH HHS [R01 HG002213]; NHLBI NIH HHS [HL51429]; NIA NIH HHS [5R01 AG08122, 5R01 AG16495, AG08549, K08 AG022228, K08AG-22228, P01 AG-1657, P01 AG026276, P50 AG005134, P50 AG016573, P50 AG16573, R01 AG008122, R01 AG008549, R01 AG016495, R01 AG021055, R01 AG08724, R01 HG/AG 02213]; PHS HHS [5 P50 AGO5134, G09341] NR 202 TC 15 Z9 15 U1 7 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2008 VL 22 IS 1 BP 6 EP 20 PG 15 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 270DK UT WOS:000253700000003 PM 18317242 ER PT J AU Hodes, RJ Buckholtz, N Cahan, V Morrison-Bogorad, M AF Hodes, Richard J. Buckholtz, Neil Cahan, Vicky Morrison-Bogorad, Marcelle TI Eyes on the prize: Federal Alzheimer's research effort aims to facilitate interventions SO ALZHEIMERS & DEMENTIA LA English DT Article; Proceedings Paper CT Leon Thal Symposium on the Prevention of Dementia CY DEC 02-04, 2007 CL Las Vegas, NV SP Lou Ruvo Brain Inst DE Alzheimer's disease; national institute on aging; dementia ID MILD COGNITIVE IMPAIRMENT; FACTOR GENE-THERAPY; NEURODEGENERATIVE DISEASE; INCIDENT DEMENTIA; TRANSGENIC MODEL; OLDER PERSONS; A-BETA; BRAIN; EXERCISE; MEMORY AB The public Alzheimer's disease (AD) research enterprise began in earnest in the mid-1970s with the creation by Congress of the National Institute on Aging at the National Institutes of Health. Today, AD research is a maturing field of study, with federal effort seeking to encourage the creativity and insights of individual investigators, and targeting special areas for emphasis. It is inspired by the legacy of our friend and colleague Leon Thai, whose innovative and collaborative approach to scientific research serves as a guidepost as we move toward the discovery of new and effective ways to prevent AD or slow its progression. This article describes the progress to date and potentially promising areas of study from the vantage point of the National Institute on Aging. (c) 2008 The Alzheimer's Association. All rights reserved. C1 [Hodes, Richard J.; Buckholtz, Neil; Cahan, Vicky; Morrison-Bogorad, Marcelle] US Dept Hlth & Human Serv, Natl Inst Hlth, NIA, Bethesda, MD USA. RP Cahan, V (reprint author), US Dept Hlth & Human Serv, Natl Inst Hlth, NIA, Bethesda, MD USA. EM cahanv@nia.nih.gov FU NIA NIH HHS [U19 AG010483] NR 46 TC 4 Z9 4 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2008 VL 4 IS 1 SU 1 BP S37 EP S47 DI 10.1016/j.jalz.2007.11.002 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 256AI UT WOS:000252699700008 PM 18631998 ER PT J AU Cairns, JA Wittes, J Wyse, DG Pogue, J Gent, M Hirsh, J Marler, J Pritchett, ELC AF Cairns, John A. Wittes, Janet Wyse, D. George Pogue, Janet Gent, Michael Hirsh, Jack Marler, John Pritchett, Edward L. C. TI Monitoring the ACTIVE-W trial: Some issues in monitoring a noninferiority trial SO AMERICAN HEART JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; NON-INFERIORITY AB Noninferiority comparisons of new to current therapies and the use of composite outcomes represent significant advances in the design of clinical trials. They increasingly characterize trials of new. cardiovascular agents, posing new challenges to Data Safety Monitoring Boards (DSMB) and principal investigators. The ACTIVE-W study was a noninferiority comparison of the combination of clopidogrel and acetylsalicylic acid versus oral anticoagulant among patients with atrial fibrillation. When unexpectedly high rates of stroke and then of the composite outcome of stroke, non-central nervous system systemic embolism, myocardial infarction, and vascular death emerged, the DSMB modified its monitoring plan and conducted its first formal interim analysis much earlier than had been planned in the DSMB charter. The study was terminated when only 27% of the anticipated outcomes had occurred. This paper discusses issues of appropriate stopping guidelines for noninferiority trials and the early emergence of significant harm in relation to one component (stroke) of a composite outcome. Conditional power was not determined concurrently with the HRs during the monitoring of ACTIVE-W; however, the members of the DSMB now believe that such calculations should be considered as useful adjuncts to the calculation of HRs and could lead to earlier termination of. noninferiority trials whose interim results suggest futility, without the need for convincing proof of harm. C1 [Cairns, John A.] Univ British Columbia, GLD Hlth Care Ctr, Vancouver, BC V5Z 1M9, Canada. [Wittes, Janet] Stat Collaborat Inc, Washington, DC USA. [Wyse, D. George] Libin Cardiovasc Inst Alberta, Calgary, AB, Canada. [Pogue, Janet; Gent, Michael; Hirsh, Jack] McMaster Univ, Hamilton, ON, Canada. [Marler, John] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Pritchett, Edward L. C.] Duke Univ, Durham, NC USA. RP Cairns, JA (reprint author), Univ British Columbia, GLD Hlth Care Ctr, 2775 Laurel St,Rm 9113, Vancouver, BC V5Z 1M9, Canada. EM jacairns@medd.med.ubc.ca NR 18 TC 5 Z9 5 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2008 VL 155 IS 1 BP 33 EP 41 DI 10.1016/j.ahj.2007.09.011 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242NO UT WOS:000251732400006 PM 18082486 ER PT J AU Deo, R Fyr, CLW Fried, LF Newman, AB Harris, TB Angleman, S Green, C Kritchevsky, SB Chertow, GM Cummings, SR Shlipak, MG AF Deo, Rajat Fyr, Christina L. Wassel Fried, Linda F. Newman, Anne B. Harris, Tamara B. Angleman, Sara Green, Christie Kritchevsky, Stephen B. Chertow, Glenn M. Cummings, Steven R. Shlipak, Michael G. CA Hlth ABC Study TI Kidney dysfunction and fatal cardiovascular disease - an association independent of atherosclerotic events: Results from the Health, Aging, and Body Composition (Health ABC) study SO AMERICAN HEART JOURNAL LA English DT Article ID GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; RENAL-INSUFFICIENCY; CLINICAL EVALUATION; ELDERLY PERSONS; MORTALITY RISK; MARKER; CREATININE; PREDICTOR; PLASMA AB Background Impaired kidney function has been associated with increased risk for death, myocardial infarction, stroke, and heart failure in high-risk populations. We evaluated whether impaired kidney function predicted risk of fatal cardiovascular disease independent of prevalent and incident cardiovascular events. Methods The Health, Aging, and Body Composition study is a cohort of well-functioning, elderly participants aged 70 to 79 years at entry. We measured serum cystatin C and creatinine from baseline plasma samples of 3044 participants and followed them over 6 years, examining the associations among kidney function, cardiovascular death,. and incident cardiovascular events. Cystatin C was categorized as low (< 0.84 mg/L), medium (0.84-1.18 mg/L), or high (>= 1.19 mg/L); serum creatinine (cutoff value of >= 1.3 in women and >= 1.5 in men) and estimated glomerular filtration rate (eGFR; greater and less than 60 mL/min per 1.73 m(2)) were dichotomized. Results During follow-up, 242 cardiovascular deaths occurred, of which 69 were in participants without prior cardiovascular events; 294 incident cardiovascular events occurred including 135 myocardial infarctions and 163 strokes. Higher cystatin C concentrations were significantly associated with cardiovascular death (adjusted hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.05-2.76 for the medium cystatin C group; and HR 2.24, 95% CI 1.30-3.86 for the high cystatin C group, relative to the low cystatin C group). The point estimate was of greater magnitude in the analysis that excluded prevalent cardiovascular disease (adjusted HR 2.68, 95% CI 0.94-7.70 for the medium cystatin C group; and HR 4.91, 95% CI, 1.55-15.54 for the high cystatin C group). Elevated creatinine levels (adjusted HR 1.54, 95% CI 1.02-2.33, and HR 2.28, 95% CI 1.10-4.73 among participants without a history of cardiovascular disease) were also associated with cardiovascular death. No significant association was found between low eGFR and cardiovascular death. In addition, cystatin C, low eGFR, or elevated creatinine levels were not associated with other cardiovascular events. Conclusion Impaired kidney function is a strong predictor of cardiovascular death, particularly among participants without prior history of cardiovascular disease. C1 [Shlipak, Michael G.] Univ Calif San Francisco, Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, J Paul Sticht Ctr Aging & Rehabil, Winston Salem, NC USA. [Green, Christie] Univ Tennessee, Dept Med, Div Nephrol, Memphis, TN 38104 USA. [Harris, Tamara B.; Angleman, Sara] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Fried, Linda F.] VA Pittsburgh Hlth Care Syst, Renal Sect, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Fyr, Christina L. Wassel; Chertow, Glenn M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Fyr, Christina L. Wassel; Chertow, Glenn M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Deo, Rajat] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, VA Med Ctr 111A1, Gen Internal Med Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM Michael.Shlipak@ucsf.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Angleman, Sara/0000-0002-9520-5716; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 17 TC 59 Z9 66 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2008 VL 155 IS 1 BP 62 EP 68 DI 10.1016/j.ahj.2007.08.012 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242NO UT WOS:000251732400010 PM 18082491 ER PT J AU Miller, FG Truog, RD AF Miller, Franklin G. Truog, Robert D. TI An apology for socratic bioethics SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE socratic bioethics; hybrid discipline ID BRAIN-DEATH; CARDIAC DEATH; ORGAN-TRANSPLANTATION; CLINICAL-TRIALS; EQUIPOISE; DONATION; ABANDON; ETHICS AB Bioethics is a hybrid discipline. As a theoretical enterprise it stands for untrammeled inquiry and argument. Yet it aims to influence medical practice and policy. In this article we explore tensions between these two dimensions of bioethics and examine the merits and perils of a Socratic approach to bioethics that challenges the conventional wisdom. C1 [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Truog, Robert D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Cambridge, MA 02138 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 16 TC 4 Z9 4 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 7 BP 3 EP 7 DI 10.1080/15265160802248153 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 342UF UT WOS:000258808400003 PM 18759171 ER PT J AU Grady, C Danis, M Soeken, KL O'Donnell, P Taylor, C Farrar, A Ulrich, CM AF Grady, Christine Danis, Marion Soeken, Karen L. O'Donnell, Patricia Taylor, Carol Farrar, Adrienne Ulrich, Connie M. TI Does ethics education influence the moral action of practicing nurses and social workers? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE ethics education; moral action; ethics consultation ID HEALTH-CARE; DECISION-MAKING; DILEMMAS; DISTRESS; STUDENTS; NEEDS AB Purpose/methods: This study investigated the relationship between ethics education and training, and the use and usefulness of ethics resources, confidence in moral decisions, and moral action/activism through a survey of practicing nurses and social workers from four United States (US) census regions. Findings: The sample (n = 1215) was primarily Caucasian (83%), female (85%), well educated (57% with a master's degree). no ethics education at all was reported by 14% of study participants (8% of social workers had no ethics education, versus 23% of nurses), and only 57% of participants had ethics education in their professional educational program. Those with both professional ethics education and in-service or continuing education were more confident in their moral judgments and more likely to use ethics resources and to take moral action. Social workers had more overall education, more ethics education, and higher confidence and moral action scores, and were more likely to use ethics resources than nurses. Conclusion: Ethics education has a significant positive influence on moral confidence, moral action, and use of ethics resources by nurses and social workers. C1 [Grady, Christine; Danis, Marion] Ctr Clin, Dept Clin Bioeth, Natl Inst Hlth, Bethesda, MD 20892 USA. [Soeken, Karen L.] Univ Maryland, College Pk, MD 20742 USA. [Taylor, Carol] Georgetown Univ, Ctr Clin Bioeth, Washington, DC 20057 USA. [Ulrich, Connie M.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Grady, C (reprint author), Ctr Clin, Dept Clin Bioeth, Natl Inst Hlth, Bldg 10 1C118,9000 Rockville Pike, Bethesda, MD 20892 USA. EM cgrady@cc.nih.gov NR 23 TC 40 Z9 43 U1 4 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 4 BP 4 EP 11 DI 10.1080/15265160802166017 PG 8 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 318SU UT WOS:000257113900004 ER PT J AU Resnik, DB AF Resnik, David B. TI Closing Loopholes in the Federal Research Regulations: Some Practical Problems SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID PEDIATRIC RESEARCH; BENEFIT; RISK C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop NH 06,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 18 TC 0 Z9 0 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 11 BP 6 EP 8 AR PII 906418481 DI 10.1080/15265160802524660 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 380KE UT WOS:000261463800003 PM 19061095 ER PT J AU Resnik, DB AF Resnik, David B. TI Research ethics consultation at the National Institute of Environmental Health Sciences SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop NH 06,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnickd@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 2 TC 2 Z9 2 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 3 BP 40 EP 42 DI 10.1080/15265160802109512 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 317OV UT WOS:000257030400019 PM 18570102 ER PT J AU Lev, O AF Lev, Ori TI Assessing the importance of maintaining soldiers' moral responsibility - Possible trade-offs SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Lev, Ori] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Lev, Ori] NIH, Social & Behav Res Branch, Bethesda, MD 20892 USA. RP Lev, O (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM levo@mail.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 2 BP 44 EP 45 DI 10.1080/15265160802015073 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 309AV UT WOS:000256433000012 PM 18570078 ER PT J AU Resnik, DB AF Resnik, David B. TI Hidden sources of private industry funding SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID LUNG-CANCER C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop NH 06,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnick@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-01, ZIA ES102646-02] NR 8 TC 4 Z9 4 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 8 BP 60 EP 61 DI 10.1080/15265160802318105 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 350DD UT WOS:000259331900024 PM 18802869 ER PT J AU Hull, SC Sharp, RR Botkin, JR Brown, M Hughes, M Sugarman, J Schwinn, D Sankar, P Bolcic-Jankovic, D Clarridge, BR Wilfond, BS Katz, T AF Hull, Sara Chandros Sharp, Richard R. Botkin, Jeffrey R. Brown, Mark Hughes, Mark Sugarman, Jeremy Schwinn, Debra Sankar, Pamela Bolcic-Jankovic, Dragana Clarridge, Brian R. Wilfond, Benjamin S. Katz, Treuman TI Patients' Views on Identifiability of Samples and Informed Consent for Genetic Research SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE genetic research; identifiable information; informed consent; non-identifiable information; stored samples ID GENOMIC RESEARCH; TISSUE; POPULATION; ATTITUDES; EXPERIENCE; STATEMENT; DNA AB It is unclear whether the regulatory distinction between non-identifiable and identifiable informationinformation used to determine informed consent practices for the use of clinically derived samples for genetic researchis meaningful to patients. The objective of this study was to examine patients' attitudes and preferences regarding use of anonymous and identifiable clinical samples for genetic research. Telephone interviews were conducted with 1,193 patients recruited from general medicine, thoracic surgery, or medical oncology clinics at five United States academic medical centers. Wanting to know about research being done was important to 72% of patients when samples would be anonymous and to 81% of patients when samples would be identifiable. Only 17% wanted to know about the identifiable scenario but not the anonymous scenario (i.e., following the regulatory distinction). Curiosity-based reasons were the most common (37%) among patients who wanted to know about anonymous samples. Of patients wanting to know about either scenario, approximately 57% would require researchers to seek permission, whereas 43% would be satisfied with notification only. Patients were more likely to support permission (versus notification) in the anonymous scenario if they had more education, were Black, less religious, in better health, more private, and less trusting of researchers. The sample, although not representative of the general population, does represent patients at academic medical centers whose clinical samples may be used for genetic research. Few patients expressed preferences consistent with the regulatory distinction between non-identifiable and identifiable information. Data from this study should cause policy-makers to question whether this distinction is useful in relation to research with previously collected clinically derived samples. C1 [Hull, Sara Chandros] NHGRI, Dept Clin Bioeth, NIH, Bethesda, MD 20892 USA. [Sharp, Richard R.] Cleveland Clin, Cleveland, OH 44106 USA. [Botkin, Jeffrey R.] Univ Utah, Salt Lake City, UT 84112 USA. [Brown, Mark] Univ Arizona, Coll Med, Tucson, AZ 85721 USA. [Hughes, Mark; Sugarman, Jeremy] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Sankar, Pamela] Univ Penn, Philadelphia, PA 19104 USA. [Bolcic-Jankovic, Dragana; Clarridge, Brian R.] Univ Massachusetts, Survey Res Ctr, Amherst, MA 01003 USA. [Katz, Treuman] Childrens Hosp & Reg Med Ctr, Ctr Pediat Bioeth, Seattle, WA USA. RP Hull, SC (reprint author), NHGRI, Dept Clin Bioeth, NIH, 10 Ctr Dr,Suite 1C118, Bethesda, MD 20892 USA. EM shull@mail.nih.gov FU Division of Intramural Research; National Human Genome Research Institute; National Institutes of Health FX Funding for this study was provided by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The authors would like to thank David Wendler, Ezekiel Emanuel, and Colleen McBride for their critical review of drafts of this manuscript, Ellen Wright Clayton for her input on the design of the study, and Liza Dawson for her assistance with recruitment. The authors of this article are responsible for its contents. No statement in this article should be construed as an official position of the National Human Genome Research Institute, National Institutes of Health, or Department of Health and Human Services. NR 25 TC 56 Z9 56 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 10 BP 62 EP 70 AR PII 905338224 DI 10.1080/15265160802478404 PG 9 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 371MD UT WOS:000260834500023 PM 19003716 ER PT J AU Grady, C Danis, M Soeken, KL O'Donnell, P Taylor, C Farrar, A Ulrich, CM AF Grady, Christine Danis, Marion Soeken, Karen L. O'Donnell, Patricia Taylor, Carol Farrar, Adrienne Ulrich, Connie M. TI Response to peer commentary on "Does Ethics Education Influence the Moral Action of Practicing Nurses and Social Workers?" SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Grady, Christine; Danis, Marion] Ctr Clin, Dept Clin Bioeth, Natl Inst Hlth, Bethesda, MD 20892 USA. [Soeken, Karen L.] Univ Maryland, College Pk, MD 20742 USA. [Taylor, Carol] Georgetown Univ, Ctr Clin Bioeth, Washington, DC 20057 USA. [Ulrich, Connie M.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Grady, C (reprint author), Ctr Clin, Dept Clin Bioeth, Natl Inst Hlth, Bldg 10 1C118,9000 Rochville Pike, Bethesda, MD 20892 USA. EM cgrady@cc.nih.gov NR 3 TC 3 Z9 3 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 4 BP W1 EP W2 DI 10.1080/15265160802155523 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 318SU UT WOS:000257113900001 ER PT J AU Hull, SC Wilfond, BS AF Hull, Sara Chandros Wilfond, Benjamin S. TI What Does It Mean To Be Identifiable? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Letter AB . C1 [Hull, Sara Chandros] NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. [Wilfond, Benjamin S.] Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Hull, SC (reprint author), NIH, Dept Clin Bioeth, 10 Ctr Dr,Suite 1C118, Bethesda, MD 20892 USA. EM shull@mail.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 10 BP W7 EP W8 AR PII 905338889 DI 10.1080/15265160802519538 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 371MD UT WOS:000260834500032 PM 19003695 ER PT J AU Hamburg, NM Larson, MG Vita, JA Vasan, RS Keyes, MJ Widlansky, ME Fox, CS Mitchell, GF Levy, D Meigs, JB Benjamin, EJ AF Hamburg, Naomi M. Larson, Martin G. Vita, Joseph A. Vasan, Ramachandran S. Keyes, Michelle J. Widlansky, Michael E. Fox, Caroline S. Mitchell, Gary F. Levy, Daniel Meigs, James B. Benjamin, Emelia J. TI Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham Offspring participants without clinical evidence of cardiovascular disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VASCULAR ENDOTHELIAL FUNCTION; FLOW-MEDIATED DILATION; DIABETES-MELLITUS; PLASMA-GLUCOSE; DYSFUNCTION; RISK; OBESITY; ADULTS; ASSOCIATION; CHOLESTEROL AB The metabolic syndrome (MS), a clustering of metabolic disturbances, is associated with increased cardiovascular risk. Limited information is available about the relations between MS, insulin resistance, and vascular function. We measured brachial artery flow-mediated dilation (n = 2,123) and reactive hyperemia (n = 1,521) in Framingham Offspring participants without diabetes or clinical cardiovascular disease (mean age 59 +/- 9 years, 57% women). MS, determined by National Cholesterol Education Program criteria, was present in 36% of participants. Insulin resistance was determined using Homeostatic Model Assessment. In age- and gender-adjusted models, MS was associated with lower flow-mediated dilation and reactive hyperemia. There was progressively lower vasodilator function with increasing number of MS components (p for trend <0.0001). In multivariable models adjusting for the 5 MS components as continuous variables, MS (presence vs absence) remained associated with lower flow-mediated dilation (2.84 +/- 0.12% vs 3.17 +/- 0.08%, p = 0.0496) and reactive hyperemia (50.8 +/- 1.0 vs 54.4 +/- 0.7 cm/s, p = 0.009). Insulin resistance was inversely associated with flow-mediated dilation and reactive hyperemia in age- and gender-adjusted models, but these relations were not significant in models adjusting for the MS components. In conclusion, our observations are consistent with the hypothesis that MS and insulin resistance impair vascular function predominantly through the influence of the component metabolic abnormalities that comprise MS. (c) 2008 Elsevier Inc. All rights reserved. C1 [Hamburg, Naomi M.; Vita, Joseph A.; Vasan, Ramachandran S.; Widlansky, Michael E.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. [Larson, Martin G.; Vasan, Ramachandran S.; Keyes, Michelle J.; Fox, Caroline S.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.; Keyes, Michelle J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Waltham, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Div Gen Med, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. EM emelia@bu.edu OI Vita, Joseph/0000-0001-5607-1797; Hamburg, Naomi/0000-0001-5504-5589; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24 HL 04334, HL 060040, HL 70100, K24 HL004334, N01 HC 25195, N01 HC025195, N01HC25195, R01 HL060040, R01 HL060040-01A1, R01 HL060040-02, R01 HL060040-03, R01 HL060040-04, R01 HL070100, R01 HL070100-01, R01 HL070100-02, R01 HL070100-03, R01 HL070100-04, R01 HL076784, R01 HL076784-01, R01 HL076784-02, R01 HL076784-03, R01 HL076784-04] NR 30 TC 53 Z9 55 U1 0 U2 5 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2008 VL 101 IS 1 BP 82 EP 88 DI 10.1016/j.amjcard.2007.07.053 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 248FC UT WOS:000252136400015 PM 18157970 ER PT J AU Padayatty, SJ Levine, M AF Padayatty, Sebastian J. Levine, Mark TI Fruit and vegetables: think variety, go ahead, eat! SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID CORONARY-HEART-DISEASE; VITAMIN-C; CARDIOVASCULAR-DISEASE; DIETARY FIBER; ISCHEMIC-STROKE; ASCORBIC-ACID; RISK; COHORT; METAANALYSIS; MORTALITY C1 [Levine, Mark] NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIDDKD, Mol & Clin Nutr Sect, NIH, Bldg 10,Room 4D52-MSC 1372, Bethesda, MD 20892 USA. EM MarkL@intra.niddk.nih.gov RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 NR 23 TC 21 Z9 22 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2008 VL 87 IS 1 BP 5 EP 7 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 250KJ UT WOS:000252298500003 PM 18175730 ER PT J AU Sahyoun, NR Anderson, AL Tylavsky, FA Lee, JS Sellmeyer, DE Harris, TB AF Sahyoun, Nadine R. Anderson, Amy L. Tylavsky, Frances A. Lee, Jung Sun Sellmeyer, Deborah E. Harris, Tamara B. CA Hlth Aging TI Dietary diabete glycemic index and glycemic load and the risk of type 2 diabetes in older adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet; glycemic index; glycemic load; type 2 diabetes; older adults ID INSULIN-RESISTANCE ATHEROSCLEROSIS; FIBER INTAKE; CARBOHYDRATE; DISEASE; WOMEN; PREVENTION; PREVALENCE; AMERICAN; MELLITUS; TABLE AB Background: It is unclear whether immediate dietary effects on blood glucose influence the risk of developing type 2 diabetes. Objective: The objective of this study was to examine whether the dietary glycemic index (GI) and glycemic load (GL) were associated with the risk of type 2 diabetes in older adults. Design: The Health, Aging, and Body Composition Study is a prospective cohort study of 3075 adults who were 70-79 y old at baseline (n = 1898 for this analysis). The intakes of specific nutrients and food groups and the risk of type 2 diabetes over a 4-y period were examined according to dietary GI and GL. Results: Dietary GI was positively associated with dietary carbohydrate and negatively associated with the intakes of protein, total fat, saturated fat, alcohol, vegetables, and fruit. Dietary GL was positively associated with dietary carbohydrate, fruit, and fiber and negatively associated with the intakes of protein, total fat, saturated fat, and alcohol. Persons in the higher quintiles of dietary GI or GL did not have a significantly greater incidence of type 2 diabetes. Conclusions: These findings do not support a relation between dietary GI or GL and the risk of type 2 diabetes in older adults. Because dietary GI and GL show strong nutritional correlates, the overall dietary pattern should be considered. C1 [Sahyoun, Nadine R.; Anderson, Amy L.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Lee, Jung Sun] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Sellmeyer, Deborah E.] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. [Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA. RP Sahyoun, NR (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM nsahyoun@umd.edu RI Sahyoun, Nadine/G-2608-2011 FU Intramural NIH HHS [Z01 AG007390-02]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 31 TC 49 Z9 51 U1 3 U2 22 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2008 VL 87 IS 1 BP 126 EP 131 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 250KJ UT WOS:000252298500018 PM 18175745 ER PT J AU Houston, DK Nicklas, BJ Ding, JZ Harris, TB Tylavsky, FA Newman, AB Lee, JS Sahyoun, NR Visser, M Kritchevsky, SB AF Houston, Denise K. Nicklas, Barbara J. Ding, Jingzhong Harris, Tamara B. Tylavsky, Frances A. Newman, Anne B. Lee, Jung Sun Sahyoun, Nadine R. Visser, Marjolein Kritchevsky, Stephen B. CA Study, HA TI Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body composition; sarcopenia; dietary protein; aging ID TRAINING-INDUCED CHANGES; SKELETAL-MUSCLE MASS; WEIGHT-LOSS; ELDERLY-WOMEN; SARCOPENIA; MEN; CARBOHYDRATE; NUTRITION; EXERCISE; VALIDITY AB Background: Dietary surveys suggest that many older, community-dwelling adults consume insufficient dietary protein, which may contribute to the age-related loss of lean mass (LM). Objective: The objective of the study was to determine the association between dietary protein and changes in total LM and nonbone appendicular LM (aLM) in older, community-dwelling men and women. Design: Dietary protein intake was assessed by using an interviewer-administered 108-item food-frequency questionnaire in men and women aged 70-79 y who were participating in the Health, Aging, and Body Composition study (n = 2066). Changes in LM and aLM over 3 y were measured by using dual-energy X-ray absorptiometry. The association between protein intake and 3-y changes in LM and aLM was examined by using multiple linear regression analysis adjusted for potential confounders. Results: After adjustment for potential confounders, energy-adjusted protein intake was associated with 3-y changes in LM [beta (SE): 8.76 (3.00), P = 0.004] and aLM [beta (SE): 5.31 (1.64), P = 0.001]. Participants in the highest quintile of protein intake lost approximate to 40% less LM and aLM than did those in the lowest quintile of protein intake ((x) over bar +/- SE: -0.501 +/- 0.106 kg compared with -0.883 +/- 0.104 kg for LM; -0.400 +/- 0.058 kg compared with -0.661 +/- 0.057 kg for aLM; P for trend < 0.01). The associations were attenuated slightly after adjustment for change in fat mass, but the results remained significant. Conclusion: Dietary protein may be a modifiable risk factor for sarcopenia in older adults and should be studied further to determine its effects on preserving LM in this population. C1 [Houston, Denise K.; Nicklas, Barbara J.; Ding, Jingzhong; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med,Sticht Ctr Aging, Winston Salem, NC 27157 USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Tylavsky, Frances A.] Univ Tennessee, Memphis, TN USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Lee, Jung Sun] Univ Georgia, Athens, GA 30602 USA. [Sahyoun, Nadine R.] Univ Maryland, College Pk, MD 20742 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Amsterdam, Netherlands. RP Houston, DK (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med,Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dhouston@wfubmc.edu RI Newman, Anne/C-6408-2013; Sahyoun, Nadine/G-2608-2011 OI Newman, Anne/0000-0002-0106-1150; FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30-AG21332] NR 29 TC 282 Z9 293 U1 7 U2 47 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2008 VL 87 IS 1 BP 150 EP 155 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 250KJ UT WOS:000252298500022 PM 18175749 ER PT J AU Padayatty, SJ Levine, M AF Padayatty, Sebastian J. Levine, Mark TI Is there a need for vitamin C supplementation of the normal diet? Effects of in vivo ascorbate depletion on adrenal function - Reply SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID GUINEA-PIG; ALDOSTERONE STIMULATION; SODIUM DEFICIENCY; ACID DEFICIENCY C1 [Padayatty, Sebastian J.; Levine, Mark] NIH, Mol & Clin Nutr Sect, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIH, Mol & Clin Nutr Sect, Bldg 10,Room 4D52 MSC 1372, Bethesda, MD 20892 USA. EM markl@intra.niddk.nih.gov RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 NR 10 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2008 VL 87 IS 1 BP 191 EP 192 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 250KJ UT WOS:000252298500031 ER PT J AU Maki, J Robinson, K Reguly, B Alexander, J Wittock, R Aguirre, A Diamandis, EP Escott, N Skehan, A Prowse, O Thayer, RE Froberg, MK Wilson, MJ Maragh, S Jakupciak, JP Wagner, PD Srivastava, S Dakubo, GD Parr, RL AF Maki, Jennifer Robinson, Kerry Reguly, Brian Alexander, Jude Wittock, Roy Aguirre, Andrea Diamandis, Eleftherios P. Escott, Nicholas Skehan, Anthony Prowse, Owen Thayer, Robert E. Froberg, M. Kent Wilson, Michael J. Maragh, Samantha Jakupciak, John P. Wagner, Paul D. Srivastava, Sudhir Dakubo, Gabriel D. Parr, Ryan L. TI Mitochondrial genome deletion aids in the identification of false- and true-negative prostate needle core biopsy specimens SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE mtDNA deletion; prostate biopsy; false-negative biopsy result; sensitivity; specificity; field cancerization ID DNA; CANCER; APOPTOSIS; MUTATIONS; ADJACENT AB We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4mt Delta) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4mt Delta was identified through long-extension polymerase chain reaction (PCR) analysis of frozen prostate cancer samples. A quantitative PCR assay was developed to measure the levels of the 3.4mt Delta in clinical samples. For normalization, amplifications of a nuclear target and total mitochondrial DNA were included. Cycle threshold data from these targets were used to calculate a score for each biopsy sample. In a pilot study of 38 benign, 29 malignant, and 41 PTM biopsy specimens, the difference between benign and malignant core biopsy specimens was well differentiated (P <. 0001), with PTM indistinguishable from malignant samples (P =.833). Results of a larger study were identical. In comparison with histopathologic examination for benign and malignant samples, the sensitivity and specificity were 80% and 71%, respectively, and the area under a receiver operating characteristic (ROC) curve was 0.83 for the deletion. In a blinded external validation study, the sensitivity and specificity were 83% and 79%, and the area under the ROC curve was 0.87. The 3.4mt Delta may be useful in defining malignant, benign, and PTM prostate tissues. C1 [Maki, Jennifer; Robinson, Kerry; Reguly, Brian; Alexander, Jude; Wittock, Roy; Aguirre, Andrea; Thayer, Robert E.; Dakubo, Gabriel D.; Parr, Ryan L.] Genesis Genom, Thunder Bay, ON P7A 7T1, Canada. [Diamandis, Eleftherios P.] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. [Escott, Nicholas] Thunder Bay Reg Hlth Sci Ctr, Dept Pathol, Thunder Bay, ON, Canada. [Skehan, Anthony; Prowse, Owen] Thunder Bay Reg Hlth Sci Ctr, Dept Urol, Thunder Bay, ON, Canada. [Froberg, M. Kent] Univ Minnesota, Dept Pathol & Lab Med, Duluth, MN 55812 USA. [Wilson, Michael J.] VA Med Ctr Res Serv, Dept Lab Med, Minneapolis, MN USA. [Maragh, Samantha] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA. [Jakupciak, John P.] Cipher Syst, Crofton, MD USA. [Wagner, Paul D.; Srivastava, Sudhir] Natl Canc Inst, Div Canc Prevent, Rockville, MD USA. RP Parr, RL (reprint author), Genesis Genom, 1000-290 Munro St, Thunder Bay, ON P7A 7T1, Canada. OI Diamandis, Eleftherios/0000-0002-1589-820X NR 18 TC 27 Z9 27 U1 2 U2 4 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2008 VL 129 IS 1 BP 57 EP 66 DI 10.1309/UJJTH4HFEPWAQ78Q PG 10 WC Pathology SC Pathology GA 243VF UT WOS:000251824700005 PM 18089489 ER PT J AU Li, SX Li, J Epstein, DH Zhang, XY Kosten, TR Lu, L AF Li, Su-xia Li, Jing Epstein, David H. Zhang, Xiang Yang Kosten, Thomas R. Lu, Lin TI Serum cortisol secretion during heroin abstinence is elevated only nocturnally SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE circadian rhythm; cortisol; detoxification; heroin abstainers ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL RESPONSE; CIGARETTE-SMOKING; REWARD PATHWAYS; DRUG-DEPENDENCE; BETA-ENDORPHIN; STRESS; COCAINE; WITHDRAWAL; ADDICTS AB Several studies indicate abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) during acute opiate withdrawal, but protracted withdrawal has gotten less study. The current study further characterized the 24-hour time course of plasma cortisol levels in heroin-dependent individuals who were abstinent for 10-15 days, which is beyond the 5 days of acute withdrawal, compared to demographically matched healthy controls using samples collected every 3 hours over 24 hours and assessed with radioimmunoassay (RIA). The abstinent heroin-dependent participants had significantly higher plasma cortisol levels nocturnally suggesting a loss of diurnal variation in these heroin subjects. C1 [Li, Su-xia; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. [Li, Su-xia; Li, Jing] Sichuan Univ, W China Hosp, Inst Mental Hlth, Chengdu 610064, Peoples R China. [Epstein, David H.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Zhang, Xiang Yang; Kosten, Thomas R.] Baylor Coll Med, Div Alcohol & Addict Disorders, Houston, TX 77030 USA. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xue Yuan Rd, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [K05 DA000454, K05-DA0454] NR 25 TC 7 Z9 8 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2008 VL 34 IS 3 BP 321 EP 328 DI 10.1080/00952990802013664 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 291UH UT WOS:000255221800008 PM 18428074 ER PT J AU Kanneganti, P Nelson, RA Boyd, SJ Ziegelstein, RC Gorelick, DA AF Kanneganti, Praveen Nelson, Richard A. Boyd, Susan J. Ziegelstein, Roy C. Gorelick, David A. TI Exercise stress testing in recently abstinent chronic cocaine abusers SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE abstinent; cocaine; exercise stress test; echocardiography ID CARDIOVASCULAR COMPLICATIONS; INTRAVENOUS COCAINE AB We compared treadmill exercise stress testing (EST) in 28 medically screened, chronic cocaine users with the cardiovascular effects of an IV cocaine challenge (25 mg or 50 mg). All subjects had a clinically normal EST and echocardiography (except 2 subjects had septal wall hypokinesis). The EST produced significantly greater increases in heart rate and rate-pressure product than did the cocaine challenges. These findings suggest that EST may not provide additional diagnostic information in medically screened cocaine users. EST may cause more cardiac work (indicated by heart rate and blood pressure) than intravenous cocaine (at the doses in this study). C1 [Kanneganti, Praveen; Nelson, Richard A.; Boyd, Susan J.; Gorelick, David A.] NIDA, Off Sci Director, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Ziegelstein, Roy C.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. RP Gorelick, DA (reprint author), NIDA, Off Sci Director, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000241-15] NR 19 TC 0 Z9 0 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2008 VL 34 IS 4 BP 489 EP 498 DI 10.1080/00952990802082214 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 318XA UT WOS:000257124900013 PM 18584578 ER PT J AU Yu, E Miotto, K Akerele, E O'Brien, CP Ling, W Kleber, H Fischman, MW Elkashef, A Herman, BH Al-Ghananeem, AM AF Yu, Elmer Miotto, Karen Akerele, Evaristo O'Brien, Charles P. Ling, Walter Kleber, Herbert Fischman, Marian W. Elkashef, Ahmed Herman, Barbara H. Al-Ghananeem, Abeer M. TI Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE clinical trial; LC-MS/MS; lofexidine; pharmacokinetic; substance abuse ID WITHDRAWAL; CLONIDINE AB Objectives: The objective of this investigation was to characterize the pharmacokinetic profile of lofexidine. Lofexidine is an orally bioavailable alpha 2- adrenergic receptor agonist analogue of clonidine that acts centrally to suppress opiate withdrawal symptoms. Methods: During the detoxification period of a phase 3 placebo-controlled, randomized, double-blind trial, six subjects were entered in this preliminary pharmacokinetic study. Results: Pharmacokinetic analysis of plasma samples collected during study day 7 indicated that Cmax was 3242 +/- 917 ng/L. The mean trough levels between the study days were not significantly different (p > .05), suggesting that the subjects were at steady-state. Conclusions: Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine clinical pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis. C1 [Al-Ghananeem, Abeer M.] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA. [Yu, Elmer; O'Brien, Charles P.] Univ Penn, Philadelphia, PA 19104 USA. [Yu, Elmer; O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Miotto, Karen; Ling, Walter] Univ Calif Los Angeles, Los Angeles, CA USA. [Akerele, Evaristo; Kleber, Herbert; Fischman, Marian W.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, New York, NY 10032 USA. [Miotto, Karen; Ling, Walter] Long Beach Vet Affairs Med Ctr, Los Angeles, CA USA. [Elkashef, Ahmed; Herman, Barbara H.] NIDA, Div Pharmacotherapeut & Med Consequences Drug Abu, PMC, NIH, Bethesda, MD 20892 USA. RP Al-Ghananeem, AM (reprint author), Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA. EM amalg0@email.uky.edu FU NIDA NIH HHS [Y1-DA1001] NR 7 TC 4 Z9 4 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2008 VL 34 IS 5 BP 611 EP 616 DI 10.1080/00952990802308122 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 353XV UT WOS:000259603400011 PM 18821454 ER PT J AU Kanneganti, P Huestis, MA Kolbrich, EA Goodwin, R Ziegelstein, RC Gorelick, DA AF Kanneganti, Praveen Huestis, Marilyn A. Kolbrich, Erin A. Goodwin, Robert Ziegelstein, Roy C. Gorelick, David A. TI Signal-Averaged Electrocardiogram in Physically Healthy, Chronic 3,4-Methylenedioxymethamphetamine (MDMA) Users SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Cannabis; MDMA; signal-averaged ECG; ventricular late potentials ID VENTRICULAR LATE POTENTIALS; QUANTITATIVE-ANALYSIS; ECSTASY; MARIJUANA; SMOKING; MISUSE; EVE; ECG AB Objectives: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use has been associated with cardiac arrhythmias. Markers of ventricular late potentials (VLP), which may be a precursor to malignant ventricular arrhythmias, can be detected by signal-averaged electrocardiography (SA-ECG), but not by standard ECG. Methods: We evaluated SA-ECG parameters in 21 physically healthy, recently abstinent MDMA users who also used cannabis (11 males, mean [SD] age 23.3 [4.6] years, 2.8 [2.0] years of use), 18 physically healthy cannabis users (8 males, mean [SD] age 26.6 [7.1] years, 11.2 [5.4] years of use) and 54 non-drug-using controls (21 males, mean [SD] age 28.4 [7.8] years). We analyzed three SA-ECG parameters considered markers of VLPs: duration of filtered QRS complex (fQRS), duration of low amplitude potentials during terminal 40 ms of QRS complex (LAS40), and root mean square voltage during terminal 40 ms of QRS complex (RMS40). Results: MDMA users, cannabis users, and non-drug-using controls did not differ significantly from each other in fQRS, LAS40, or RMS40 values or in the proportion of subjects with abnormal SA-ECG parameters. There were significant gender differences among controls, but not among MDMA users. Conclusion: These findings suggest that chronic MDMA use is neither quantitatively nor qualitatively associated with a high prevalence of abnormal SA-ECG parameters indicative of VLP markers. C1 [Kanneganti, Praveen; Huestis, Marilyn A.; Kolbrich, Erin A.; Goodwin, Robert; Gorelick, David A.] NIDA, Intramural Res Program, US Dept HHS, NIH, Baltimore, MD 21224 USA. [Ziegelstein, Roy C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. RP Gorelick, DA (reprint author), NIDA, Intramural Res Program, US Dept HHS, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000240-15, Z01 DA000241-15, Z01 DA000468-04] NR 26 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 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2008 VL 34 IS 6 BP 712 EP 720 AR PII 904099373 DI 10.1080/00952990802308254 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 374BV UT WOS:000261018200006 PM 18855243 ER PT J AU De Lucca, AJ Klich, M Boue, S Cleveland, TE Sien, T Walsh, TJ AF De Lucca, Anthony J. Klich, Maren Boue, Stephen Cleveland, Thomas E. Sien, Tien Walsh, Thomas J. TI Fungicidal activity of plant saponin CAY-1 for fungi isolated from diseased Vitis fruit and stems SO AMERICAN JOURNAL OF ENOLOGY AND VITICULTURE LA English DT Article DE CAY-1; saponin; grapes; fungi; fungicidal; Aspergillus; Penicillium ID CANDIDA-ALBICANS; GRAPES; ASPERGILLUS; OCHRATOXIN; EMPHASIS; GROWTH AB Members of 10 fungal genera were isolated from diseased grape berries and stems collected in a local vineyard. These fungi were identified as Alternaria sp., Aspergillus japonicus, Cladosporium cladosporioides, Collelotrichum sp., Curvularia brachyspora, Epicoccum purpurascens, Greeneria uvicola, Nigrospora sphaerica, Trichoderma sp., Penicillium sclerotiorum and P. thomii. CAY-1, a fungicidal saponin in cayenne pepper (Capsicum frutescens) was significantly (p <= 0.05) lethal to the germinating (incubated 8 hr) but not the nongerminated (0 hr incubation) conidia of all the fungi except Alternaria and E. purpurascens at concentrations greater than 7.5 mu M. CAY-1 was ineffective against the conidia of all the isolated fungi incubated 24 hr prior to mixing with the saponin. Results show that, in vitro, CAY-1 is lethal to these fungi only during their early germination cycle. C1 [De Lucca, Anthony J.; Klich, Maren; Boue, Stephen; Cleveland, Thomas E.] USDA ARS, So Reg Res Ctr, New Orleans, LA 70124 USA. [Sien, Tien; Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA. RP De Lucca, AJ (reprint author), USDA ARS, So Reg Res Ctr, 1100 Robert E Lee Blvd, New Orleans, LA 70124 USA. EM adelucca@srrc.ars.usda.gov NR 34 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC ENOLOGY VITICULTURE PI DAVIS PA PO BOX 1855, DAVIS, CA 95617-1855 USA SN 0002-9254 J9 AM J ENOL VITICULT JI Am. J. Enol. Vitic. PY 2008 VL 59 IS 1 BP 67 EP 72 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology; Horticulture SC Biotechnology & Applied Microbiology; Food Science & Technology; Agriculture GA 273KC UT WOS:000253927900009 ER PT J AU Jukic, AMZ Weinberg, CR Wilcox, AJ McConnaughey, DR Hornsby, P Baird, DD AF Jukic, Anne Marie Zaura Weinberg, Clarice R. Wilcox, Allen J. McConnaughey, D. Robert Hornsby, Paige Baird, Donna D. TI Accuracy of reporting of menstrual cycle length SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE interviews; menstrual cycle; questionnaires; reproducibility of results; research design ID BREAST-CANCER; EXPOSURE; WOMEN; WATER; RISK AB There are many studies based on self-reported menstrual cycle length, yet little is known about the validity of this measure. The authors used data collected in 1990 from 352 women born in Chicago, Illinois, aged 37-39 years. Women reported their usual cycle length and behavioral and reproductive characteristics at study enrollment and then completed daily menstrual diaries for up to 6 months. The authors compared this observed cycle length (geometric mean) with the reported length by using kappa coefficients. To assess systematic effects, they performed linear regression of the difference between reported and observed cycle length. Agreement between observed and reported cycle length was moderate. The crude overall kappa coefficient was 0.33; the kappa adjusted for within-woman sampling variability was 0.45 (95% confidence interval: 0.36, 0.55). On average, women overestimated their cycle length by 0.7 days (95% confidence interval: 0.3, 1.0). Reporting by sexually active women and women with a history of infertility was more accurate. Parity, body mass index, prior medical evaluation for irregular cycles, and exercise were all associated with systematic reporting differences. Studies that rely on self-reported cycle length could be prone to artifactual findings because of systematic covariate effects on reporting. C1 [Jukic, Anne Marie Zaura; Wilcox, Allen J.; Hornsby, Paige; Baird, Donna D.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Weinberg, Clarice R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Jukic, AMZ (reprint author), NIEHS, Epidemiol Branch, POb 12233, Res Triangle Pk, NC 27709 USA. EM jukica@niehs.nih.gov RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 19 TC 37 Z9 39 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2008 VL 167 IS 1 BP 25 EP 33 DI 10.1093/aje/kwm265 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244KF UT WOS:000251864100006 PM 17928401 ER PT J AU Wong, TY Cheung, N Islam, FMA Klein, R Criqui, MH Cotch, MF Carr, JJ Klein, BEK Sharrett, AR AF Wong, Tien Y. Cheung, Ning Islam, F. M. Amirul Klein, Ronald Criqui, Michael H. Cotch, Mary Frances Carr, J. Jeffrey Klein, Barbara E. K. Sharrett, A. Richey TI Relation of retinopathy to coronary artery calcification - The multi-ethnic study of atherosclerosis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE arterioles; atherosclerosis; cardiovascular diseases; coronary disease; diabetic retinopathy; microcirculation; retinal vessels; venules ID BEAM COMPUTED-TOMOGRAPHY; RETINAL MICROVASCULAR ABNORMALITIES; BEAVER DAM EYE; HEART-DISEASE; ASYMPTOMATIC INDIVIDUALS; DIABETIC-RETINOPATHY; SUBCLINICAL ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; VESSEL DIAMETERS; VASCULAR CALIBER AB Microvascular disease, reflected by retinal vascular changes, has been shown to predict clinical coronary heart disease. Whether retinal vascular changes are associated with subclinical coronary artery disease is unclear and was examined in this study. The authors conducted a multiethnic, population-based study of 6,147 persons aged 45-84 years, sampled from six US communities in 2002-2004, who were free of clinical cardiovascular disease. Coronary artery calcification (CAC), a noninvasive measure of subclinical coronary artery disease, was assessed by cardiac computed tomography scanning and categorized into three groups of increasing severity: none (average CAC score = 0), mild (1-100), and moderate-to-severe (> 100). Retinopathy signs and retinal vascular caliber were graded from retinal photographs following standardized protocols. After adjustment for age, gender, race/ethnicity, blood pressure, diabetes, lipid profile, smoking, and other risk factors, retinopathy was associated with having a moderate-to-severe CAC score (odds ratio = 1.43, 95% confidence interval: 1.18, 1.75). This association remained significant in both men and women and in persons with and without diabetes or hypertension. Variations in retinal vascular caliber were not significantly associated with CAC score. This study shows that retinopathy signs are independently associated with CAC, supporting the concept that common pathophysiologic processes may underlie both micro- and macrovascular disease. C1 [Wong, Tien Y.; Cheung, Ning; Islam, F. M. Amirul] Univ Melbourne, Ctr Eye Res Australia, Sch Med, Dept Ophthalmol, Melbourne, Vic 3002, Australia. [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117548, Singapore. [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Criqui, Michael H.] Univ Calif San Diego, Sch Med, Dept Med, San Diego, CA 92103 USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. [Carr, J. Jeffrey] Wake Forest Univ, Sch Med, Div Radiol Sci, Winston Salem, NC 27109 USA. [Sharrett, A. Richey] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, Sch Med, Dept Ophthalmol, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM twong@unimelb.edu.au RI Cheung, Ning Danny/F-2043-2013; Carr, John/A-1938-2012; OI Carr, John/0000-0002-4398-8237; Cotch, Mary Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237 FU Intramural NIH HHS [Z01 EY000403-07, NIH0010050027, Z01 EY000403-06, Z99 EY999999, ZIA EY000403-08, ZIA EY000403-09, ZIA EY000403-10, ZIA EY000403-11, ZIA EY000403-12, ZIA EY000403-13, ZIA EY000403-14, ZIA EY000403-15]; NHLBI NIH HHS [HL69979-03, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169] NR 45 TC 35 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2008 VL 167 IS 1 BP 51 EP 58 DI 10.1093/aje/kwm256 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244KF UT WOS:000251864100009 PM 17893402 ER PT J AU Chen, H O'Reilly, EJ Schwarzschild, MA Ascherio, A AF Chen, Honglei O'Reilly, Eilis J. Schwarzschild, Michael A. Ascherio, Alberto TI Peripheral inflammatory biomarkers and risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE biological markers; C-reactive protein; inflammation; interleukin-6; odds ratio; Parkinson disease; tumor necrosis factor-alpha ID C-REACTIVE PROTEIN; URIC-ACID LEVELS; SUBSTANTIA-NIGRA; TNF-ALPHA; MEN; PLASMA; WOMEN; MICE; IL-6; MICROGLIA AB Experimental and postmortem evidence indicates a role of neuroinflammation in the pathogenesis of Parkinson's disease. The authors prospectively examined whether plasma concentrations of inflammatory biomarkers assessed before Parkinson's disease diagnosis were predictive of future risk of the disease in a nested case-control study in the United States (1993-2002), including 84 incident cases and 165 matched controls. Blood was collected from patients on average 4.3 years before the diagnosis. After adjustment for potential confounders, higher level of interleukin-6 was associated with a greater risk of Parkinson's disease. Compared with the lowest quintile, the odds ratios were 1.5 for the second, 1.6 for the third, 2.7 for the fourth, and 3.4 for the fifth quintiles (p for trend = 0.03). In contrast, concentrations of other inflammatory biomarkers including C-reactive protein, fibrinogen, and tumor necrosis factor-alpha receptors were not related to the risk. These data suggest that men with high plasma concentrations of interleukin-6 have an increased risk of developing Parkinson's disease. However, this finding should be interpreted with caution because of the small sample size and the lack of associations with other biomarkers of inflammation. C1 [O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM aascheri@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS048517] NR 29 TC 119 Z9 126 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2008 VL 167 IS 1 BP 90 EP 95 DI 10.1093/aje/kwm260 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244KF UT WOS:000251864100014 PM 17890755 ER PT J AU Taylor, JG Ackah, D Cobb, C Orr, N Percy, MJ Sachdev, V Machado, R Castro, O Kato, GJ Chanock, SJ Gladwin, MT AF Taylor, James G. Ackah, Diana Cobb, Crystal Orr, Nick Percy, Melanie J. Sachdev, Vandana Machado, Roberto Castro, Oswaldo Kato, Gregory J. Chanock, Stephen J. Gladwin, Mark T. TI Mutations and polymorphisms in hemoglobin genes and the risk of pulmonary hypertension and death in sickle cell disease SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ALPHA-THALASSEMIA; SC DISEASE; HAPLOTYPE RECONSTRUCTION; CLUSTER HAPLOTYPES; LEG ULCERS; ANEMIA; HYDROXYUREA; HEMOLYSIS; AFRICA; PATHOGENESIS AB Pulmonary hypertension is a common complication of sickle cell disease (SCD) and a risk factor for early death. Hemolysis may participate in its pathogenesis by limiting nitric oxide (NO) bioavailability and producing vasculopathy. We hypothesized that hemoglobin mutations that diminish hemolysis in SCD would influence pulmonary hypertension susceptibility. Surprisingly, coincident alpha-thalassemia (Odds Ratio [OR] = 0.95, 95% Cl = 0.46-1.94, P = NS) was not associated with pulmonary hypertension susceptibility in homozygous SCD. However, pulmonary hypertension cases were less likely to have hemoglobin SC (OR = 0.18, 95% confidence interval [Cl] = 0.06-0.51, P = 0.0005) or S beta(+) thalassemia (OR = 0.25,95% Cl = 0.06-1.16, P = 0.10). These compound heterozygotes may be protected from pulmonary hypertension because of reduced levels of intravascular hemolysis, but develop this complication at a lower rate possibly due to the presence of non-hemolytic risk factors such as renal dysfunction, iron overload and advancing age. Despite this protective association, patients with SC who did develop pulmonary hypertension remained at significant risk for death during 49 months of follow-up (Hazard Ratio = 8.20, P = 0.0057). C1 [Taylor, James G.; Ackah, Diana; Cobb, Crystal; Machado, Roberto; Kato, Gregory J.; Gladwin, Mark T.] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Orr, Nick; Chanock, Stephen J.] NCI, Sect Genet Variat, NIH, Gaithersburg, MD USA. [Percy, Melanie J.] Belfast City Hosp, Dept Haematol, Belfast BT9 7AD, Antrim, North Ireland. [Sachdev, Vandana] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. [Castro, Oswaldo] Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Castro, Oswaldo] Howard Univ, Coll Med, Dept Med, Washington, DC 20059 USA. [Kato, Gregory J.; Gladwin, Mark T.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Chanock, Stephen J.] NCI, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. RP Taylor, JG (reprint author), NHLBI, Vasc Med Branch, NIH, Bldg 10-CRC,Room 5-5140,10 Ctr Dr MSC-1476, Bethesda, MD 20892 USA. EM jamesta@mail.nih.gov RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS [ZIA HL006012-01, Z99 HL999999] NR 55 TC 35 Z9 35 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2008 VL 83 IS 1 BP 6 EP 14 DI 10.1002/ajh.21035 PG 9 WC Hematology SC Hematology GA 249VV UT WOS:000252259200003 PM 17724704 ER PT J AU Gordeuk, VR Sachdev, V Taylor, JG Gladwin, MT Kato, G Castro, SL AF Gordeuk, Victor R. Sachdev, Vandana Taylor, James G. Gladwin, Mark T. Kato, Gregory Castro, Swaldo L. TI Relative systemic hypertension in associated with risk of pulmonary patients with sickle cell disease is hypertension and renal insufficiency SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID NITRIC-OXIDE BIOAVAILABILITY; BLOOD-PRESSURE; VASCULAR INSTABILITY; DEATH; HEMOLYSIS; HEMOGLOBIN; RESISTANCE; ANEMIA; ADULTS; MOUSE AB We analyzed entry data from 163 adult hemoglobin SS and S beta(0) thalassemia patients enrolled in the prospective Sickle Cell Pulmonary Hypertension Screening Study and stratified their ECHO-determined tricuspid regurgitant jet velocity (TRV) and serum creatinine concentration according to three systemic blood pressure categories. TRV was >= 2.5 m/sec in 27% of the patients with systolic blood pressure (SBP) < 120 mmHg and diastolic blood pressure (DBP) < 70 mmHg, in 37% with SBP 120-139 mmHg or DBP 70-89 mmHg, and in 93% with SBP 140 mmHg or DBP 90 mmHg or higher (P < 0.0005 for trend). Serum creatinine concentration was 1.0 mg/dL or higher in 7% of patients with SBP < 120 mmHg and DBP < 70 mmHg, in 17% with SBP 120-139 mmHg or DBP 70-89 mmHg and 50% with SEP 140 mmHg or DBP 90 mmHg or higher (P < 0.0005 for trend). Over 2 years of follow-up, there were trends for more frequent progression to elevated TRV (P = 0.073) or creatinine (P = 0.037) values according to the higher systemic blood pressure categories. Our findings suggest that systemic SBP 120-139 mmHg or DBP 70-89 mmHg defines a category of relative systemic hypertension in patients with sickle cell disease that is associated with increased risk for pulmonary hypertension and renal dysfunction. Whether antihypertensive and/or nitric oxide donor therapy in sickle cell disease patients with relative hypertension prevents these and other complications should be determined by clinical trials. C1 [Gordeuk, Victor R.; Castro, Swaldo L.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20060 USA. [Gordeuk, Victor R.; Castro, Swaldo L.] Howard Univ, Dept Med, Washington, DC 20059 USA. [Sachdev, Vandana; Taylor, James G.; Gladwin, Mark T.; Kato, Gregory] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. RP Gordeuk, VR (reprint author), Howard Univ, Ctr Sickle Cell Dis, 2041 Georgia Ave NW, Washington, DC 20060 USA. EM vgordeuk@howard.edu RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS [ZIA HL006012-01, ZIA HL006012-02]; NCRR NIH HHS [2M01 RR10284-10, M01 RR010284]; NHLBI NIH HHS [1 R01 HL079912-02, 2 R25 HL003679-08, R01 HL079912, R25 HL003679] NR 28 TC 48 Z9 53 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2008 VL 83 IS 1 BP 15 EP 18 DI 10.1002/ajh.21016 PG 4 WC Hematology SC Hematology GA 249VV UT WOS:000252259200004 PM 17696198 ER PT J AU Aliyu, ZY Kato, GJ Taylor, J Babadoko, A Mamman, AI Gordeuk, VR Gladwin, MT AF Aliyu, Zakari Y. Kato, Gregory J. Taylor, James Babadoko, Aliyu Mamman, Aisha I. Gordeuk, Victor R. Gladwin, Mark T. TI Sickle cell disease and pulmonary hypertension in Africa: A global perspective and review of epidemiology, pathophysiology, and management SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID ACUTE CHEST SYNDROME; NITRIC-OXIDE BIOAVAILABILITY; ISCHEMIC OPTIC NEUROPATHY; NATRIURETIC PEPTIDE; RISK-FACTORS; HEPATITIS-C; HEMOLYSIS; DEATH; THERAPY; HEMOGLOBIN AB Secondary pulmonary hypertension (PAH) has been shown to have a prevalence of 30% in patients with sickle cell disease (SCD) with mortality rates of 40% at 40 months after diagnosis in the United States. The burden of SCD is highest in sub-Saharan Africa, especially in Nigeria (West Africa), where approximately 6 million people are afflicted. The true global incidence, prevalence, and burden of SCD and its associated end organ complications however remain unknown. Chronic hemolysis represents a prominent mechanistic pathway in the pathogenesis of SCD-associated pulmonary hypertension via a nitric oxide (NO) scavenging and abrogation of NO salutatory effects on vascular function, including smooth muscle relaxation, downregulation of endothelial adhesion molecules and inhibition of platelet activation. Many known infectious risk factors for PAH are also hyperendemic in Africa, including Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS), chronic hepatitis B and C, and possibly malaria. Interactions between these infectious complications and SCD-related hemolysis could yield an even higher prevalence of pulmonary hypertension and compound the existing global health systems challenges in managing SCD. Indeed, our preliminary analysis of African immigrants currently in the United States suggests that pulmonary hypertension represents a significant complication of SCD in the African subcontinent. There is clearly a need to include Africa and other parts of the world with high SCD prevalence in future comprehensive studies on the epidemiology and treatment of end organ complications of an aging SCD population world-wide. C1 [Aliyu, Zakari Y.; Kato, Gregory J.; Taylor, James; Gladwin, Mark T.] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Aliyu, Zakari Y.; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Aliyu, Zakari Y.; Gordeuk, Victor R.] Howard Univ, Dept Med, Washington, DC 20059 USA. [Aliyu, Zakari Y.; Babadoko, Aliyu; Mamman, Aisha I.] Ahmadu Bello Univ, Dept Hematol & Blood Transfus, Zaria, Nigeria. [Kato, Gregory J.; Gladwin, Mark T.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Aliyu, ZY (reprint author), NHLBI, Vasc Med Branch, NIH, Bldg 10-CRC,Room 5-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM aliyuz@mail.nih.gov RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS [ZIA HL005075-05, ZIA HL005075-04]; NCRR NIH HHS [2M01 RR10284-10]; NHLBI NIH HHS [2 R25 HL003679-08] NR 74 TC 33 Z9 36 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2008 VL 83 IS 1 BP 63 EP 70 DI 10.1002/ajh.21057 PG 8 WC Hematology SC Hematology GA 249VV UT WOS:000252259200013 PM 17910044 ER PT J AU Taylor, JG Woods, GM Machado, R Kato, GJ Gladwin, MT AF Taylor, James G. Woods, Gerald M. Machado, Roberto Kato, Gregory J. Gladwin, Mark T. TI Severe pulmonary hypertension in an adolescent with sickle cell disease SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article C1 [Taylor, James G.; Machado, Roberto; Kato, Gregory J.; Gladwin, Mark T.] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Woods, Gerald M.] Childrens Mercy Hosp, Div Hematol Oncol, Kansas City, MO 64108 USA. RP Taylor, JG (reprint author), NHLBI, Vasc Med Branch, NIH, Bldg 10-CRC,Room 5-5140,10 Ctr Dr MSC-1476, Bethesda, MD 20892 USA. EM jamesta@mail.nih.gov RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS [Z99 HL999999, ZIA HL006012-01, ZIA HL006014-02] NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2008 VL 83 IS 1 BP 71 EP 72 DI 10.1002/ajh.21039 PG 2 WC Hematology SC Hematology GA 249VV UT WOS:000252259200014 PM 17726682 ER PT J AU Spady, TC Ostrander, EA AF Spady, Tyrone C. Ostrander, Elaine A. TI Canine behavioral genetics: Pointing out the phenotypes and herding up the genes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Review ID DOMESTIC DOG; LINKAGE DISEQUILIBRIUM; AGGRESSIVE-BEHAVIOR; BREED DIFFERENCES; CLUSTER-ANALYSIS; NOVELTY SEEKING; GUIDE DOGS; PET DOGS; GENOME; TRAITS AB An astonishing amount of behavioral variation is captured within the more than 350 breeds of dog recognized worldwide. Inherent in observations of dog behavior is the notion that much of what is observed is breed specific and will persist, even in the absence of training or motivation. Thus, herding, pointing, tracking, hunting, and so forth are likely to be controlled, at least in part at the genetic level. Recent studies in canine genetics suggest teat small numbers of genes control major morphologic phenotypes. By extension, we hypothesize that at least some canine behaviors will also be controlled by small numbers of genes that can be readily mapped. In this review, we describe our current understanding of a representative subset of canine behaviors, as well as approaches for phenotyping, genome-wide scans, and data analysis. Finally, we discuss the applicability of studies of canine behavior to human genetics. C1 [Spady, Tyrone C.; Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 79 TC 42 Z9 44 U1 7 U2 49 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2008 VL 82 IS 1 BP 10 EP 18 DI 10.1016/j.ajhg.2007.12.001 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 263NM UT WOS:000253223800002 PM 18179880 ER PT J AU Nalls, MA Wilson, JG Patterson, NJ Tandon, A Zmuda, JM Huntsman, S Garcia, M Hu, DL Li, RL Beamer, BA Patel, KV Akylbekova, EL Files, JC Hardy, CL Buxbaum, SG Taylor, HA Reich, D Harris, TB Ziv, E AF Nalls, Michael A. Wilson, James G. Patterson, Nick J. Tandon, Arti Zmuda, Joseph M. Huntsman, Scott Garcia, Melissa Hu, Donglei Li, Rongling Beamer, Brock A. Patel, Kushang V. Akylbekova, Ermeg L. Files, Joe C. Hardy, Cheryl L. Buxbaum, Sarah G. Taylor, Herman A. Reich, David Harris, Tamara B. Ziv, Elad TI Admixture mapping of white cell count: Genetic locus responsible for lower white blood cell count in the health ABC and Jackson Heart Studies SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MULTIPLE-SCLEROSIS SUSCEPTIBILITY; MULTILOCUS GENOTYPE DATA; ADMIXED POPULATIONS; LINKAGE DISEQUILIBRIUM; CHEMOKINE RECEPTOR; ETHNIC-DIFFERENCES; DISEASE GENES; RISK; AFRICAN; ASSOCIATION AB White blood cell count (WBC) is an important clinical marker that varies among different ethnic groups. African Americans are known to have a lower WBC than European Americans. We surveyed the entire genome for loci underlying this difference in WBC by using admixture mapping. We analyzed data from African American participants in the Health, Aging, and Body Composition Study and the Jackson Heart Study. Participants of both studies were genotyped across >= 1322 single nucleotide polymorphisms that were preselected to be informative for African versus European ancestry and span the entire genome. We used these markers to estimate genetic ancestry in each chromosomal region and then tested the association between WBC and genetic ancestry at each locus. We found a locus on chromosome 1q strongly associated with WBC (P < 10(-12)). The strongest association was with a marker known to affect the expression of the Duffy blood group antigen. Participants who had both copies of the common West African allele had a mean WBC of 4.9 (SD 1.3); participants who had both common European alleles had a mean WBC of 7.1 (SD 1.3). This variant explained similar to 20% of population variation in WBC. We used admixture mapping, a novel method for conducting genetic-association studies, to find a region that was significantly associated with WBC on chromosome 1q. Additional studies are needed to determine the biological mechanism for this effect and its clinical implications. C1 [Nalls, Michael A.; Garcia, Melissa; Patel, Kushang V.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Wilson, James G.] Vet Adm Med Ctr, Jackson, MS 39216 USA. [Patterson, Nick J.; Tandon, Arti; Reich, David] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA. [Zmuda, Joseph M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Huntsman, Scott; Hu, Donglei; Ziv, Elad] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Inst Human Genet, San Francisco, CA 94143 USA. [Li, Rongling] Univ Tennessee, Dept Prevent Med, Div Biostat & Epidemiol, Memphis, TN 38163 USA. [Beamer, Brock A.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21287 USA. [Akylbekova, Ermeg L.; Buxbaum, Sarah G.] Jackson State Univ, Jackson Heart Study Coordinating Ctr, Jackson, MS 39213 USA. [Wilson, James G.; Files, Joe C.; Hardy, Cheryl L.; Taylor, Herman A.] Univ Mississippi, Med Ctr, Dept Med, Div Hematol, Jackson, MS 39216 USA. [Taylor, Herman A.] Jackson State Univ, Tougaloo Coll, Jackson, MS 39216 USA. [Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Harris, TB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. EM harris99@nia.nih.gov RI Ziv, Elad/L-5396-2014; Buxbaum, Sarah/E-1970-2013 OI Buxbaum, Sarah/0000-0002-4886-3564 FU NHLBI NIH HHS [R01 HL084107, N01-HC-95170, N01-HC-95171, N01-HC-95172, N01HC95170, N01HC95171, N01HC95172, R01 HL084107-02]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 37 TC 88 Z9 90 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2008 VL 82 IS 1 BP 81 EP 87 DI 10.1016/j.ajhg.2007.09.003 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 263NM UT WOS:000253223800009 PM 18179887 ER PT J AU Collin, RWJ Kalay, E Tariq, M Peters, T van der Zwaag, B Venselaar, H Oostrik, J Lee, K Ahmed, ZM Caylan, R Li, Y Spierenburg, HA Eyupoglu, E Heister, A Riazuddin, S Bahat, E Ansar, M Arslan, S Wollnik, B Brunner, HG Cremers, CWRJ Karaguzel, A Ahmad, W Cremers, FPM Vriend, G Friedman, TB Riazuddin, S Leal, SM Kremer, H AF Collin, Rob W. J. Kalay, Ersan Tariq, Muhammad Peters, Theo van der Zwaag, Bert Venselaar, Hanka Oostrik, Jaap Lee, Kwanghyuk Ahmed, Zubair M. Caylan, Refik Li, Yun Spierenburg, Henk A. Eyupoglu, Erol Heister, Angelien Riazuddin, Saima Bahat, Elif Ansar, Muhammad Arslan, Selcuk Wollnik, Bernd Brunner, Han G. Cremers, Cor W. R. J. Karaguzel, Ahmet Ahmad, Wasim Cremers, Frans P. M. Vriend, Gert Friedman, Thomas B. Riazuddin, Sheikh Leal, Suzanne M. Kremer, Hannie TI Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment DFNB35 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID THYROID-HORMONE RECEPTORS; DNA-BINDING DOMAIN; INNER-EAR; NUCLEAR RECEPTOR; GENE-EXPRESSION; MOUSE EMBRYOS; ERR-ALPHA; ACTIVATION; CELLS; MATURATION AB In a large consanguineous family of Turkish origin, genome-wide homozygosity mapping revealed a locus for recessive nonsyndromic hearing impairment on chromosome 14q24.3-q34.12. Fine mapping with microsatellite markers defined the critical linkage interval to a 18.7 cM region flanked by markers D14S53 and D14S1015. This region partially overlapped with the DFNB35 locus. Mutation analysis of ESRRB, a candidate gene in the overlapping region, revealed a homozygous 7 bp duplication in exon 8 in all affected individuals. This duplication results in a frame shift and premature stop codon. Sequence analysis of the ESRRB gene in the affected individuals of the original DFNB35 family and in three other DFNB35-linked consanguineous families from Pakistan revealed four missense mutations. ESRRB encodes the estrogen-related receptor beta protein, and one of the substitutions (p.A110V) is located in the DNA-binding domain of ESRRB, whereas the other three are substitutions (p.L320P, p.V342L, and p.L347P) located within the ligand-binding domain. Molecular modeling of this nuclear receptor showed that the missense mutations are likely to affect the structure and stability of these domains. RNA in situ hybridization in mice revealed that Esrrb is expressed during inner-ear development, whereas immunohistochemical analysis showed that ESRRB is present postnatally in the cochlea. Our data indicate that ESRRB is essential for inner-ear development and function. To our knowledge, this is the first report of pathogenic mutations of an estrogen-related receptor gene. C1 [Collin, Rob W. J.; Kalay, Ersan; Peters, Theo; Oostrik, Jaap; Heister, Angelien; Brunner, Han G.; Cremers, Cor W. R. J.; Cremers, Frans P. M.; Kremer, Hannie] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6525 GA Nijmegen, Netherlands. [Kalay, Ersan; Karaguzel, Ahmet] Karadeniz Tech Univ, Fac Med, Dept Med Biol, TR-61080 Trabzon, Turkey. [Tariq, Muhammad; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [van der Zwaag, Bert; Spierenburg, Henk A.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Pharmacol & Anat, NL-3584 CG Utrecht, Netherlands. [Venselaar, Hanka; Vriend, Gert] Radboud Univ Nijmegen, Ctr Mol & Biomol Informat, NL-6525 GA Nijmegen, Netherlands. [Venselaar, Hanka; Cremers, Frans P. M.; Vriend, Gert; Kremer, Hannie] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6525 GA Nijmegen, Netherlands. [Lee, Kwanghyuk; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Ahmed, Zubair M.; Riazuddin, Saima; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA. [Caylan, Refik; Arslan, Selcuk] Karadeniz Tech Univ, Fac Med, Dept Otorhinolaryngol, TR-61080 Trabzon, Turkey. [Li, Yun; Wollnik, Bernd] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany. [Li, Yun; Wollnik, Bernd] Univ Cologne, Inst Human Genet, D-50674 Cologne, Germany. [Eyupoglu, Erol] Ordu Govt Hosp, Dept Ophthalmol, TR-52200 Ordu, Turkey. [Bahat, Elif] Karadeniz Tech Univ, Fac Med, Dept Pediat Nephrol, TR-61080 Trabzon, Turkey. [Ansar, Muhammad; Ahmad, Wasim] Quaid I Azam Univ, Fac Biol Sci, Dept Biochem, Islamabad 44520, Pakistan. [Wollnik, Bernd] Istanbul Univ, Istanbul Fac Med, Dept Med Genet, TR-34390 Istanbul, Turkey. RP Kremer, H (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6525 GA Nijmegen, Netherlands. EM h.kremer@antrg.umcn.nl RI Vriend, Gert/D-6730-2011; Ansar, Muhammad/H-5967-2011; Venselaar, Hanka/D-2009-2016; Kremer, Hannie/F-5126-2010; Brunner, Han/C-9928-2013; Collin, Rob/N-3575-2014; Ansar, Muhammad/F-4808-2015; Vriend, G./H-8112-2014; Cremers, Frans/A-5625-2014; Cremers, C.W.R.J./L-4254-2015; Peters, T.A./L-4571-2015; Ahmad, Wasim/E-9713-2015; Oostrik, Jaap/A-1703-2016 OI Lee, Kwanghyuk/0000-0001-7781-9696; Ansar, Muhammad/0000-0001-5891-7063; Kremer, Hannie/0000-0002-0841-8693; FU Intramural NIH HHS; NHGRI NIH HHS [N01HG65403]; NIDCD NIH HHS [1 Z01 DC000035-10, DC03594, R01 DC003594, R29 DC003594, T32 DC000035] NR 55 TC 39 Z9 41 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2008 VL 82 IS 1 BP 125 EP 138 DI 10.1016/j.ajhg.2007.09.008 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 263NM UT WOS:000253223800013 PM 18179891 ER PT J AU Hejtmancik, JF Jiao, X Li, A Sergeev, YV Ding, X Sharma, AK Chan, CC Medina, I Edwards, AO AF Hejtmancik, J. Fielding Jiao, Xiaodong Li, Anren Sergeev, Yuri V. Ding, Xiaoyan Sharma, Anil K. Chan, Chi-Chao Medina, Igor Edwards, Albert O. TI Mutations in KCNJ13 cause autosomal-dominant snowflake vitreoretinal degeneration SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; RECTIFIER K+ CHANNEL; POTASSIUM CHANNELS; STICKLER-SYNDROME; WAGNER-SYNDROME; EXPRESSION; KIR7.1; FAMILY AB Snowflake vitreoretinal degeneration (SVD, MIM 193230) is a developmental and progressive hereditary eye disorder that affects multiple tissues within the eye. Diagnostic features of SVD include fibrillar degeneration of the vitreous humor, early-onset cataract, minute crystalline deposits in the neurosensory retina, and retinal detachment. A genome-wide scan previously localized the genetic locus for SVD to a 20 Mb region flanked by D2S2158 and D2S22O2. This region contains 59 genes, of which 20 were sequenced, disclosing a heterozygous mutation (484C > T, R162W) in KCNJ13, member 13 of subfamily J of the potassium inwardly rectifying channel family in all affected individuals. The mutation in KCNJ13, the gene encoding Kir7.1, was not present in unaffected family members and 210 control individuals. Kir7.1 localized to human retina and retinal pigment epithelium and was especially prevalent in the internal limiting membrane adjacent to the vitreous body. Molecular modeling of this mutation predicted disruption of the structure of the potassium channel in the closed state located immediately adjacent to the cell-membrane inner boundary. Functionally, unlike wild-type Kir7.1 whose overexpression in CHO-K1 cells line produces highly selective potassium current, overexpression of R162W mutant Kir7.1 produces a nonselective cation current that depolarizes transfected cells and increases their fragility. These results indicate that the KCNJ13 R162W mutation can cause SVD and further show that vitreoretinal degeneration can arise through mutations in genes whose products are not structural components of the vitreous. C1 [Hejtmancik, J. Fielding; Jiao, Xiaodong; Li, Anren; Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Ding, Xiaoyan; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Ding, Xiaoyan] Sun Yat sen Univ, State Key Lab Ophthalmol 5, Zhongshan Ophthalm Ctr, Guangzhou 510060, Peoples R China. [Sharma, Anil K.; Edwards, Albert O.] Mayo Clin, Coll Med, Dept Ophthalmol, Rochester, MN 55905 USA. [Medina, Igor] INMED INSERM, F-13273 Marseille, France. [Medina, Igor] Mediterranean Univ, F-13273 Marseille, France. RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov FU NEI NIH HHS [EY014467, R01 EY014467] NR 29 TC 34 Z9 36 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2008 VL 82 IS 1 BP 174 EP 180 DI 10.1016/j.ajhg.2007.08.002 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 263NM UT WOS:000253223800018 PM 18179896 ER PT J AU Lea, JP Norris, K Agodoa, L AF Lea, Janice P. Norris, Keith Agodoa, Lawrence TI The role of anemia management in improving outcomes for African-Americans with chronic kidney disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Review DE anemia management; diabetes mellitus; hypertension; chronic kidney disease; dialysis ID STAGE RENAL-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; RECEPTOR ACTIVATOR CERA; PERITONEAL-DIALYSIS PATIENTS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; EXTENDED ADMINISTRATION INTERVALS; LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED CONTROLLED-TRIAL; HEMOGLOBIN LEVELS AB Chronic kidney disease (CKD) is a serious threat to African-American public health. In this population CKD progresses to end-stage renal disease (ESRD) at quadruple the rate in Caucasians. Factors fueling progression to ESRD include diabetes and hypertension, which show high prevalences and accelerated renal damage in African-Americans, as well as possible nutritional, socioeconomic, and genetic factors. Anemia, a common and deleterious complication of CKD, is more prevalent and severe in African-American than Caucasian patients at each stage of the disease. Proactive management of diabetes, hypertension, anemia, and other complications throughout the course of CKD can prevent or delay disease progression and alleviate the burden of ESRD for the African-American community. Currently, African-Americans with CKD are less likely than Caucasian patients to receive anemia treatment before and after the onset of dialysis. Although African-Americans often require higher doses of erythropoiesis-stimulating agents, this may result from late treatment initiation, lower hemoglobin levels, or the presence of comorbidities such as diabetes and inflammation, although racial differences in response cannot be excluded. This review explores racial-specific challenges and potential solutions in renal anemia management to improve outcomes in African-American patients. Copyright (C) 2008 S. Karger AG, Basel. C1 [Lea, Janice P.] Emory Univ, Dept Med, Div Renal, Atlanta, GA 30308 USA. [Norris, Keith] Charles R Drew Univ Med & Sci, Clin Res Ctr, Los Angeles, CA 90059 USA. [Norris, Keith] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Agodoa, Lawrence] NIDDK, Chron Kidney Dis Programs, NIH, Bethesda, MD USA. [Agodoa, Lawrence] NIDDK, End Stage Renal Dis Programs, NIH, Bethesda, MD USA. [Agodoa, Lawrence] NIDDK, Off Minor Hlth Res Coordinat, NIH, Bethesda, MD USA. RP Lea, JP (reprint author), Emory Univ, Dept Med, Div Renal, 550 Peachtree St, Atlanta, GA 30308 USA. EM jlea@emory.edu FU NCRR NIH HHS [RR014616, U54 RR014616, U54 RR019234, RR019234, RR011145, P20 RR011145]; NIMHD NIH HHS [MD000182, P20 MD000182] NR 131 TC 10 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2008 VL 28 IS 5 BP 732 EP 743 DI 10.1159/000127981 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 337CJ UT WOS:000258412800005 PM 18434712 ER PT J AU Bradley, CS Kenton, KS Richter, HE Gao, X Zyczynski, HM Weber, AM Nygaard, IE AF Bradley, Catherine S. Kenton, Kimberly S. Richter, Holly E. Gao, Xin Zyczynski, Halina M. Weber, Anne M. Nygaard, Ingrid E. CA Pelvic Floor Disorders Network TI Obesity and outcomes after sacrocolpopexy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 14-16, 2008 CL Savannah, GA SP Soc Gynecol Surg DE abdominal sacrocolpopexy; obesity; postoperative complications; surgical outcomes ID PELVIC ORGAN PROLAPSE; BODY-MASS INDEX; URINARY STRESS-INCONTINENCE; FREE VAGINAL TAPE; BURCH COLPOSUSPENSION; FLOOR DISORDERS; WOMEN; SURGERY; HEALTH; RISK AB OBJECTIVE: The purpose of this study was to compare outcomes after sacrocolpopexy (SC) between obese and healthy-weight women. STUDY DESIGN: Baseline and postoperative data were analyzed from the Colpopexy And Urinary Reduction Efforts (CARE) randomized trial of SC with or without Burch colposuspension in stress continent women with stages II-IV prolapse. Outcomes and complications were compared between obese and healthy-weight women. RESULTS: CARE participants included 74 obese (body mass index >= 30 kg/m(2)), 122 overweight (25-29.9 kg/m2), and 125 healthy-weight (18.5-24.9 kg/m2) women, and 1 underweight (< 18.5 kg/m2) woman. Compared to healthy-weight women, obese women were younger (59.0 +/- 9.9 vs 62.1 +/- 10.3 yrs; P = .04), more likely to have stage II prolapse (25.7% vs 11.2%; P = .01), and had longer operative times (189 +/- 52 vs 169 +/- 58 min; P = .02). Two years after surgery, stress incontinence, prolapse, symptom resolution, and satisfaction did not differ between the obese and healthy-weight groups. CONCLUSION: Most outcomes and complication rates after SC are similar in obese and healthy-weight women. C1 [Bradley, Catherine S.] Univ Iowa, Dept Obstet & Gynecol, Carver Coll Med, Iowa City, IA 52242 USA. [Kenton, Kimberly S.] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. [Kenton, Kimberly S.] Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA. [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL USA. [Gao, Xin] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Zyczynski, Halina M.] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. [Weber, Anne M.] NICHHD, NIH, Bethesda, MD 20892 USA. [Nygaard, Ingrid E.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. RP Bradley, CS (reprint author), Univ Iowa, Dept Obstet & Gynecol, Carver Coll Med, Iowa City, IA 52242 USA. FU NICHD NIH HHS [U10 HD041248, U01 HD041249, U01 HD041249-08, U01 HD41249, U10 HD041250, U10 HD041261, U10 HD041263, U10 HD041267, U10 HD041268, U10 HD041269, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269] NR 27 TC 8 Z9 8 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PY 2008 VL 199 IS 6 AR 690.e1 DI 10.1016/j.ajog.2008.07.030 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 383PZ UT WOS:000261687000040 PM 18845288 ER PT J AU Bytautiene, E Vedernikov, YP Maner, WL Saade, GR Romero, R Garfield, RE AF Bytautiene, Egle Vedernikov, Yuri P. Maner, William L. Saade, George R. Romero, Roberto Garfield, Robert E. TI Challenge with ovalbumin antigen increases uterine and cervical contractile activity in sensitized guinea pigs SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervix; contractility; guinea pig; type I hypersensitivity reaction; uterus ID NONPREGNANT HUMAN UTERUS; MAST-CELLS; HUMAN MYOMETRIUM; PREGNANT-WOMEN; HISTAMINE; MEDIATORS; LABOR; DEGRANULATION; MUSCLE; RATS AB OBJECTIVE: The aims of this study were to investigate the effects of ovalbumin challenge on uterine and cervical contractility, intrauterine pressure, and uterine electromyography activity in sensitized guinea pigs. STUDY DESIGN: Guinea pigs were sensitized by injection of ovalbumin-aluminum hydroxide suspension. Control animals were injected with the aluminum hydroxide suspension only. On days 55-57 of pregnancy, longitudinal uterine and cervical strips from guinea pigs were prepared for isometric tension recording. Nonpregnant guinea pigs were outfitted with telemetric transducers to record intrauterine pressure and uterine electromyography. RESULTS: Ovalbumin significantly increased contractility of uterine and cervical strips from sensitized versus nonsensitized animals. These effects were abolished by histamine H(1) receptor antagonist in uterine strips and by histamine H(1) receptor antagonist and a mast cell stabilizer in cervical strips from sensitized animals. Cyclooxygenase and 5-lipoxygenase inhibitors had no significant effect on the response to ovalbumin. Treatment with ovalbumin in vivo significantly increased intrauterine pressure and uterine electromyography activity in sensitized but not in nonsensitized, animals. CONCLUSION: Our findings indicate that type I hypersensitivity reactions may be important in mediating uterine contractility in pregnant and nonpregnant states. C1 [Bytautiene, Egle; Vedernikov, Yuri P.; Maner, William L.; Saade, George R.; Garfield, Robert E.] Univ Texas Galveston, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Bytautiene, E (reprint author), Univ Texas Galveston, Med Branch, Dept Obstet & Gynecol, 301 Univ Blvd,Rt 1062, Galveston, TX 77555 USA. EM ebytaut@utmb.edu FU Intramural NIH HHS NR 35 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PY 2008 VL 199 IS 6 AR 658.e1 DI 10.1016/j.ajog.2008.06.036 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 383PZ UT WOS:000261687000026 PM 18722575 ER PT J AU Saadani-Makki, F Kannan, S Lu, X Janisse, J Dawe, E Edwin, S Romero, R Chugani, D AF Saadani-Makki, Fadoua Kannan, Sujatha Lu, Xin Janisse, James Dawe, Elizabeth Edwin, Samuel Romero, Roberto Chugani, Diane TI Intrauterine administration of endotoxin leads to motor deficits in a rabbit model: a link between prenatal infection and cerebral palsy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-for-Neuroscience CY NOV 03-07, 2007 CL San Diego, CA SP Soc Neurosci DE cerebral palsy; intrauterine inflammation; microglia; perinatal brain injury ID C-REACTIVE PROTEIN; LATE OLIGODENDROCYTE PROGENITORS; WHITE-MATTER; PLASMA INTERLEUKIN-6; HUMAN HEPATOCYTES; PERINATAL RABBIT; HYPOXIA-ISCHEMIA; PRETERM INFANTS; BRAIN; INJURY AB OBJECTIVE: This study was undertaken to determine whether maternal intrauterine endotoxin administration leads to neurobehavioral deficits in newborn rabbits. STUDY DESIGN: Pregnant New Zealand white rabbits were injected with 1 mL saline solution ( n = 8) or 20 mu g/kg of lipopolysaccharide in saline solution ( n = 8) into the uterine wall on day 28/31 of gestation. On postnatal day 1, kits ( saline solution [ n = 30] and lipolysaccharide in saline solution [ n = 18] from 4 consecutive litters) underwent neurobehavioral testing. Neonatal brains were stained for microglial cells and myelin. RESULTS: Kits in the lipopolysaccharide in saline solution group were hypertonic and demonstrated significant impairment in posture, righting reflex, locomotion, and feeding, along with neuroinflammation indicated by activated microglia and hypomyelination in the periventricular regions. A greater mortality was noted in the lipopolysaccharide in saline solution group ( 16 stillbirths from 3 litters vs 3 from 1 litter). CONCLUSION: Maternal intrauterine endotoxin administration leads to white matter injury and motor deficits in the newborn rabbit, resulting in a phenotype that resembles those found in periventricular leukomalacia and cerebral palsy. C1 [Saadani-Makki, Fadoua; Kannan, Sujatha; Lu, Xin; Chugani, Diane] Wayne State Univ, Sch Med, Carman & Ann Adams Dept Pediat, Detroit, MI USA. [Janisse, James] Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. [Dawe, Elizabeth] Wayne State Univ, Sch Med, Surg Res Serv, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Sch Med, Dept Med & Mol Genet, Detroit, MI USA. [Chugani, Diane] Wayne State Univ, Sch Med, Dept Radiol, Detroit, MI USA. [Edwin, Samuel; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Kannan, S (reprint author), Childrens Hosp Michigan, Carman & Ann Adams Dept Pediat, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM skannan@med.wayne.edu FU Intramural NIH HHS; NICHD NIH HHS [K08 HD050652-02, K08 HD050652, K08 HD050652-03] NR 39 TC 13 Z9 13 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PY 2008 VL 199 IS 6 AR 651.e1 DI 10.1016/j.ajog.2008.06.090 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 383PZ UT WOS:000261687000023 PM 18845289 ER PT J AU Troisi, R Braekke, K Harsem, NK Hyer, M Hoover, RN Staff, AC AF Troisi, Rebecca Braekke, Kristin Harsem, Nina Kittelsen Hyer, Marianne Hoover, Robert N. Staff, Anne Cathrine TI Blood pressure augmentation and maternal circulating concentrations of angiogenic factors at delivery in preeclamptic and uncomplicated pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE angiogenic factors; blood pressure; breast cancer; preeclampsia; pregnancy ID HUMAN BREAST-CANCER; CARDIOVASCULAR-DISEASE; INFLAMMATORY RESPONSE; SOLUBLE ENDOGLIN; SUBSEQUENT RISK; WOMEN; SERUM; SFLT1; HYPERTENSION; ENDOSTATIN AB OBJECTIVE: The objective of the study was to determine whether blood pressure increases are associated with maternal angiogenic factors in uncomplicated and preeclamptic pregnancies. STUDY DESIGN: Associations of blood pressure increases from mid-to late pregnancy with maternal serum concentrations of soluble fms-like tyrosine kinase receptor ( sFlt1), soluble endoglin ( sEng), and placental growth factor ( PlGF) at delivery were analyzed in 43 uncomplicated and 44 preeclamptic pregnancies. RESULTS: In uncomplicated pregnancies, increases in diastolic and mean arterial pressure were inversely associated with PlGF at delivery and positively associated with sEng and sFlt1/PlGF ratio. There were no significant associations between blood pressure increases and angiogenic factor concentrations in preeclampsia. CONCLUSION: These data suggest that angiogenic factors are involved in blood pressure modulation in normotensive pregnancy and are consistent with the hypothesis that angiogenic balance plays a role in maternal breast cancer risk reduction associated with mid-to late blood pressure increases in uncomplicated pregnancies. C1 [Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Troisi, Rebecca] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [Braekke, Kristin] Ullevaal Univ Hosp, Dept Pediat, Oslo, Norway. [Harsem, Nina Kittelsen; Staff, Anne Cathrine] Ullevaal Univ Hosp, Dept Obstet & Gynecol, Oslo, Norway. [Staff, Anne Cathrine] Univ Oslo, Fac Med, Oslo, Norway. [Hyer, Marianne] Informat Management Serv Inc, Rockville, MD USA. RP Troisi, R (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. FU Vitenskapsradet Ulleval universitetssykehus; Woman and Child Division, Ulleval University Hospital; Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health; US Department of Health and Human Services FX This study was supported by grants from Vitenskapsradet Ulleval universitetssykehus and the Woman and Child Division, Ulleval University Hospital. The Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, and US Department of Health and Human Services also provided funding. NR 27 TC 6 Z9 7 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PY 2008 VL 199 IS 6 AR 653.e1 DI 10.1016/j.ajog.2008.06.030 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 383PZ UT WOS:000261687000024 PM 18722574 ER PT J AU Romero, R Garite, TJ AF Romero, Roberto Garite, Thomas J. TI Twenty percent of very preterm neonates (23-32 weeks of gestation) are born with bacteremia caused by genital Mycoplasmas SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article ID LOW-BIRTH-WEIGHT; CHRONIC LUNG-DISEASE; UREAPLASMA-UREALYTICUM COLONIZATION; POLYMERASE-CHAIN-REACTION; MIDTRIMESTER AMNIOTIC-FLUID; WHITE-MATTER LESIONS; CLINICAL-SIGNIFICANCE; MICROBIAL INVASION; INTRAAMNIOTIC INFECTION; INTRAUTERINE INFECTION C1 [Romero, Roberto; Garite, Thomas J.] Wayne State Univ, NICHD NIH DHHS, Div INtramural Res, Program Director Obstet & Perinatol,Perinatol Res, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, NICHD NIH DHHS, Div INtramural Res, Program Director Obstet & Perinatol,Perinatol Res, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov FU Intramural NIH HHS NR 68 TC 39 Z9 41 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2008 VL 198 IS 1 BP 1 EP 3 DI 10.1016/j.ajog.2007.11.031 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249YY UT WOS:000252268400001 PM 18166295 ER PT J AU Conde-Agudelo, A Villar, J Lindheimer, M AF Conde-Agudelo, Agustin Villar, Jose Lindheimer, Marshall TI Maternal infection and risk of preeclampsia: Systematic review and metaanalysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE maternal infection; periodontal disease; preeclampsia; urinary tract infection ID INTRAUTERINE GROWTH RESTRICTION; EARLY-ONSET PREECLAMPSIA; CHLAMYDIA-PNEUMONIAE; PERIODONTAL-DISEASE; PREGNANT-WOMEN; ASYMPTOMATIC BACTERIURIA; ANTIRETROVIRAL THERAPY; HYPERTENSIVE DISORDERS; PLACENTAL MALARIA; PRETERM BIRTH AB There are lingering questions regarding the association between maternal infection and preeclampsia. Systematic review and metaanalysis was conducted of observational studies that examined the relationship between maternal infection and preeclampsia. Forty-nine studies met the inclusion criteria. The risk of preeclampsia was increased in pregnant women with urinary tract infection (pooled odds ratio, 1.57; 95% Cl, 1.45-1.70) and periodontal disease (pooled odds ratio, 1.76; 95% Cl, 1.43-2.18). There were no associations between preeclampsia and presence of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus, treated and nontreated HIV infection, and malaria. Individual studies did not find a relationship between herpes simplex virus type 2, bacterial vaginosis, and Mycoplasma hominis and preeclampsia. Urinary tract infection and periodontal disease during pregnancy are associated with an increased risk of preeclampsia. More studies are required to verify this as well as to explore whether or not such relationships are causal and, if so, the mechanisms involved. C1 [Conde-Agudelo, Agustin] NICHD NIH DHHS, Perinatol Res Branch, Intramural Div, Baltimore, MD USA. [Villar, Jose] Univ Oxford, Dept Obstet & Gynecol, Oxford, England. [Lindheimer, Marshall] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Conde-Agudelo, A (reprint author), NICHD NIH DHHS, Perinatol Res Branch, Intramural Div, Baltimore, MD USA. NR 80 TC 118 Z9 124 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2008 VL 198 IS 1 BP 7 EP 22 DI 10.1016/j.ajog.2007.07.040 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249YY UT WOS:000252268400003 PM 18166297 ER PT J AU Klebanoff, MA AF Klebanoff, Mark A. TI Paternal and maternal birthweights and the risk of infant preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Pediatric-and-Perinatal-Epidemiologic-Research CY JUN 18-19, 2007 CL Boston, MA SP Soc Pediat & Perinatal Epidemiol Res DE birthweight; genetics; paternal effects ID GENERATIONS; LENGTH; AGE AB OBJECTIVE: Increasing paternal birthweight has been associated with increased risk of fathering a preterm infant, causing speculation that a fetus programmed to grow rapidly can trigger preterm labor. STUDY DESIGN: Pregnancies occurring from 1974-1989 among women themselves born in the Danish Perinatal Study (1959-1961) were identified through the Population Register; obstetric records were abstracted. Paternal birthweight was obtained by linking Personal Identification Numbers of the fathers to archived midwifery records. RESULTS: Paternal birthweight was not associated with preterm infants overall. However, there was a significant interaction between paternal and maternal birthweights ( P = .003). When the mother weighed less than 3 kg at birth, increasing paternal birthweight was associated with increased occurrence of preterm birth (P for trend = .02); paternal birthweight was unassociated with preterm birth for mothers weighing 3 kg or more at birth (P = .34). CONCLUSION: When the mother was born small, increasing paternal birthweight was associated with increased risk of preterm birth, suggesting that a fetus growing faster than its mother can accommodate might trigger preterm birth. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Klebanoff, MA (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. FU Intramural NIH HHS [NIH0010045861]; NICHD NIH HHS [N01-HD-7-2902]; PHS HHS [NIH0010045861] NR 8 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 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2008 VL 198 IS 1 AR 58.e1 DI 10.1016/j.ajog.2007.06.013 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249YY UT WOS:000252268400019 PM 18166307 ER PT J AU Romero, R Schaudinn, C Kusanovic, JP Gorur, A Gotsch, F Webster, P Nhan-Chang, CL Erez, O Kim, CJ Espinoza, J Goncalves, LF Vaisbuch, E Mazaki-Tovi, S Hassan, SS Costerton, JW AF Romero, Roberto Schaudinn, Christoph Kusanovic, Juan Pedro Gorur, Amita Gotsch, Francesca Webster, Paul Nhan-Chang, Chia-Ling Erez, Offer Kim, Chong Jai Espinoza, Jimmy Goncalves, Luis F. Vaisbuch, Edi Mazaki-Tovi, Shali Hassan, Sonia S. Costerton, J. William TI Detection of a microbial biofilm in intraamniotic infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE amniocentesis; amniotic fluid sludge; clinical chorioamnionitis; intraamniotic infection; microbial invasion of the amniotic cavity; preterm labor ID POLYMERASE-CHAIN-REACTION; AMNIOTIC-FLUID SLUDGE; INFLAMMATORY RESPONSE SYNDROME; UREAPLASMA-UREALYTICUM; CLINICAL-SIGNIFICANCE; PRETERM LABOR; ANTIBIOTIC-RESISTANCE; MYCOPLASMA-HOMINIS; SUBGINGIVAL PLAQUE; BACTERIAL BIOFILMS AB OBJECTIVE: Microbial biofilms are communities of sessile microorganisms formed by cells that are attached irreversibly to a substratum or interface or to each other and embedded in a hydrated matrix of extracellular polymeric substances. Microbial biofilms have been implicated in > 80% of human infections such as periodontitis, urethritis, endocarditis, and device-associated infections. Thus far, intraamniotic infection has been attributed to planktonic (free-floating) bacteria. A case is presented in which "amniotic fluid sludge" was found to contain microbial biofilms. This represents the first report of a microbial biofilm in the amniotic cavity. STUDY DESIGN: "Amniotic fluid sludge" was detected by transvaginal sonography and retrieved by transvaginal amniotomy. Bacteria were identified with scanning electron microscopy and fluorescence in situ hybridization for conserved regions of the microbial genome; the exopolymeric matrix was identified by histochemistry by the wheat germ confocal laser scanning microscopy. RESULTS: "Amniotic fluid sludge" was imaged with scanning electron microscopy, which allowed the identification of bacteria embedded in an amorphous material and inflammatory cells. Bacteria were demonstrated with fluorescent in situ hybridization using a eubacteria probe. Extracellular matrix was identified with the wheat germ agglutinin lectin stain. Confocal microscopy allowed 3-dimensional visualization of the microbial biofilm. CONCLUSION: Microbial biofilms have been identified in a case of intraamniotic infection with "amniotic fluid sludge.". C1 [Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Nhan-Chang, Chia-Ling; Kim, Chong Jai; Espinoza, Jimmy; Goncalves, Luis F.; Vaisbuch, Edi; Mazaki-Tovi, Shali; Hassan, Sonia S.] Wayne State Univ, Perinatol Res Branch, NICHD,NIH,DHHS, Hutzel Womens Hosp, Detroit, MI 48201 USA. [Romero, Roberto; Kusanovic, Juan Pedro; Nhan-Chang, Chia-Ling; Erez, Offer; Espinoza, Jimmy; Goncalves, Luis F.; Vaisbuch, Edi; Mazaki-Tovi, Shali; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Kim, Chong Jai] Wayne State Univ, Hutzel Womens Hosp, Dept Pathol, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Schaudinn, Christoph; Gorur, Amita; Costerton, J. William] Univ So Calif, Sch Dent, Ctr Biofilm, Los Angeles, CA 90089 USA. [Webster, Paul] House Ear Res Inst, Los Angeles, CA USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD,NIH,DHHS, Hutzel Womens Hosp, 3990 John Rbox 4, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural NIH HHS [Z01 HD002400-16] NR 33 TC 6 Z9 14 U1 0 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2008 VL 198 IS 1 AR 135.e1 DI 10.1016/j.ajog.2007.11.026 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249YY UT WOS:000252268400053 PM 18166328 ER PT J AU Simhan, HN Chiao, JP Mattison, DR Caritis, SN AF Simhan, Hyagriv N. Chiao, Jye-Ping Mattison, Donald R. Caritis, Steve N. TI Human decidual cell Toll-like receptor signaling in response to endotoxin: The effect of progestins SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE decidual cell; progesterone; progestin; Toll-like receptor ID PRETERM BIRTH; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; INTERLEUKIN-8 PRODUCTION; PROGESTERONE; WOMEN; RISK; RECOGNITION; ACTIVATION; EXPRESSION; INTERFACE AB OBJECTIVE: The purpose of this study was to determine whether progesterone, 17-alpha-hydroxyprogesterone, and 17-alpha hydroxyprogesterone caproate modulate the Toll-like receptor (TLR) pathway in the response of decidua to lipopolysaccharide. STUDY DESIGN: Cultured human decidual cells were incubated under control conditions, lipopolysaccharide alone, or pretreatment with each of the 3 progestins. Relative expression of 113 genes in the TLR pathway was determined by microarray. RESULTS: We failed to demonstrate a suppression of TLR gene pathway expression in human decidual cells in response to lipopolysaccharide when the cells are pretreated with progestins. Pretreatment with each progestin before lipopolysaccharide resulted in a relative increase in the expression of the proapoptotic molecule, CASP8. There were no differences among the progestins. CONCLUSION: Our data do not support suppression of TLR pathways as a mechanism for the benefit of 17-alpha hydroxyprogesterone caproate. Increased CASP8 gene expression raises the possibility that progestins "prime" the decidual cell to respond with a NF kappa B-mediated inflammatory response. C1 [Simhan, Hyagriv N.; Chiao, Jye-Ping; Caritis, Steve N.] Univ Pittsburgh, Sch Med, Magee Womens Res Inst, Div Maternal Fetal Med, Pittsburgh, PA 15260 USA. [Simhan, Hyagriv N.] Univ Pittsburgh, Sch Med, Magee Womens Res Inst, Div Reprod Infect Dis & Immunol,Dept Obstet Gynec, Pittsburgh, PA USA. [Mattison, Donald R.] Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD USA. RP Simhan, HN (reprint author), Univ Pittsburgh, Sch Med, Magee Womens Res Inst, Div Maternal Fetal Med, Pittsburgh, PA 15260 USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; caritis, steve/0000-0002-2169-0712 FU NCATS NIH HHS [UL1 TR000005]; NICHD NIH HHS [1 R01 HD052732-01, 5U10 HD047905-02, R01 HD052732, U10 HD047905, U10 HD047905-05] NR 24 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2008 VL 198 IS 1 AR 119.e1 DI 10.1016/j.ajog.2007.06.022 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249YY UT WOS:000252268400046 PM 17936235 ER PT J AU Schwandt, ML Newman, TK Lindell, SG Higley, JD Goldman, D Barr, CS AF Schwandt, M. L. Newman, T. K. Lindell, S. G. Higley, J. D. Goldman, D. Barr, C. S. TI Monoamine oxidase A (MAOA) gene promoter variation influences aggressive behavior towards an unfamiliar intruder in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 77th Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-12, 2008 CL Columbus, OH SP Amer Assoc Phys Anthropol C1 [Schwandt, M. L.; Lindell, S. G.; Barr, C. S.] NIAAA, Natl Inst Hlth, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Goldman, D.; Barr, C. S.] NIAAA, Neurogenet Lab, Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2008 SU 46 BP 189 EP 189 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 265EN UT WOS:000253342000581 ER PT J AU Uddin, M Goodman, M Sherwood, CC Starzl, TE Grossman, LI Romero, R Wildman, DE AF Uddin, M. Goodman, M. Sherwood, C. C. Starzl, T. E. Grossman, L. I. Romero, R. Wildman, D. E. TI Distinct genomic signatures of adaptation in pre- and post-natal environments during human evolution. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 77th Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-12, 2008 CL Columbus, OH SP Amer Assoc Phys Anthropol C1 [Uddin, M.; Goodman, M.; Grossman, L. I.; Wildman, D. E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48202 USA. [Goodman, M.] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48202 USA. [Sherwood, C. C.] George Washington Univ, Dept Anthropol, Washington, DC 20052 USA. [Starzl, T. E.] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15260 USA. [Romero, R.; Wildman, D. E.] NIH, Natl Inst Child Hlth & Dev, Perinatol Res Branch, Bethesda, MD 20892 USA. [Wildman, D. E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. 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 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2008 SU 46 BP 211 EP 211 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 265EN UT WOS:000253342000679 ER PT J AU Muniyappa, R Lee, S Chen, H Quon, MJ AF Muniyappa, Ranganath Lee, Sihoon Chen, Hui Quon, Michael J. TI Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE glucose clamp; quantitative insulin sensitivity check index; minimal model; homeostatis model assessment ID HOMEOSTASIS MODEL ASSESSMENT; GLUCOSE-TOLERANCE TEST; BETA-CELL FUNCTION; DEPENDENT DIABETES-MELLITUS; FASTING PLASMA-GLUCOSE; MINIMAL-MODEL; SKELETAL-MUSCLE; CHECK INDEX; CARDIOVASCULAR-DISEASE; SOMATOSTATIN INFUSION AB Insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases. Therefore, quantifying insulin sensitivity/resistance in humans and animal models is of great importance for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice. Direct and indirect methods of varying complexity are currently employed for these purposes. Some methods rely on steady-state analysis of glucose and insulin, whereas others rely on dynamic testing. Each of these methods has distinct advantages and limitations. Thus, optimal choice and employment of a specific method depends on the nature of the studies being performed. Established direct methods for measuring insulin sensitivity in vivo are relatively complex. The hyperinsulinemic euglycemic glucose clamp and the insulin suppression test directly assess insulin-mediated glucose utilization under steady-state conditions that are both labor and time intensive. A slightly less complex indirect method relies on minimal model analysis of a frequently sampled intravenous glucose tolerance test. Finally, simple surrogate indexes for insulin sensitivity/resistance are available (e. g., QUICKI, HOMA, 1/insulin, Matusda index) that are derived from blood insulin and glucose concentrations under fasting conditions (steady state) or after an oral glucose load (dynamic). In particular, the quantitative insulin sensitivity check index (QUICKI) has been validated extensively against the reference standard glucose clamp method. QUICKI is a simple, robust, accurate, reproducible method that appropriately predicts changes in insulin sensitivity after therapeutic interventions as well as the onset of diabetes. In this Frontiers article, we highlight merits, limitations, and appropriate use of current in vivo measures of insulin sensitivity/resistance. C1 [Muniyappa, Ranganath; Lee, Sihoon; Chen, Hui; Quon, Michael J.] NCCAM, NIH, Diabet Unit, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NCCAM, NIH, Diabet Unit, 9 Mem Dr,Bldg 9,Rm 1N-105,MSC 0920, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS NR 104 TC 546 Z9 576 U1 7 U2 70 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2008 VL 294 IS 1 BP E15 EP E26 DI 10.1152/ajpendo.00645.2007 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 250LZ UT WOS:000252302900003 PM 17957034 ER PT J AU Kagawa, T Watanabe, N Mochizuki, K Numari, A Ikeno, Y Itoh, J Tanaka, H Arias, IM Mine, T AF Kagawa, Tatehiro Watanabe, Norihito Mochizuki, Kaori Numari, Asano Ikeno, Yoshie Itoh, Johbu Tanaka, Hirotoshi Arias, Irwin M. Mine, Tetsuya TI Phenotypic differences in PFIC2 and BRIC2 correlate with protein stability of mutant Bsep and impaired taurocholate secretion in MDCK II cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE bile salt export pump; bile secretion; cholestasis; ABCB11; mutation ID SALT EXPORT PUMP; FAMILIAL INTRAHEPATIC CHOLESTASIS; TRANSMEMBRANE CONDUCTANCE REGULATOR; RESISTANCE-ASSOCIATED PROTEIN-2; CANALICULAR MEMBRANE-VESICLES; BILE-ACID SECRETION; RAT-LIVER; ABC TRANSPORTERS; APICAL MEMBRANE; CYSTIC-FIBROSIS AB Progressive familial cholestasis (PFIC) 2 and benign recurrent intrahepatic cholestasis (BRIC) 2 are caused by mutations in the bile salt export pump (BSEP, ABCB11) gene; however, their prognosis differs. PFIC2 progresses to cirrhosis and requires liver transplantation, whereas BRIC2 is clinically benign. To identify the molecular mechanism(s) responsible for the phenotypic differences, eight PFIC2 and two BRIC2 mutations were introduced in rat Bsep, which was transfected in MDCK II cells. Taurocholate transport activity, protein expression, and subcellular distribution of these mutant proteins were studied in a polarized MDCK II monolayer. The taurocholate transport activity was approximately half of the wild-type (WT) in BRIC2 mutants (A570T and R1050C), was substantially less in two PFIC2 mutants (D482G and E297G), and was almost abolished in six other PFIC2 mutants (K461E, G982R, R1153C, R1268Q, 3767-3768insC, and R1057X). Bsep protein expression levels correlated closely with transport activity, except for R1057X. The half-life of the D482G mutant was shorter than that of the WT (1.35 h vs. 3.49 h in the mature form). BRIC2 mutants and three PFIC mutants (D482G, E297G, and R1057X) were predominantly distributed in the apical membrane. The other PFIC2 mutants remained intracellular. The R1057X mutant protein was stably expressed and trafficked to the apical membrane, suggesting that the COOH-terminal tail is required for transport activity but not for correct targeting. In conclusion, taurocholate transport function was impaired in proportion to rapid degradation of Bsep protein in the mutants, which were aligned in the following order: A570T and R1050C > D482G > E297G > K461E, G982R, R1153C, R1268Q, 3767 - 3768insC, and R1057X. These results may explain the phenotypic difference between BRIC2 and PFIC2. C1 [Kagawa, Tatehiro; Watanabe, Norihito; Mochizuki, Kaori; Numari, Asano; Ikeno, Yoshie; Mine, Tetsuya] Tokai Univ, Sch Med, Dept Internal Med, Div Gastroenterol, Kanagawa 2591193, Japan. [Itoh, Johbu] Tokai Univ, Sch Med, Labs Struct & Funct Res, Kanagawa 2591193, Japan. [Tanaka, Hirotoshi] Univ Tokyo, Inst Med Sci, Dept Rheumatol & Allergy, Minato Ku, Tokyo, Japan. [Arias, Irwin M.] Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. [Arias, Irwin M.] NICHHD, Bethesda, MD 20892 USA. [Arias, Irwin M.] NIH, Unit Cellular Polar, Bethesda, MD 20892 USA. RP Kagawa, T (reprint author), Tokai Univ, Sch Med, Dept Internal Med, Div Gastroenterol, Kanagawa 2591193, Japan. EM kagawa@is.icc.u-tokai.ac.jp FU NIDDK NIH HHS [DK-54785, DK-35652] NR 44 TC 31 Z9 31 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 2008 VL 294 IS 1 BP G58 EP G67 DI 10.1152/ajpgi.00367.2007 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 252RP UT WOS:000252464600008 PM 17947449 ER PT J AU Wecht, JM Weir, JP Goldstein, DS Krothe-Petroff, A Spungen, AM Holmes, C Bauman, WA AF Wecht, Jill M. Weir, Joseph P. Goldstein, David S. Krothe-Petroff, Annmarie Spungen, Ann M. Holmes, Courtney Bauman, William A. TI Direct and reflexive effects of nitric oxide synthase inhibition on blood pressure SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE spinal cord injury; nitro-L-arginine methyl ester; norepinephrine; sympathetic nervous system ID SYMPATHETIC NERVOUS-SYSTEM; CONSCIOUS RATS; L-ARGININE; HUMANS; TONE; HYPERTENSION; TETRAPLEGIA; HYPOTENSION; MUSCLE AB Direct effects of vasoactive substances on blood pressure can be examined in individuals with tetraplegia due to disruption of descending spinal pathways to sympathetic preganglionic neurons, as cervical lesions interfere with baroreceptor reflex buffering of sympathetic outflow. In this study, we assessed effects of the nitric oxide synthase inhibitor nitro-L-arginine methyl ester (L- NAME) on mean arterial pressure, heart rate, and plasma norepinephrine concentrations in individuals with tetraplegia vs. effects shown in a neurologically intact control group. Seven individuals with tetraplegia and seven age-matched controls received, on separate visits and in the following order, placebo (30 ml normal saline) and 0.5, 1, 2, and 4 mg/ kg L- NAME intravenously over 60 min. Supine hemodynamic data were collected, and blood was sampled at the end of each infusion and at 120, 180, and 240 min thereafter. L- NAME increased mean arterial pressure, and the relative increase was greater in the tetraplegia group than in the control group. Heart rate was reduced after L- NAME administration in both groups. L- NAME decreased plasma norepinephrine in the control group but not in the group with tetraplegia. These findings suggest that reflexive sympathoinhibition normally buffers the pressor response to nitric oxide synthase inhibition, an effect that is not evident in individuals with tetraplegia as a result of decentralized sympathetic vasomotor control. C1 [Wecht, Jill M.] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Mt Sinai Hosp, Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Mt Sinai Hosp, Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. [Weir, Joseph P.] Des Moines Univ Osteopath Med Ctr, Des Moines, IA USA. [Goldstein, David S.; Holmes, Courtney] Natl Inst Neurol Disorders & Stroke, NIH, Div Intramural Res, Clin Neurosci Program,Clin Neurocardiol Sect, Bethesda, MD USA. RP Wecht, JM (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Rm 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM jm.wecht@va.gov FU Intramural NIH HHS NR 30 TC 12 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2008 VL 294 IS 1 BP H190 EP H197 DI 10.1152/ajpheart.00366.2007 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 249WO UT WOS:000252261200023 PM 17965289 ER PT J AU Canales, MK Breslau, ES Nelson, DE Ballard-Barbash, RR AF Canales, Mary K. Breslau, Erica S. Nelson, David E. Ballard-Barbash, Rachel R. TI Did news reporters get it right? Translation of the 2002 hormone study findings SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; REPLACEMENT THERAPY; PRESS RELEASES; MEDIA; BENEFITS; COVERAGE; STORIES; RISKS AB Background: The news media play a critical role in communicating health information to the public. The unexpected findings in July 2002 about increased health risks associated with hormone therapy provided an opportunity to examine the process of translating scientific findings to reporters through communication intermediaries and appraise subsequent reporting in newspapers in the United States. Methods: Using qualitative research software, a qualitative analysis was conducted in 2006 to consider four types of messages: (1) hormone therapy health risks outweighed benefits (balance); (2) adverse hormone therapy health outcomes (health risk); (3) positive hormone therapy health outcomes (benefit); and (4) risk level (magnitude). The print materials analyzed included the original 2002 Journal of American Medical Association (JAMA) article and editorial; JAMA and National Institutes of Health (NIH) press releases; the NIH press conference transcript; and 198 articles about hormone therapy in 22 U.S. newspapers published from July to September 2002. Results: The major study finding that hormone therapy risks outweighed benefits was reported consistently and accurately. Analyses of language and numbers on risk magnitude, and its interpretation revealed some variability, both within the translation materials and news stories. When risk numbers were included in newspaper stories, absolute risk was used more often than relative risk. Conclusions: Despite much criticism of journalists' coverage of health issues, U.S. newspaper reporting about hormone therapy in 2002 was generally consistent. Several translational and communication strategies used with hormone therapy may be applicable to other efforts that involve working with reporters on major health stories or events. An important process oversight was the absence of hormone therapy communication efforts and guidance directed specifically to medical practitioners. C1 [Canales, Mary K.] Canc Educ Grants Dept, Mashantucket Pequot Tribal Nat, Bemidji, MN USA. [Breslau, Erica S.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ballard-Barbash, Rachel R.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Nelson, David E.] Ctr Dis Control & Prevent, Hlth Commun Branch, Off Smoking & Hlth, Atlanta, GA USA. RP Canales, MK (reprint author), 215 Pine Grove St SW, Bemidji, MN 56601 USA. EM mkcanales@charter.net NR 39 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2008 VL 34 IS 1 BP 61 EP 68 DI 10.1016/j.amepre.2007.09.023 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 246BY UT WOS:000251983700009 PM 18083452 ER PT J AU Lissek, S Levenson, J Biggs, AL Johnson, LL Arneli, R Pine, DS Grillon, C AF Lissek, Shmuel Levenson, Jessica Biggs, Arter L. Johnson, Linda L. Arneli, Rezvan Pine, Daniel S. Grillon, Christian TI Elevated fear conditioning to socially relevant unconditioned stimuli in social anxiety disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 27th Annual Conference of the Anxiety-Disorders-Association-of-America CY MAR 29-APR 01, 2007 CL St Louis, MO SP Anxiety Disorders Assoc Amer ID POTENTIATED STARTLE; US INTENSITY; PHOBIA; STRESS; HUMANS; ACQUISITION; ACTIVATION; AWARENESS; RESPONSES; ETIOLOGY AB Objective: Though conditioned fear has long been acknowledged as an important etiologic mechanism in social anxiety disorder, past psychophysiological experiments have found no differences in general conditionability among social anxiety patients using generally aversive but socially nonspecific unconditioned stimuli (e.g., unpleasant odors and painful pressure). The authors applied a novel fear conditioning paradigm consisting of socially relevant unconditioned stimuli of critical facial expressions and verbal feedback. This study represents the first effort to assess the conditioning correlates of social anxiety disorder within an ecologically enhanced paradigm. Method: Subjects with social anxiety disorder and age- and gender-matched healthy comparison subjects underwent differential classical conditioning. Conditioned stimuli included images of three neutral facial expressions, each of which was paired with one of three audiovisual unconditioned stimuli: negative insults with critical faces (USneg), positive compliments with happy faces (USpos), or neutral comments with neutral faces (USneu). The conditioned response was measured as the fear-potentiation of the startle-blink reflex elicited during presentation of the conditioned stimuli. Results: Only social anxiety subjects demonstrated fear conditioning in response to facial expressions, as the startle-blink reflex was potentiated by the CSneg versus both CSneu and CSpos among those with the disorder, while healthy comparison subjects displayed no evidence of conditioned startle-potentiation. Such group differences in conditioning were independent of levels of anxiety to the unconditioned stimulus, implicating associative processes rather than increased unconditioned stimulus reactivity as the active mechanism underlying enhanced conditioned startle-potentiation among social anxiety subjects. Conclusions: Results support a conditioning contribution to social anxiety disorder and underscore the importance of disorder-relevant unconditioned stimuli when studying the conditioning correlates of pathologic anxiety. C1 [Lissek, Shmuel] NIMH, NIH, Bethesda, MD 20892 USA. RP Lissek, S (reprint author), NIMH, NIH, 15K N Dr,Rm 200, Bethesda, MD 20892 USA. EM lisseks@mail.nih.gov RI Lissek, Shmuel/B-6577-2008; Levenson, Jessica/O-5448-2015 FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [MH-002798-06, Z01 MH002798] NR 40 TC 59 Z9 60 U1 4 U2 20 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2008 VL 165 IS 1 BP 124 EP 132 PG 9 WC Psychiatry SC Psychiatry GA 248VU UT WOS:000252186000022 PM 18006874 ER PT J AU Brown, TM Fee, E AF Brown, Theodore M. Fee, Elizabeth TI Spinning for India's independence SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. [Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM theodore_brown@urmc.rochester.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2008 VL 98 IS 1 BP 39 EP 39 DI 10.2105/AJPH.2007.120139 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 248TJ UT WOS:000252178200012 PM 18048775 ER PT J AU Brown, TM Fee, E AF Brown, Theodore M. Fee, Elizabeth TI The Bandoeng Conference of 1937: A milestone in health and development SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID PUBLIC-HEALTH C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA. [Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. [Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA. EM theodore_brown@urmc.rochester.edu NR 9 TC 4 Z9 4 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2008 VL 98 IS 1 BP 42 EP 43 DI 10.2105/AJPH.2007.119222 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 248TJ UT WOS:000252178200014 PM 18048776 ER PT J AU Hoppin, JA Umbach, DM London, SJ Henneberger, PK Kullman, GJ Alavanja, MCR Sandler, DP AF Hoppin, Jane A. Umbach, David M. London, Stephanie J. Henneberger, Paul K. Kullman, Greg J. Alavanja, Michael C. R. Sandler, Dale P. TI Pesticides and atopic and nonatopic asthma among farm women in the agricultural health study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE agricultural workers; allergy; asthma; organophosphates; pesticides ID AIRWAY HYPERREACTIVITY; RESPIRATORY SYMPTOMS; RISK-FACTORS; INSECTICIDE; APPLICATORS; EXPOSURE; WHEEZE; EXPRESSION; CHLORPYRIFOS; ACTIVATION AB Rationale: Risk factors for asthma among farm women are understudied. Objectives: We evaluated pesticide and other occupational exposures as risk factors for adult-onset asthma. Methods: Studying 25,814 farm women in the Agricultural Health Study, we used self-reported history of doctor-diagnosed asthma with or without eczema and/or hay fever to create two case groups: patients with atopic asthma and those with nonatopic asthma. We assessed disease-exposure associations with polytomous logistic regression. Measurements and Main Results: At enrollment (1993-1997), 702 women (2.7%) reported a doctor's diagnosis of asthma after age 19 years (282 atopic, 420 nonatopic). Growing upon a farm (61% of all farm women) was protective for atopic asthma (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.43-0.70) and, to a lesser extent, for nonatopic asthma (OR, 0.83; 95%CI, 0.68-1.02; P value for difference = 0.008). Pesticide use was almost exclusively associated with atopic asthma. Any use of pesticides on the farm was associated only with atopic asthma (OR, 1.46; 95% CI, 1.14-1.87). This association with pesticides was strongest among women who had grown up on a farm. Women who grew up on farms and did not apply pesticides had the lowest overall risk of atopic asthma (OR, 0.41; 95% CI, 0.27-0.62) compared with women who neither grew upon farms nor applied pesticides. A total of 7 of 16 insecticides, 2 of 11 herbicides, and 1 of 4 fungicides were significantly associated with atopic asthma; only permethrin use on crops was associated with nonatopic asthma. Conclusions: These findings suggest that pesticides may contribute to atopic asthma, but not nonatopic asthma, among farm women. C1 [Hoppin, Jane A.; London, Stephanie J.; Sandler, Dale P.] NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. [Umbach, David M.] NIEHS, NIH, Dept Hlth & Human Serv, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Henneberger, Paul K.; Kullman, Greg J.] NIOSH, Ctr Dis Control & Prevent, Dept Hlth & Human Serv, Div Resp Dis Studies, Morgantown, WV USA. [Alavanja, Michael C. R.] NCI, NIH, Dept Hlth & Human Serv, Occupat Epidemiol Branch, Rockville, MD USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018; London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS NR 39 TC 59 Z9 60 U1 2 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 1 PY 2008 VL 177 IS 1 BP 11 EP 18 DI 10.1164/rccm.200706-821OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 246BN UT WOS:000251982600004 PM 17932376 ER PT J AU Gitlow, S Willenbring, ML AF Gitlow, Stuart Willenbring, Mark L. TI Are medications that reduce risk of drinking or heavy drinking, or that promote abstinence, of value in the treatment of alcohol dependence? SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; METAANALYSIS; TOPIRAMATE C1 [Gitlow, Stuart] Mt Sinai Sch Med, Annenberg Phys Training Program Addict Dis, New York, NY 10029 USA. [Willenbring, Mark L.] NIAAA, Bethesda, MD USA. RP Gitlow, S (reprint author), Mt Sinai Sch Med, Annenberg Phys Training Program Addict Dis, 1212 5th Ave,15CDE, New York, NY 10029 USA. EM drgitlow@aol.com; mlw@niaaa.nin.gov NR 9 TC 0 Z9 0 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2008 VL 17 IS 1 BP 1 EP 4 DI 10.1080/10550490701756047 PG 4 WC Substance Abuse SC Substance Abuse GA 254JP UT WOS:000252583200001 PM 18214717 ER PT J AU Wu, LT Blazer, DG Stitzer, ML Patkar, AA Blaine, JD AF Wu, Li-Tzy Blazer, Dan G. Stitzer, Maxine L. Patkar, Ashwin A. Blaine, Jack D. TI Infrequent illicit methadone use among stimulant-using patients in methadone maintenance treatment programs: A National Drug Abuse Treatment Clinical Trials Network study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID UNITED-STATES; MEDICAL-TREATMENT; DETOXIFICATION; INCENTIVES; PREVALENCE; ADDICTION; AUSTRALIA; INJECTION; DIVERSION; DEATHS AB We sought to determine the prevalence, patterns, and correlates of past-month illicit methadone use and history of regular illicit use among stimulant-using methadone maintenance treatment patients. We obtained self-reported information on illicit methadone use from 383 participants recruited from six community-based methadone maintenance programs. Overall, 1.6% of participants reported illicit use in the past month, and 4.7% reported a history of regular use. Younger age and history of outpatient psychological treatment were associated with increased odds of past-month illicit use. Illicit methadone use among patients in maintenance programs is infrequent; however, a number of factors may increase risk of illicit use. C1 [Wu, Li-Tzy; Blazer, Dan G.; Patkar, Ashwin A.] Duke Univ, Sch Med, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Stitzer, Maxine L.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Blaine, Jack D.] Natl Inst Drug Abuse, Ctr Clin Trials network, Bethesda, MD USA. RP Wu, LT (reprint author), Duke Univ, Sch Med, Med Ctr, Dept Psychiat & Behav Sci, 2218-B Elder St,DUMC Box 3419, Durham, NC 27710 USA. EM litzy.wu@duke.edu FU NIDA NIH HHS [HHSN271200522071C]; PHS HHS [HHSN271200522071C] NR 37 TC 8 Z9 8 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2008 VL 17 IS 4 BP 304 EP 311 DI 10.1080/10550490802138913 PG 8 WC Substance Abuse SC Substance Abuse GA 323TJ UT WOS:000257471000008 PM 18612886 ER PT J AU Hardie, TL Moss, HB Lynch, KG AF Hardie, Thomas L. Moss, Howard B. Lynch, Kevin Gerard TI Sex differences in the heritability of alcohol problems SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ENVIRONMENTAL INFLUENCE; DEPENDENT INDIVIDUALS; GENDER-DIFFERENCES; UNITED-STATES; POPULATION; ABUSE; TWIN; HETEROGENEITY; INHERITANCE; INDICATORS AB Genetic factors may have a role in defining more coherent clinical phenotypes and subtypes in the DSM-V. Research has demonstrated that there are gender differences in the patterns of alcohol consumption, specific symptom endorsement, withdrawal effects, and rates of alcohol use disorders (AUD). We examined the sex-specific heritability of diagnostic symptoms for alcohol-related problems in a community-based sample of twin pairs (males: n = 519; females: n = 613) using a biometrical analytic strategy to estimate the genetic and environmental components of AUD symptoms. Five of the seven symptoms of alcohol problems demonstrated sex-differences in heritability. Three of the seven symptoms examined had significant heritability in female twins only: increased risk of injury or harm, emotional problems related to drinking, and the desire to drink. In males, a different pattern was observed, with four of the seven examined symptoms demonstrating heritability: Increased chance of injury or harm, spending more time using alcohol or getting over its effects, using larger amounts for longer periods of time than intended, and the need to use more alcohol to get the same effect. These data suggest that alcohol problems in females and males may be etiologically distinct, and that diagnostic criteria and therapeutics might be enhanced if these sex differences were taken into consideration. C1 [Hardie, Thomas L.] Univ Delaware, Dept Nursing, Newark, DE 19716 USA. [Moss, Howard B.] NIAAA, Rockville, MD 20852 USA. [Lynch, Kevin Gerard] Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. RP Hardie, TL (reprint author), Univ Delaware, Dept Nursing, Rm 315 McDowell Hall, Newark, DE 19716 USA. EM Thardie@udel.edu RI Hardie, Thomas/J-7776-2012; OI Hardie, Thomas/0000-0002-4547-7991 FU PHS HHS [P2ORR016472-08] NR 29 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2008 VL 17 IS 4 BP 319 EP 327 DI 10.1080/10550490802139010 PG 9 WC Substance Abuse SC Substance Abuse GA 323TJ UT WOS:000257471000010 PM 18612888 ER PT J AU Lloyd, JJ Strathdee, SA Pu, M Havens, JR Cornelius, LJ Huettner, S Latkin, CA AF Lloyd, Jacqueline J. Strathdee, Steffanie A. Pu, Minya Havens, Jennifer R. Cornelius, Llewellyn J. Huettner, Steven Latkin, Carl A. TI The impact of opiate agonist maintenance therapy on drug use within social networks of injecting drug users SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the College-of-Problems-on-Drug-Dependence CY JUN 19, 2007 CL Quebec City, CANADA SP Coll Problems Drug Dependence ID HIV RISK BEHAVIORS; OUT-OF-TREATMENT; IMMUNODEFICIENCY-VIRUS SEROCONVERSION; METHADONE-MAINTENANCE; PERSONAL NETWORKS; CASE-MANAGEMENT; ALCOHOL-USE; SUPPORT; ADDICTION; PARTNERS AB This study examined whether participation in opiate drug treatment is associated with changes in drug use and injecting drug use within the social networks of injecting drug users. Participants were 245 injecting drug users who attended the Baltimore Needle Exchange Program during 2002-2004 and requested treatment and received a referral for opiate agonist treatment as part of an intervention to improve treatment outcomes. Data included interviews at baseline, 3, 6, 12, and 18 months and drug treatment program agency records. The mean age of participants was 42.2 years; 77% were African American, 69% were male, and 48% entered treatment. Final generalized estimating equations (GEE) models indicated that participants that entered opiate drug treatment exhibited approximately a 20% decrease in the proportional odds of having friends that used drugs (p = 0.04). Additionally, participants that entered opiate drug treatment exhibited a 26% decrease in the proportional odds of having friends that injected drugs (p = 0.01). These findings contribute evidence to further understand the dynamics between opiate drug treatment, changes in social network risk, and treatment outcomes, as well as suggest an important role for peer-based interventions to support entry and retention in opiate drug treatment. C1 [Lloyd, Jacqueline J.] Temple Univ, Sch Social Adm, Philadelphia, PA 19122 USA. [Strathdee, Steffanie A.; Huettner, Steven; Latkin, Carl A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Strathdee, Steffanie A.; Pu, Minya] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Havens, Jennifer R.] Univ Kentucky, Coll Med, Lexington, KY USA. [Cornelius, Llewellyn J.] Univ Maryland, Sch Social Work, Baltimore, MD 21201 USA. RP Lloyd, JJ (reprint author), Natl Inst Drug Abuse, NIH, 6001 Execut Blud Room 5166 MSC 9589, Bethesda, MD 20892 USA. EM lloydj2@nida.nih.gov RI Strathdee, Steffanie/B-9042-2009; OI Havens, Jennifer/0000-0002-1753-7280 FU NIDA NIH HHS [DA09225] NR 46 TC 4 Z9 4 U1 3 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2008 VL 17 IS 5 BP 414 EP 421 DI 10.1080/10550490802268165 PG 8 WC Substance Abuse SC Substance Abuse GA 344AC UT WOS:000258896600010 PM 18770085 ER PT J AU Gruschus, JM AF Gruschus, James M. TI Do amyloid oligomers act as traps for misfolded proteins? A hypothesis SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article DE Misfolding diseases; soluble amyloid; prion; oligomer; complex; neurotoxicity; cytotoxicity; protein degradation; catalytic mechanism; beta sheet; therapies ID ALZHEIMERS-DISEASE; ENDOPLASMIC-RETICULUM; NEURODEGENERATIVE DISEASES; MOLECULAR CHAPERONES; CHANNEL HYPOTHESIS; QUALITY CONTROL; BETA-PEPTIDES; PRION PROTEIN; A-BETA; AGGREGATION AB Mounting evidence points to soluble peptide oligomers as the primary agents in various amyloid and prion diseases. Multiple mechanisms appear to contribute to the cytotoxic effects of these oligomers. Here, an additional, general mechanism is proposed - that soluble amyloid peptide oligomers serve as "all-purpose" beta strands that can interact with transiently unfolded or nascent proteins where interior beta-sheet edges are exposed. The proteins, trapped in misfolded states through this interaction, become substrates for ubiquitination, targeting them for proteasomal degradation. The increased load of ubiquitinated proteins could contribute to the impairment of the ubiquitin/proteasome system (UPS) seen in many amyloid-related diseases. This "misfolding trap" mechanism could be especially stressful in the endoplasmic reticulum, where the amyloid oligomers would compete with chaperones for nascent beta-sheet proteins. If the bound amyloid oligomer dissociates at some point after the misfolded protein is committed to the UPS pathway, the oligomer could then repeat the process, adding a catalytic aspect to the misfolding mechanism. Direct proof of this proposed mechanism requires detection of amyloid oligomer-beta-sheet protein complexes, and a co-immunoprecipitation experiment is proposed. This hypothesis supports therapies that increase amyloid oligomer degradation or sequestration, as well as therapies that upregulate chaperone activity, for combating amyloid-related diseases. C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Gruschus, JM (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 50,Rm 2343, Bethesda, MD 20892 USA. EM gruschus@helix.nih.gov FU National Heart, Lung & Blood Institute of the National Institutes of Health FX The author thanks P. Boon Chock, Ann Ginsburg, Lois E. Greene, and Evan Eisenberg for their helpful suggestions. This work was supported intramurally by the National Heart, Lung & Blood Institute of the National Institutes of Health NR 56 TC 10 Z9 10 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PY 2008 VL 15 IS 3 BP 160 EP 165 DI 10.1080/13506120802193746 PG 6 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 361IQ UT WOS:000260121700002 PM 18925454 ER PT J AU Cardoso, CL de Moraes, MC Guido, RVC Oliva, G Andricopulo, AD Wainer, IW Cass, QB AF Cardoso, Carmen Lucia de Moraes, Marcela Cristina Guido, Rafael Victorio Carvalho Oliva, Glaucius Andricopulo, Adriano Defini Wainer, Irving William Cass, Quezia Bezerra TI The development of an immobilized enzyme reactor containing glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi: the effect of species' specific differences on the immobilization SO ANALYST LA English DT Article ID CHAGAS-DISEASE; CHEMOTHERAPY; GLYCOLYSIS; CAPILLARY AB Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in the life cycle of the Trypanosoma cruzi, and an immobilized enzyme reactor (IMER) has been developed for use in the on-line screening for GAPDH inhibitors. An IMER containing human GAPDH has been previously reported; however, these conditions produced a T. cruzi GAPDH-IMER with poor activity and stability. The factors affecting the stability of the human and T. cruzi GAPDHs in the immobilization process and the influence of pH and buffer type on the stability and activity of the IMERs have been investigated. The resulting T. cruzi GAPDH-IMER was coupled to an analytical octyl column, which was used to achieve chromatographic separation of NAD+ from NADH. The production of NADH stimulated by D-glyceraldehyde-3-phosphate was used to investigate the activity and kinetic parameters of the immobilized T. cruzi GAPDH. The Michaelis-Menten constant (K-m) values determined for D-glyceraldehyde-3-phosphate and NAD(+) were K-m = 0.5 +/- 0.05 mM and 0.648 +/- 0.08 mM, respectively, which were consistent with the values obtained using the non-immobilized enzyme. C1 [de Moraes, Marcela Cristina; Cass, Quezia Bezerra] Univ Fed Sao Carlos, Dept Quim, BR-13565905 Sao Paulo, Brazil. [Cardoso, Carmen Lucia] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Pret, BR-14040901 Sao Paulo, Brazil. [Guido, Rafael Victorio Carvalho; Oliva, Glaucius; Andricopulo, Adriano Defini] Univ Sao Paulo, Inst Fis, Ctr Biotechnol Mol Estrut CBME, BR-14040901 Sao Paulo, Brazil. [Wainer, Irving William] Natl Inst Hlth, NIA, Baltimore, MD USA. RP Cass, QB (reprint author), Univ Fed Sao Carlos, Dept Quim, Cx Postal 676, BR-13565905 Sao Paulo, Brazil. EM quezia@dq.ufscar.br RI Guido, Rafael/A-7450-2009; Andricopulo, Adriano/B-7672-2012; Cass, Quezia/B-8188-2012; Oliva, Glaucius/B-9059-2012; 4, INCT/H-4499-2013; Inbeqmedi, Inct/I-1929-2013; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; Cardoso, Carmen Lucia/C-4422-2012; OI Guido, Rafael/0000-0002-7187-0818; Cass, Quezia/0000-0002-6550-1194; Cardoso, Carmen Lucia/0000-0001-6239-6651; de Moraes, Marcela/0000-0001-7448-5301 NR 14 TC 22 Z9 23 U1 1 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2008 VL 133 IS 1 BP 93 EP 99 DI 10.1039/b711145b PG 7 WC Chemistry, Analytical SC Chemistry GA 241VQ UT WOS:000251684300021 PM 18087619 ER PT J AU Moaddel, R Oliveira, RV Kimura, T Hyppolite, P Juhaszova, M Xiao, YX Kellar, KJ Bernier, M Wainer, IW AF Moaddel, Ruin Oliveira, Regina V. Kimura, Tomoko Hyppolite, Patrick Juhaszova, Magdalena Xiao, Yingxian Kellar, Kenneth J. Bernier, Michel Wainer, Irving W. TI Initial synthesis and characterization of an alpha 7 nicotinic receptor cellular membrane affinity chromatography column: Effect of receptor subtype and cell type SO ANALYTICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; ACETYLCHOLINE-RECEPTORS; STATIONARY PHASES; LIPID RAFTS; CONFORMATIONAL MOBILITY; ALPHA-3-BETA-4; PHARMACOLOGY; EPIBATIDINE; AGONIST AB In this study, cellular membrane fragments from SH-EP1-pCEP4-h alpha 7 and alpha 7 HEK-293 cell lines were used to synthesize cellular membrane affinity chromatography (CMAC) columns containing functional alpha 7 nicotinic acetylcholine receptors, CMAC(alpha 7 nAChR) columns. The synthesis of stable columns required the addition of cholesterol to the 2% cholate solubilization/immobilization (s/i) buffer and to the mobile phase. In addition, when membranes from the SH-EP1 cell line were used, L-alpha-phosphatidylserine and L-alpha-phosphatidylethanolamine also had to be added to the s/i buffer. A CMAC(alpha 4 beta 2 nAChR) column was prepared using membrane fragments from a SH-EP1-pCEP4-h alpha 4 beta 2 cell line, and this process required the addition of L-alpha-phosphatidylserine and L-alpha-hosphatidylethanolamine to the s/i buffer, but not cholesterol. The s/i buffers from the three columns were compared with the s/i buffer utilized in the preparation of a CMAC(alpha 4 beta 2 nAChR) column prepared using an alpha 4 beta 2 HEK-293 cell line, which required no additions to the 2% cholate s/i buffer. The data demonstrate that both cell type and receptor type affect the protocol required to produce a stable CMAC column and that, at the current time, the development of an optimum immobilization protocol is an empirical process. The results are also consistent with the observation that the alpha 7 nAChR is localized in lipid rafts in both of these cell fines and that the cholate detergent removed cholesterol from these microdomains. C1 [Moaddel, Ruin; Oliveira, Regina V.; Kimura, Tomoko; Hyppolite, Patrick; Juhaszova, Magdalena; Bernier, Michel; Wainer, Irving W.] NIA, Gerontol Res Ctr, Natl Inst Hlth, Baltimore, MD 21224 USA. [Xiao, Yingxian; Kellar, Kenneth J.] Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20057 USA. RP Moaddel, R (reprint author), NIA, Gerontol Res Ctr, Natl Inst Hlth, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov RI Oliveira, Regina/I-9547-2012; OI Bernier, Michel/0000-0002-5948-368X FU Intramural NIH HHS [Z99 AG999999, ZIA AG000295-13] NR 31 TC 20 Z9 20 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 1 PY 2008 VL 80 IS 1 BP 48 EP 54 DI 10.1021/ac701943b PG 7 WC Chemistry, Analytical SC Chemistry GA 246SH UT WOS:000252026900014 PM 18062706 ER PT J AU Kacinko, SL Shakleya, DM Huestis, MA AF Kacinko, Sherri L. Shakleya, Diaa M. Huestis, Marilyn A. TI Validation and application of a method for the determination of buprenorphine, norbuprenorphine, and their glucuronide conjugates in human meconium SO ANALYTICAL CHEMISTRY LA English DT Article ID CHROMATOGRAPHY-MASS SPECTROMETRY; GAS-CHROMATOGRAPHY; HUMAN-PLASMA; WITHDRAWAL SYNDROME; ENZYME-IMMUNOASSAY; HUMAN-URINE; PREGNANCY; METHADONE; ASSAY; HAIR AB A novel liquid chromatography tandem mass spectrometry method for quantification of buprenorphine, norbuprenorphine, and glucuronidated conjugates was developed and validated. Analytes were extracted from meconium using buffer, concentrated by solid-phase extraction and quantified within 13.5 min. In order to determine free and total concentrations, specimens were analyzed with and without enzyme hydrolysis. Calibration was achieved by linear regression with a 1/x weighting factor and deuterated internal standards. All analytes were linear from 20 to 2000 ng/g with a correlation of determination of > 0.98. Accuracy was >= 85.7% with intra-assay and interassay imprecision <= 13.9 and 12.4%, respectively. There was no interference from 70 licit and illicit drugs and metabolites. Buffer extraction followed by SPE yielded recoveries of >= 85.0%. There was suppression of ionization by the polar matrix; however, this did not interfere with sensitivity or analyte quantification due to inclusion of deuterated internal standards. Analytes were stable on the autosampler, at room temperature, at 4 degrees C, and when exposed to three freeze/thaw cycles. This sensitive and specific method can be used to monitor in utero buprenorphine exposure and to evaluate correlations, if any, between buprenorphine exposure and neonatal outcomes. C1 [Kacinko, Sherri L.; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Chem & Drug Metab Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Chem & Drug Metab Sect, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000412-10, Z01 DA000433-08, Z01 DA000414-10] NR 52 TC 18 Z9 18 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 1 PY 2008 VL 80 IS 1 BP 246 EP 252 DI 10.1021/ac701627q PG 7 WC Chemistry, Analytical SC Chemistry GA 246SH UT WOS:000252026900038 PM 18044957 ER PT J AU Gordon, SM Chuang, BP Wang, XM Hamza, MA Rowan, JS Brahim, JS Dionne, RA AF Gordon, Sharon M. Chuang, Brian P. Wang, Xiao Min Hamza, May A. Rowan, Janet S. Brahim, Jaime S. Dionne, Raymond A. TI The differential effects of bupivacaine and lidocaine on prostaglandin E-2 release, cyclooxygenase gene expression and pain in a clinical pain model SO ANESTHESIA AND ANALGESIA LA English DT Article ID INDUCED INFLAMMATORY RESPONSE; PERIPHERAL PROSTANOID LEVELS; CENTRAL-NERVOUS-SYSTEM; DORSAL-ROOT GANGLIA; POSTOPERATIVE PAIN; SPINAL-CORD; LOCAL-ANESTHETICS; CEREBROSPINAL-FLUID; UP-REGULATION; CENTRAL SENSITIZATION AB BACKGROUND: In addition to blocking nociceptive input from surgical sites, long-acting local anesthetics might directly modulate inflammation, In the present study, we describe the proinflammatory effects of bupivacaine on local prostaglandin E-2 (PGE(2,)) production and cyclooxygenase (COX) gene expression that increases postoperative pain in human subjects. METHODS: Subjects (n = 114) undergoing extraction of impacted third molars received either 2% lidocaine or 0.5% bupivacaine before surgery and either rofecoxib 50 mg or placebo orally 90 min before surgery and for the following 48 h. Oral mucosal biopsies were taken before surgery and 48 h after surgery. After extraction, a microdialysis probe was placed at the surgical site for PGE(2) and thromboxane B, (TXB2) measurements. RESULTS: The bupivacaine/rofecoxib group reported significantly less pain, as assessed by a visual analog scale, compared with the other three treatment groups over the first 4 h. However, the bupivacaine/placebo group reported significantly more pain at 24 h and PGE2 levels during the first 4 h were significantly higher than the other three treatment groups. Moreover, bupivacaine significantly increased COX-2 gene expression at 48 h as compared with the lidocaine/placebo group. Thromboxane levels were not significantly affected by any of the treatments, indicating that the effects seen were attributable to inhibition of COX-2, but not COX-1. CONCLUSIONS: These results suggest that bupivacaine stimulates COX-2 gene expression after tissue injury, which is associated with higher PGE(2) production and pain after the local anesthetic effect dissipates. C1 [Gordon, Sharon M.] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. [Wang, Xiao Min; Dionne, Raymond A.] NINR, Bethesda, MD 20892 USA. [Rowan, Janet S.] Clin Res Ctr, Dept Nursing, Bethesda, MD USA. [Brahim, Jaime S.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Hamza, May A.] Ain Shams Univ, Dept Pharmacol, Fac Med, Cairo, Egypt. RP Gordon, SM (reprint author), Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. EM SGordon@umaryland.edu RI Hamza, May/A-5053-2010 OI Hamza, May/0000-0002-7637-3060 FU Intramural NIH HHS NR 47 TC 19 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2008 VL 106 IS 1 BP 321 EP 327 DI 10.1213/01.ane.0000296474.79437.23 PG 7 WC Anesthesiology SC Anesthesiology GA 243VB UT WOS:000251824300056 PM 18165598 ER PT J AU Hampshire, VA Davis, JA AF Hampshire, Victoria A. Davis, Judith A. BE Fish, RE Brown, MJ Danneman, PJ Karas, AZ TI Postprocedural Care of Commonly Utilized Research Animal Subjects SO ANESTHESIA AND ANALGESIA IN LABORATORY ANIMALS, 2ND EDITION SE American College of Laboratory Animal Medicine Series LA English DT Article; Book Chapter ID ENVIRONMENTAL ENRICHMENT; LABORATORY-ANIMALS; HOUSING CONDITIONS; SKELETAL-MUSCLE; RODENT CARE; BEAGLE DOGS; MICE; BUPRENORPHINE; HYPOTHERMIA; NUTRITION C1 [Hampshire, Victoria A.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20855 USA. [Davis, Judith A.] NIAAA, Off Lab Anim Sci, DIR, NIH, Bethesda, MD 20892 USA. RP Hampshire, VA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20855 USA. NR 76 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 BN 978-0-12-373898-1 J9 AM COLL LAB PY 2008 BP 219 EP 235 PG 17 WC Veterinary Sciences SC Veterinary Sciences GA BED52 UT WOS:000316210000010 ER PT J AU Nicholson, A Klaunberg, B AF Nicholson, Anthony Klaunberg, Brenda BE Fish, RE Brown, MJ Danneman, PJ Karas, AZ TI Anesthetic Considerations for In Vivo Imaging Studies SO ANESTHESIA AND ANALGESIA IN LABORATORY ANIMALS, 2ND EDITION SE American College of Laboratory Animal Medicine Series LA English DT Article; Book Chapter ID RAY COMPUTED-TOMOGRAPHY; SMALL-ANIMAL PET; CARDIAC-FUNCTION; ECHOCARDIOGRAPHIC-ASSESSMENT; TRIBROMOETHANOL ANESTHESIA; ULTRASOUND BIOMICROSCOPY; ICR MICE; ENDOTRACHEAL INTUBATION; MECHANICAL VENTILATION; TRANSGENIC MICE C1 [Nicholson, Anthony] Jackson Lab, Bar Harbor, ME 04609 USA. [Klaunberg, Brenda] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. RP Nicholson, A (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. NR 90 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-373898-1 J9 AM COLL LAB PY 2008 BP 629 EP 639 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA BED52 UT WOS:000316210000031 ER PT J AU Barluenga, S Wang, CH Fontaine, JG Aouadi, K Beebe, K Tsutsumi, S Neckers, L Winssinger, N AF Barluenga, Sofia Wang, Cuihua Fontaine, Jean-Gonzague Aouadi, Kaiss Beebe, Kristin Tsutsumi, Shinji Neckers, Len Winssinger, Nicolas TI Divergent synthesis of a pochonin library targeting HSP90 and in vivo efficacy of an identified inhibitor SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE antitumor agents; bioorganic chemistry; natural products; solid-phase synthesis; synthesis design ID MOLECULAR CHAPERONE HSP90; BREAST-CANCER CELLS; BIOLOGICAL EVALUATION; ANTICANCER AGENT; ANTITUMOR-ACTIVITY; RADICICOL; GELDANAMYCIN; HEAT-SHOCK-PROTEIN-90; DERIVATIVES; ANALOGS C1 [Barluenga, Sofia; Wang, Cuihua; Fontaine, Jean-Gonzague; Aouadi, Kaiss; Winssinger, Nicolas] Univ Strasbourg 1, Inst Sci & Ingn Supramol, F-67000 Strasbourg, France. [Beebe, Kristin; Tsutsumi, Shinji; Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Winssinger, N (reprint author), Univ Strasbourg 1, Inst Sci & Ingn Supramol, 8 Allee Gaspard Monge, F-67000 Strasbourg, France. EM winssinger@isis.u-strasbg.fr RI Winssinger, Nicolas/B-6710-2017 OI Winssinger, Nicolas/0000-0003-1636-7766 FU Intramural NIH HHS [Z01 SC010074-12] NR 36 TC 38 Z9 38 U1 3 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2008 VL 47 IS 23 BP 4432 EP 4435 DI 10.1002/anie.200800233 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 308BX UT WOS:000256364400035 PM 18435518 ER PT J AU Uetrecht, C Versluis, C Watts, NR Wingfield, PT Steven, AC Heck, AJR AF Uetrecht, Charlotte Versluis, Cees Watts, Norman R. Wingfield, Paul T. Steven, Alasdair C. Heck, Albert J. R. TI Stability and shape of hepatitis B virus capsids in vacuo SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE analytical methods; conformational analysis ion mobility; mass spectrometry; viruses ID TANDEM MASS-SPECTROMETRY; ELECTRON CRYOMICROSCOPY; CONFORMATIONAL-CHANGES; PROTEIN COMPLEXES; CORE; INSTRUMENT; MICROSCOPY; BINDING; WATER C1 [Heck, Albert J. R.] Univ Utrecht, Biomol Mass Spectrometry & Prote Grp, Bijvoet Ctr Biomol Res, NL-3584 CA Utrecht, Netherlands. Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CA Utrecht, Netherlands. [Watts, Norman R.; Wingfield, Paul T.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. [Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Heck, AJR (reprint author), Univ Utrecht, Biomol Mass Spectrometry & Prote Grp, Bijvoet Ctr Biomol Res, Sorbonnelaan 16, NL-3584 CA Utrecht, Netherlands. EM a.j.r.heck@uu.nl RI Uetrecht, Charlotte/D-1883-2010; Heck, Albert/D-7098-2011 OI Uetrecht, Charlotte/0000-0002-1991-7922; Heck, Albert/0000-0002-2405-4404 FU Intramural NIH HHS [Z01 AR027002-29, Z01 AR041117-12] NR 37 TC 69 Z9 69 U1 0 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2008 VL 47 IS 33 BP 6247 EP 6251 DI 10.1002/anie.200802410 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 336HP UT WOS:000258355200025 PM 18642251 ER PT S AU McKinney, MC Weinstein, BM AF McKinney, Mary C. Weinstein, Brant M. BE Cheresh, DA TI USING THE ZEBRAFISH TO STUDY VESSEL FORMATION SO ANGIOGENESIS: IN VIVO SYSTEMS, PT A SE Methods in Enzymology LA English DT Review; Book Chapter ID EMBRYONIC VASCULAR DEVELOPMENT; ENDOTHELIAL-GROWTH-FACTOR; TRANSGENIC ZEBRAFISH; IN-VIVO; TRANSPARENT ZEBRAFISH; GENE-EXPRESSION; STEM-CELLS; WILD-TYPE; ANGIOGENESIS; MODEL AB Donio rerio, commonly referred to as the zebrafish, is a powerful animal model for studying the formation of the vasculature. Zebrafish offer unique opportunities for in vivo analysis of blood and lymphatic vessels formation because of their accessibility to large-scale genetic and experimental analysis as well as the small size, optical clarity, and external development of zebrafish embryos and larvae. A wide variety of established techniques are available to study vessel formation in the zebrafish, from early endothelial cell differentiation to adult vessel patterning. In this chapter, we review methods used to functionally manipulate and visualize the vasculature in the zebrafish and illustrate how these methods have helped further understanding of the genetic components regulating formation and patterning of developing vessels. C1 [McKinney, Mary C.; Weinstein, Brant M.] NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. RP McKinney, MC (reprint author), NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. FU National Institute of Child Health and Human Development FX This work was supported by the intramural prograrn of the National Institute of Child Health and Human Development. NR 111 TC 14 Z9 15 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 0076-6879 BN 978-0-12-374313-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 444 BP 65 EP 97 DI 10.1016/S0076-6879(08)02804-8 PG 33 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIM32 UT WOS:000260774700004 PM 19007661 ER PT J AU Kho, Y Kim, S Yoon, BS Moon, JH Kwak, S Park, G Woo, J Oh, S Hong, K Kim, S Kim, H You, S Choi, Y AF Kho, Yoonjung Kim, Sungchan Yoon, Byung Sun Moon, Jai-Hee Kwak, Sungwook Park, Gyuman Woo, Junghee Oh, Sejong Hong, Kichang Kim, Saehun Kim, Hyunggee You, Seungkwon Choi, Yunjaie TI WDNM1 is associated with differentiation and apoptosis of mammary epithelial cells SO ANIMAL BIOTECHNOLOGY LA English DT Article DE apoptosis; mammary epithelial cell; NF kappa B; TNF alpha; WDNM1 ID NF-KAPPA-B; REGULATORY FACTOR; IN-VIVO; ACTIVATION; DEATH; EXPRESSION; INVOLUTION; GENE; BINDING; ALPHA AB In this study, we show that expression of the Westmead DMBA8 nonmetastatic cDNA 1 (WDNM1) gene was increased upon SFM and/or TNF alpha treatment, with a corresponding increase in apoptotic cells, and gradually decreased following re-stimulation with serum in HC11 mammary epithelial cells. TNF alpha induced WDNM1 expression showed the NF kappa B-dependent mechanism since it's expression was abrogated in IBM (super-repressor of NF kappa B)-transfected cells, but not those transfected with control vector. Furthermore, overexpression of WDNM1 suppressed growth and differentiation, and accelerated apoptosis of HC11 cells. Thus, our results demonstrate that WDNM1 gene expression, regulated by the TNF alpha-NF kappa B signal pathway, is associated with HC11 cell apoptosis. C1 [Kho, Yoonjung; Kwak, Sungwook; Choi, Yunjaie] Seoul Natl Univ, Coll Agr & Life Sci, Sch Agr & Biotechnol, Seoul, South Korea. [Kim, Sungchan] Hallym Univ, Coll Med, Dept Biochem, Chunchon, South Korea. [Kho, Yoonjung; Kim, Sungchan; Yoon, Byung Sun; Moon, Jai-Hee; Park, Gyuman; Hong, Kichang; Kim, Saehun; Kim, Hyunggee; You, Seungkwon] Korea Univ, Coll Life Sci & Biotechnol, Lab Cell Growth & Funct Regulat, Seoul, South Korea. [Woo, Junghee] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. [Oh, Sejong] Chonnam Natl Univ, Coll Agr & Life Sci, Div Anim Sci, Kwangju, South Korea. RP Choi, Y (reprint author), Seoul Natl Univ, Coll Agr & Life Sci, Sch Agr & Biotechnol, Seoul, South Korea. EM bioseung@korea.ac.kr; cyjcow@snu.ac.kr RI Kim, Hyunggee/F-2673-2013; Kang, Phil Jun/F-4716-2013; Choi, Yunjaie /B-4697-2014; You, Seungkwon/H-3067-2015 OI Kim, Hyunggee/0000-0002-4738-0990; NR 44 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PY 2008 VL 19 IS 2 BP 89 EP 103 DI 10.1080/10495390801887361 PG 15 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 292NK UT WOS:000255273200004 PM 18432400 ER PT J AU Barrett, RE Cho, YI Weaver, KE Ryu, K Campbell, RT Dolecek, TA Warnecke, RB AF Barrett, Richard E. Cho, Young Ik Weaver, Kathryn E. Ryu, Kirak Campbell, Richard T. Dolecek, Therese A. Warnecke, Richard B. TI Neighborhood change and distant metastasis at diagnosis of breast cancer SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE breast cancer; distant metastasis; neighborhoods; stage at diagnosis; multilevel; health disparities; African Americans; whites; Hispanics; socioeconomic status ID SOCIOECONOMIC-STATUS; CAUTIONARY TALE; URBAN POVERTY; GALSTER,GEORGE,C. CONSEQUENCES; SOCIAL SUPPORT; REDISTRIBUTION; 1990S; RACE; SURVIVAL; STAGE AB PURPOSE: To test whether upward socioeconomic neighborhood change has an effect on probability of distant metastasis at diagnosis of breast cancer among women who live there. METHODS: Census tract data (N = 1,137) from Cook County. IL, from 1990 and 2000 and cancer registry data for female breast cancer cases for these census tracts from 1994-2000 (N = 21,516) were used. A multilevel model of 1990 baseline socioeconomic status (SES) of neighborhoods and degree of neighborhood change 1990-2000 (compositional characteristics) and patient's age and race/Hispanic status (individual characteristics) was constructed to predict distant metastasis (vs. local and regional stage) at diagnosis. RESULTS: While residence in a census tract with lower baseline SES in 1990 (higher concentrated disadvantage and immigration and lower concentrated affluence) and being African American were associated with increased odds of distant metastasis at diagnosis, residence in an improving census tract was also associated with increased odds of distant metastasis at diagnosis. CONCLUSIONS: Paradoxically, both measures of initial neighborhood disadvantage and upward neighborhood socioeconomic change were independently associated with greater odds of distant metastasis at diagnosis of breast cancer. Neighborhood social and economic change can affect health. C1 [Barrett, Richard E.; Ryu, Kirak] Univ Illinois, Dept Sociol, Chicago, IL 60608 USA. [Cho, Young Ik] Univ Illinois, Survey Res Lab, Chicago, IL 60608 USA. [Weaver, Kathryn E.; Campbell, Richard T.; Dolecek, Therese A.] Univ Illinois, Div Epidemiol & Biostat, Sch Publ Hlth, Chicago, IL 60608 USA. [Barrett, Richard E.; Cho, Young Ik; Weaver, Kathryn E.; Ryu, Kirak; Campbell, Richard T.; Dolecek, Therese A.; Warnecke, Richard B.] Univ Illinois, Program Canc Control & Populat Sci, Ctr Canc, Inst Hlth Res Policy, Chicago, IL 60608 USA. [Weaver, Kathryn E.] NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Barrett, RE (reprint author), Univ Illinois, Dept Sociol, Mail Code 312,1007 W Harrison St, Chicago, IL 60608 USA. EM barrett@uic.edu FU NCI NIH HHS [P50 CA106743, P-50 CA106743] NR 31 TC 23 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2008 VL 18 IS 1 BP 43 EP 47 DI 10.1016/j.annepidem.2007.07.001 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 246AN UT WOS:000251980000007 PM 17890103 ER PT J AU Brotman, RM Klebanoff, MA Nansel, T Zhang, J Schwebke, JR Yu, KF Zenilman, JM Andrews, WW AF Brotman, Rebecca M. Klebanoff, Mark A. Nansel, Tonja Zhang, Jun Schwebke, Jane R. Yu, Kai F. Zenilman, Jonathan M. Andrews, William W. TI Why do women douche? A longitudinal study with two analytic approaches SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE vaginal douching; vaginosis; bacterial ID PELVIC INFLAMMATORY DISEASE; CHLAMYDIA-TRACHOMATIS INFECTION; SEXUALLY-TRANSMITTED-DISEASES; BLACK-AND-WHITE; BACTERIAL VAGINOSIS; VAGINAL MICROFLORA; CASE-CROSSOVER; RISK-FACTORS; PREVALENCE; PREVENTION AB PURPOSE: Although vaginal douching is associated with several adverse outcomes, the reasons why women douche have not been studied prospectively. METHODS: Non-pregnant (N = 3620) women aged 15 to 44 years presenting for routine care at 12 clinics in Birmingham, Alabama, participated in a longitudinal study of vaginal flora (1999-2003). Participants were assessed quarterly for 1 year. The authors applied conditional logistic regression in a case-crossover analysis to determine the individual-level factors that vary between a woman's douching and non-douching intervals. Findings were compared to a population-level analysis utilizing generalized estimating equations. RESULTS: Thirty percent of participants douched in every interval; 28% douched in some but not all intervals. The case-crossover analysis indicated a woman was more likely to douche when reporting "fishy" vaginal odor (odds ratio [OR]:2.74; 95% confidence interval [Cl]: 1.55, 1.84), vaginal irritation (OR: 1.52; 95% Cl: 1.10, 2.11), summer month (OR: 1.37, 95% CI: 1.13, 1.67), or increase in number of sex partners (>= 3, OR: 2.42, 95% Cl: 1.11, 5.26). Bacterial vaginosis/trichomoniasis treatment (OR: 0.72, 95% CL: 0.59, 0.89) and absent menses (OR: 0.37, 95% Cl: 0.28, 0.50) were negatively associated with douching. These ORs were farther from the null than comparable population-level estimates. CONCLUSIONS: Programs targeting these predictors may decrease the untoward sequelae associated with douching. Furthermore, a case-crossover analysis applied to prospective studies can provide insights into time-varying factors. C1 [Zenilman, Jonathan M.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Brotman, Rebecca M.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Brotman, Rebecca M.; Klebanoff, Mark A.; Nansel, Tonja; Zhang, Jun; Yu, Kai F.] NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Rockville, MD USA. [Schwebke, Jane R.; Andrews, William W.] Univ Alabama, Birmingham, AL USA. RP Brotman, RM (reprint author), Johns Hopkins Bayview Med Ctr, Div Infect Dis, 4940 Eastern Ave,B-3 N, Baltimore, MD 21224 USA. EM rbrotman@jhsph.edu RI Brotman, Rebecca/H-5442-2011; OI Brotman, Rebecca/0000-0001-8762-6214; Nansel, Tonja/0000-0002-8298-7595 FU Intramural NIH HHS; NICHD NIH HHS [N0-1-HD-8-3293] NR 45 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2008 VL 18 IS 1 BP 65 EP 73 DI 10.1016/j.annepidem.2007.05.015 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 246AN UT WOS:000251980000010 PM 18063240 ER PT J AU Lampl, M Gotsch, F Kusanovic, JP Espinoza, J Goncalves, L Gomez, R Nien, JK Frongillo, EA Romero, R AF Lampl, Michelle Gotsch, Francesca Kusanovic, Juan Pedro Espinoza, Jimmy Goncalves, Luis Gomez, Ricardo Nien, Jyh Kae Frongillo, Edward A. Romero, Roberto TI Downward percentile crossing as an indicator of an adverse prenatal environment SO ANNALS OF HUMAN BIOLOGY LA English DT Article DE catch-down growth; fetal growth; preterm labor ID CATCH-UP GROWTH; NEONATAL OUTCOME WORSE; FETAL-GROWTH; GESTATIONAL-AGE; BIRTH-WEIGHT; INSULIN SENSITIVITY; PROSPECTIVE COHORT; SPIRAL ARTERIES; PRETERM LABOR; FACTOR-I AB Background: Postnatal health sequelae of low birth weight have been attributed to 'poor fetal growth' from inferred adverse prenatal environments; risks augmented by infant growth rates. Identifying prenatal growth-restricting events is essential to clarify pathways and mechanisms of fetal growth. Aim: The specific aim of this investigation was to examine whether an episode of preterm labor may compromise fetal growth. Subjects and methods: Fetal size at the end of the second trimester and birth were compared among women with uncomplicated pregnancies (n = 3167) and those who experienced an episode of preterm labor (<37 weeks) and subsequently delivered at term (>= 37 weeks, n = 147). Fetal weight estimated from ultrasound measures, and changes in weight standard scores across the third trimester investigated significant centile crossing (>0.67 standard deviation score change). Results: Fetuses delivered at term after an episode of preterm labor were smaller at birth relative to their peers than at the end of the second trimester, and were 47% more likely to experience clinically significant downward centile crossing (p < 0.05) than their peers (OR 1.47, 95% CI 1.04-2.07). Conclusion: An episode of preterm labor may signal an adverse prenatal environment for term-delivered neonates. Epidemiologically silent events in the natural history of pregnancy are an understudied source of fetal growth compromise as inferred by small birth size among peers. C1 [Lampl, Michelle] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. [Lampl, Michelle; Gotsch, Francesca; Kusanovic, Juan Pedro; Espinoza, Jimmy; Goncalves, Luis; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lampl, Michelle; Gotsch, Francesca; Kusanovic, Juan Pedro; Espinoza, Jimmy; Goncalves, Luis; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Kusanovic, Juan Pedro; Espinoza, Jimmy; Goncalves, Luis] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Gomez, Ricardo; Nien, Jyh Kae] Sotero Rio Hosp Puente Alto, Santiago, Chile. [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. RP Lampl, M (reprint author), Emory Univ, Dept Anthropol, 218C Geosci Bldg,1557 Dickey Dr, Atlanta, GA 30322 USA. EM mlampl@emory.edu RI Lampl, Michelle/B-1619-2013 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 43 TC 6 Z9 6 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0301-4460 J9 ANN HUM BIOL JI Ann. Hum. Biol. PY 2008 VL 35 IS 5 BP 462 EP 474 DI 10.1080/03014460802311062 PG 13 WC Anthropology; Biology; Public, Environmental & Occupational Health SC Anthropology; Life Sciences & Biomedicine - Other Topics; Public, Environmental & Occupational Health GA 354MS UT WOS:000259644300002 PM 18821324 ER PT J AU Roy-Gagnon, MH Mathias, RA Fallin, MD Jee, SH Broman, KW Wilson, AF AF Roy-Gagnon, M. -H. Mathias, R. A. Fallin, M. D. Jee, S. H. Broman, K. W. Wilson, A. F. TI An extension of the regression of offspring on mid-parent to test for association and estimate locus-specific heritability: The revised ROMP method SO ANNALS OF HUMAN GENETICS LA English DT Article DE association tests; quantitative trait; parent-offspring trios; candidate gene; cardiovascular disease ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; QUANTITATIVE TRAIT LOCI; FACTOR-VII LEVELS; CORONARY ARTERIOGRAPHY; LINKAGE DISEQUILIBRIUM; GENETIC-DETERMINANTS; HUMAN GENOME; FAMILIES; POLYMORPHISMS; INFORMATION AB The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMPrev) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus-specific heritability estimate. The ROMPrev test had good power at the 5% significance level with properly controlled type I error. Locus-specific heritability estimates were, on average, close to simulated values. For non-zero locus-specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest. ROMPrev was applied to a study of cardiovascular-related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMPrev method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus-specific heritability while minimizing the genotyping required. C1 [Roy-Gagnon, M. -H.; Mathias, R. A.; Wilson, A. F.] NHGRI, NIH, Genometr Sect, Inherited Dis Res Branch, Baltimore, MD 21224 USA. [Fallin, M. D.; Jee, S. H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Jee, S. H.] Yonsei Univ, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea. [Broman, K. W.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. RP Wilson, AF (reprint author), NHGRI, NIH, Genometr Sect, Inherited Dis Res Branch, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM afw@mail.nih.gov RI Wilson, Alexander/C-2320-2009; OI Broman, Karl/0000-0002-4914-6671 FU Intramural NIH HHS; NCRR NIH HHS [RR03655]; NHGRI NIH HHS [Z01-HG000200] NR 39 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2008 VL 72 BP 115 EP 125 DI 10.1111/j.1469-1809.2007.00401.x PN 1 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 247YT UT WOS:000252119200016 PM 18042270 ER PT J AU Hanson, RL Knowler, WC AF Hanson, R. L. Knowler, W. C. TI Design and analysis of genetic association studies to finely map a locus identified by linkage analysis: Assessment of the extent to which an association can account for the linkage SO ANNALS OF HUMAN GENETICS LA English DT Article DE conditional linkage analysis; genetic association; linkage disequilbrium ID QUANTITATIVE-TRAIT LOCI; LONGITUDINAL DATA-ANALYSIS; VARIANCE-COMPONENTS; PEDIGREE ANALYSIS; HASEMAN-ELSTON; MODELS; EXTENSIONS; GENOTYPE; SIGNAL AB Association studies are often used to finely map quantitative trait loci identified by linkage analysis. Once a polymorphism associated with the trait has been identified, it may be useful to conduct linkage analyses which adjust for this polymorphism to determine the extent to which the association accounts for the linkage signal. However, methods for conducting statistical significance tests for an observed reduction in the linkage signal are not well developed. In the present study we develop methods for assessment of the statistical significance of an observed reduction in the variance due to the linked locus, with variance components or with Haseman-Elston linkage methods. Simulations indicate that these methods have appropriate levels of type I error and that, like other association statistics, their power depends on the magnitude of linkage disequilibrium between functional and marker alleles and on the extent of similarity between the frequency of the functional allele and the frequency of the associated marker allele. These methods can help determine which association results are likely due to strong linkage disequilibrium with functional alleles and, thus, can facilitate the selection of small chromosomal regions for more extensive study. C1 [Hanson, R. L.; Knowler, W. C.] NIDDKD, Diabetes Epidemiol & Clin Res Sect, Phoenix, AZ 85014 USA. RP Hanson, RL (reprint author), NIDDKD, Diabetes Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rhanson@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS NR 38 TC 3 Z9 3 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2008 VL 72 BP 126 EP 139 DI 10.1111/j.1469-1809.2007.00382.x PN 1 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 247YT UT WOS:000252119200017 PM 17627801 ER PT J AU Tanskanen, M Peuralinna, T Polvikoski, T Notkola, IL Sulkava, R Hardy, J Singleton, A Kiuru-Enari, S Paetau, A Tienari, PJ Myllykangas, L AF Tanskanen, Maarit Peuralinna, Terhi Polvikoski, Tuomo Notkola, Irma-Leena Sulkava, Raimo Hardy, John Singleton, Andrew Kiuru-Enari, Sari Paetau, Anders Tienari, Pentti J. Myllykangas, Liisa TI Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study SO ANNALS OF MEDICINE LA English DT Article DE age; alpha2-macroglobulin; autopsy; gene; myocardial infarction; senile systemic amyloidosis; tau; transthyretin ID ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; ALPHA-2-MACROGLOBULIN; HAPLOTYPE; PROTEIN; BRAIN; ALPHA(2)-MACROGLOBULIN; POLYMORPHISM; DEPOSITION; DEMENTIA AB Background. Senile systemic amyloidosis (SSA) is characterized by deposition of wild-type transthyretin (TTR)-based amyloid in parenchymal organs in elderly individuals. Previously, no population-based studies have been performed on SSA. Methods. Here we have studied the prevalence and risk factors for SSA in a Finnish autopsied population aged 85 or over, as part of the population-based Vantaa 85+ Autopsy Study (n=256). The diagnosis of SSA was based on histological examination of myocardial samples stained with Congo red and anti-TTR immunohistochemistry. The genotype frequencies of 20 polymorphisms in 9 genes in subjects with and without SSA were compared. Results. The prevalence of SSA was 25%. SSA was associated with age, myocardial infarctions, the G/G (Val/Val) genotype of the exon 24 polymorphism in the alpha2-macroglobulin (alpha 2M), and the H2 haplotype of the tau gene (F-values 0.002, 0.004, 0.042, and 0.016). Conclusion. This population-based study shows that SSA is very common in old individuals, affecting one-quarter of people aged over 85 years. Myocardial infarctions and variation in the genes for alpha 2M and tau may be associated with SSA. C1 [Tanskanen, Maarit; Paetau, Anders] Univ Helsinki, Dept Pathol, FIN-00014 Helsinki, Finland. [Tanskanen, Maarit; Kiuru-Enari, Sari; Paetau, Anders; Tienari, Pentti J.] Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. [Peuralinna, Terhi; Kiuru-Enari, Sari; Tienari, Pentti J.] Biomedicum Helsinki, Neurosci Programme, Helsinki, Finland. [Polvikoski, Tuomo] Univ Newcastle, Inst Hlth & Aging, Newcastle Upon Tyne, Tyne & Wear, England. [Notkola, Irma-Leena] Finnish Informat Ctr Register Res, Helsinki, Finland. [Sulkava, Raimo] Univ Kuopio, Dept Publ Hlth, FIN-70211 Kuopio, Finland. [Sulkava, Raimo] Univ Kuopio, Gen Practice Div Geriatr, FIN-70211 Kuopio, Finland. [Sulkava, Raimo] Univ Kuopio, Cent Hosp, FIN-70211 Kuopio, Finland. [Hardy, John; Singleton, Andrew] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Helsinki, Dept Neurol, FIN-00014 Helsinki, Finland. [Myllykangas, Liisa] Univ Helsinki, Folkhalsan Inst Genet, FIN-00014 Helsinki, Finland. [Myllykangas, Liisa] Univ Helsinki, Ctr Neurosci, FIN-00014 Helsinki, Finland. RP Tanskanen, M (reprint author), Univ Helsinki, Dept Pathol, Haartmaninkatu 3,POB 21, FIN-00014 Helsinki, Finland. EM maarit.tanskanen@helsinki.fi RI Singleton, Andrew/C-3010-2009; Tienari, Pentti/A-4893-2012; Hardy, John/C-2451-2009 FU Medical Research Council [G0701075] NR 36 TC 73 Z9 74 U1 1 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2008 VL 40 IS 3 BP 232 EP 239 DI 10.1080/07853890701842988 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 289OP UT WOS:000255064100008 PM 18382889 ER PT J AU Rouse, D Hirtz, D Thom, E AF Rouse, D. Hirtz, D. Thom, E. TI Magnesium sulfate for the prevention of cerebral palsy: A randomized controlled trial SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 133rd Annual Meeting of the American-Neurological-Association CY SEP 21-24, 2008 CL Salt Lake City, UT SP Amer Neurol Assoc C1 NICHHD, Maternal Fetal Med Units Network, Birmingham, AL USA. NICHHD, Maternal Fetal Med Units Network, Bethesda, MD 20892 USA. NICHHD, Maternal Fetal Med Units Network, Rockville, MD USA. 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PY 2008 VL 64 SU 12 BP S81 EP S81 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 344JU UT WOS:000258923700275 ER PT J AU Shneider, NA Brown, M Smith, C Alvarez, FJ AF Shneider, Neil A. Brown, Meghan Smith, Courtney Alvarez, Francisco J. TI Gamma fusimotor neurons dependence on muscle spindle-derived GDNF SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 133rd Annual Meeting of the American-Neurological-Association CY SEP 21-24, 2008 CL Salt Lake City, UT SP Amer Neurol Assoc C1 [Brown, Meghan] NINDS, NIH, Bethesda, MD 20892 USA. [Shneider, Neil A.] Columbia Univ, Motor Neuron Ctr, New York, NY 10027 USA. [Smith, Courtney; Alvarez, Francisco J.] Wright State Univ, Dayton, OH 45435 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PY 2008 VL 64 SU 12 BP S70 EP S70 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 344JU UT WOS:000258923700272 ER PT J AU Burnett, BG Summer, CJ AF Burnett, Barrington G. Summer, Charlotte J. TI Targeting splicing in spinal muscular atrophy SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID PRE-MESSENGER-RNA; MYOCARDIAL-INFARCTION; EXCHANGE INHIBITOR; SINGLE NUCLEOTIDE; EXTRACELLULAR PH; TENASCIN-C; SMN2; GENE; REPERFUSION; CELLS C1 [Burnett, Barrington G.] NIH, Neurogenet Branch, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Summer, Charlotte J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Burnett, BG (reprint author), NIH, Neurogenet Branch, Natl Inst Neurol Disorders & Stroke, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2008 VL 63 IS 1 BP 3 EP 6 DI 10.1002/ana.21305 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 260KH UT WOS:000253008700002 PM 18232015 ER PT J AU Azad, N Annunziata, C Perroy, A Minasian, L Kotz, H Kohn, E AF Azad, N. Annunziata, C. Perroy, A. Minasian, L. Kotz, H. Kohn, E. TI Combinations anti-angiogenesis therapy with sorafenib and bevacizumab in advanced solid tumors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Azad, N.; Annunziata, C.; Perroy, A.; Minasian, L.; Kotz, H.; Kohn, E.] NCI, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 16 EP 16 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300004 ER PT J AU Khanna, C AF Khanna, C. TI Targeting the IGF-I pathway in pediatric sarcomas SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Khanna, C.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 17 EP 17 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300010 ER PT J AU Neckers, L AF Neckers, L. TI Biology of HSP90 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Neckers, L.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 17 EP 17 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300011 ER PT J AU Vonderhaar, B Meyer, M Fleming, J Ginsburg, E Bush, A Ali, M Lieber, S AF Vonderhaar, B. Meyer, M. Fleming, J. Ginsburg, E. Bush, A. Ali, M. Lieber, S. TI CD44+ enriches for cancer initiating cells while CD44+CD24+ and CD44+CD24- cells are equally tumorigenic in basal-like breast cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Vonderhaar, B.; Meyer, M.; Fleming, J.; Ginsburg, E.; Bush, A.; Ali, M.; Lieber, S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 19 EP 19 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300020 ER PT J AU Kummar, S Gutierrez, M Kinders, R Rubinstein, L Parchment, RE Phillips, L Ji, J Chen, A Homeffer, Y Juwara, L Yancey, M Murgo, AJ Collins, JM Tomaszewski, JE Doroshow, JH AF Kummar, S. Gutierrez, M. Kinders, R. Rubinstein, L. Parchment, R. E. Phillips, L. Ji, J. Chen, A. Homeffer, Y. Juwara, L. Yancey, M. Murgo, A. J. Collins, J. M. Tomaszewski, J. E. Doroshow, J. H. TI Phase 0 pharmacodynamic, pharmacokinetic study of ABT-888, an inhibitor of poly (ADP-ribose) polymerase (PARP), in patients with advanced malignancies SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Kummar, S.; Gutierrez, M.; Kinders, R.; Rubinstein, L.; Parchment, R. E.; Phillips, L.; Ji, J.; Chen, A.; Homeffer, Y.; Juwara, L.; Yancey, M.; Murgo, A. J.; Collins, J. M.; Tomaszewski, J. E.; Doroshow, J. H.] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 20 EP 20 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300024 ER PT J AU Dennis, PA AF Dennis, P. A. TI Overview of the PI3K/Akt/mTOR pathway SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Dennis, P. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 21 EP 21 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300029 ER PT J AU Rosenberg, S AF Rosenberg, S. TI Targeting cancer antigens using the adoptive transfer of genetically engineered lymphocytes SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Rosenberg, S.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 21 EP 21 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300028 ER PT J AU Bottaro, DP AF Bottaro, D. P. TI Antibody targeting of the HGF/c-Met pathway SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Bottaro, D. P.] NCI CCR, Bethesda, MD USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300035 ER PT J AU Linehan, WM Srinivasan, R Pinto, P Bratslavsky, G Merino, M Vocke, C Hong, SB Baba, M Bottaro, D Schmidt, L Neckers, L AF Linehan, W. M. Srinivasan, R. Pinto, P. Bratslavsky, G. Merino, M. Vocke, C. Hong, S. B. Baba, M. Bottaro, D. Schmidt, L. Neckers, L. TI Molecular targeting of kidney cancer gene pathways SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Linehan, W. M.; Srinivasan, R.; Pinto, P.; Bratslavsky, G.; Merino, M.; Vocke, C.; Hong, S. B.; Baba, M.; Bottaro, D.; Schmidt, L.; Neckers, L.] NCI, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010; Baba, Masaya/L-7490-2013 OI Bottaro, Donald/0000-0002-5057-5334; Baba, Masaya/0000-0002-5308-6683 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300037 ER PT J AU Melillo, G AF Melillo, G. TI Targeting hypoxia inducible factor 1 (HIF-1) for cancer therapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Melillo, G.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300039 ER PT J AU Wright, J Bates, S Piekarz, R AF Wright, John Bates, Susan Piekarz, Richard TI Clinical and mechanistic development of histone deacetylase (HDAC) inhibitors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Wright, John; Bates, Susan; Piekarz, Richard] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300040 ER PT J AU Fojo, A Yang, J Bates, SE Stein, W AF Fojo, A. Yang, J. Bates, S. E. Stein, W. TI Bevacizumab reduces the growth rate constants of renal carcinomas and its early discontinuation may have obviated a survival advantage SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Fojo, A.; Yang, J.; Bates, S. E.] NCI, Bethesda, MD 20892 USA. [Stein, W.] Hebrew Univ Jerusalem, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 24 EP 24 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300042 ER PT J AU Gulley, J AF Gulley, J. TI Phase I trial of a targeted therapy with a psa-based vaccine and ipilimumab in patients (pts) with metastatic castrate-resistant prostate cancer (CRPC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Gulley, J.] NCI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 24 EP 24 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300044 ER PT J AU Gutierrez, ME Kummar, S Gardner, ER Figg, W Chen, X Zajac-Kaye, M Yancey, MA Ivy, P Conley, B Melillo, G Giaccone, G Doroshow, JH Murgo, AJ AF Gutierrez, M. E. Kummar, S. Gardner, E. R. Figg, W. Chen, X. Zajac-Kaye, M. Yancey, M. A. Ivy, P. Conley, B. Melillo, G. Giaccone, G. Doroshow, J. H. Murgo, A. J. TI Phase I trial of 17-dimethylaminoethylamino-17demethoxygeldanamycin (17-DMAG) administered twice weekly SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Gutierrez, M. E.; Kummar, S.; Figg, W.; Chen, X.; Zajac-Kaye, M.; Yancey, M. A.; Ivy, P.; Giaccone, G.; Doroshow, J. H.; Murgo, A. J.] NIH, Rockville, MD USA. [Gardner, E. R.; Melillo, G.] SAIC Frederick Inc, Bethesda, MD USA. [Conley, B.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 24 EP 24 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300043 ER PT J AU Annunziata, CM Davis, RE Lam, LT Hurt, EM Shaffer, AL Staudt, LM AF Annunziata, C. M. Davis, R. E. Lam, L. T. Hurt, E. M. Shaffer, A. L. Staudt, L. M. TI The oncogene c-maf is upregulated by a MEK/ERK-dependent mechanism in multiple myeloma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Annunziata, C. M.; Davis, R. E.; Lam, L. T.; Hurt, E. M.; Shaffer, A. L.; Staudt, L. M.] NCI, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 25 EP 25 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300049 ER PT J AU Fojo, A Huang, H Menefee, M Edgerly, M Kotz, H Poruchynsky, M Stein, W Bates, SE AF Fojo, A. Huang, H. Menefee, M. Edgerly, M. Kotz, H. Poruchynsky, M. Stein, W. Bates, S. E. TI The targeted agent ixabepilone [ixempra; BMS-247550] avoids MDR-1/P-glycoprotein mediated transport and is active in metastatic renal cell carcinoma (MRCC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Fojo, A.; Huang, H.; Edgerly, M.; Kotz, H.; Poruchynsky, M.; Bates, S. E.] NCI, Bethesda, MD 20892 USA. [Menefee, M.] Mayo Clin, Jacksonville, FL 32224 USA. [Stein, W.] Hebrew Univ Jerusalem, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 25 EP 25 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300046 ER PT J AU Karakunnel, JJ Gulley, JL Arlen, P Mulquin, M Wright, J Turkbey, IB Choyke, P Ahlers, CM Figg, WD Dahut, W AF Karakunnel, J. J. Gulley, J. L. Arlen, P. Mulquin, M. Wright, J. Turkbey, I. B. Choyke, P. Ahlers, C. M. Figg, W. D. Dahut, W. TI Phase II trial of cediranib (AZD 2171) in docetaxel-resistant, castrate-resistant prostate cancer (CRPC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Karakunnel, J. J.; Gulley, J. L.; Arlen, P.; Mulquin, M.; Wright, J.; Turkbey, I. B.; Choyke, P.; Ahlers, C. M.; Figg, W. D.; Dahut, W.] NCI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 25 EP 25 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300045 ER PT J AU Lee, MJ Kim, YS Chung, EJ Lee, S Janik, JE Morris, JC Kajiguchi, T Pise-Masison, C O'Mahony, D Waldmann, TA Brady, JN Trepel, JB AF Lee, M-J. Kim, Y. S. Chung, E. J. Lee, S. Janik, J. E. Morris, J. C. Kajiguchi, T. Pise-Masison, C. O'Mahony, D. Waldmann, T. A. Brady, J. N. Trepel, J. B. TI Beta-catenin signaling regulates acute adult T-cell leukemia/lymphoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Lee, M-J.; Kim, Y. S.; Chung, E. J.; Lee, S.; Janik, J. E.; Morris, J. C.; Kajiguchi, T.; Pise-Masison, C.; O'Mahony, D.; Waldmann, T. A.; Brady, J. N.; Trepel, J. B.] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 25 EP 25 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300048 ER PT J AU ElMasri, WM Rasool, N Kohn, EC AF ElMasri, W. M. Rasool, N. Kohn, E. C. TI Upregulation of secretory leukocyte protease inhibitor in ovarian cancer cells is protective against paclitaxel SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [ElMasri, W. M.; Rasool, N.; Kohn, E. C.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300053 ER PT J AU Zhang, C Elkahloun, AG Messan, KS Dennis, PA AF Zhang, C. Elkahloun, A. G. Messan, K. S. Dennis, P. A. TI Rapid and selective transcriptional activation of the tumor suppressor RHOS by lipid-based Akt inhibitors through C/EBPBETA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Zhang, C.; Messan, K. S.; Dennis, P. A.] NCI, Bethesda, MD 20892 USA. [Elkahloun, A. G.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300052 ER PT J AU Basu, NK Basu, M Owens, IS AF Basu, N. K. Basu, M. Owens, I. S. TI Targeted inhibition of PKC-dependent phosphorylation of UDP-glucuronosyltransferases by curcumin markedly improves drug efficacy of highly glucuronidatable SN-38 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Basu, N. K.; Basu, M.; Owens, I. S.] NICHHD, Sect Genet Disorders Drug Metab, PDEGEN, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 27 EP 27 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300058 ER PT J AU Bates, SE To, KW Polgar, O Huff, LM Zhan, Z Luchenko, V Robey, RW Piekarz, R AF Bates, S. E. To, K. W. Polgar, O. Huff, L. M. Zhan, Z. Luchenko, V. Robey, R. W. Piekarz, R. TI Epigenetic regulation of the multidrug-resistance gene abcg2 by demethylating agents, histone deacetylase (HDAC) inhibitors, and micrornas SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Bates, S. E.; To, K. W.; Polgar, O.; Huff, L. M.; Zhan, Z.; Luchenko, V.; Robey, R. W.; Piekarz, R.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 27 EP 27 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300055 ER PT J AU Tandle, A Hanna, E Lorang, D Hajitou, A Moya, CA Pasqualini, R Arap, W Adem, A Starker, E O'Connor, S Keck, V Hewitt, S Libutti, SK AF Tandle, A. Hanna, E. Lorang, D. Hajitou, A. Moya, C. A. Pasqualini, R. Arap, W. Adem, A. Starker, E. O'Connor, S. Keck, V. Hewitt, S. Libutti, S. K. TI Targeted anti-vascular gene delivery to tumor vasculature SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Tandle, A.; Hanna, E.; Lorang, D.; Hajitou, A.; Moya, C. A.; Pasqualini, R.; Arap, W.; Adem, A.; Starker, E.; O'Connor, S.; Keck, V.; Hewitt, S.; Libutti, S. K.] NCI, Tumor Angiogenesis Sect, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 27 EP 27 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300057 ER PT J AU Robles, A Caldas-Lopes, E Chiosis, G Varticovski, L AF Robles, A. Caldas-Lopes, E. Chiosis, G. Varticovski, L. TI Synergy of the purine-scaffold hsp90 inhibitor, PU-H71, with doxorubicin and etoposide in non-hodgkin's lymphoma cell lines SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Robles, A.; Varticovski, L.] NCI, CCR, Bethesda, MD 20892 USA. [Caldas-Lopes, E.; Chiosis, G.] Sloan Kettering Inst Canc Res, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 30 EP 30 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300067 ER PT J AU Rajan, A Gutierrez, M Giaccone, G AF Rajan, A. Gutierrez, M. Giaccone, G. TI Newer opportunities in systemic therapy of lung cancer SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 33rd European-Society-for-Medical-Oncology Congress CY SEP 12-16, 2008 CL Stockholm, SWEDEN SP European Soc Med Oncol ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; HUMAN SMALL-CELL; GEFITINIB RESISTANCE; ACQUIRED-RESISTANCE; SIGNALING PATHWAYS; PHASE-II; IN-VIVO; ANGIOGENESIS; ERLOTINIB C1 [Rajan, A.; Gutierrez, M.; Giaccone, G.] NCI, Bethesda, MD 20892 USA. RP Rajan, A (reprint author), NCI, Bethesda, MD 20892 USA. RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 52 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 7 BP 31 EP 37 DI 10.1093/annonc/mdn445 PG 7 WC Oncology SC Oncology GA 354CH UT WOS:000259616000004 ER PT J AU Haluska, P Stensgard, BA Qin, R Felten, SJ Batzel, GN Ivy, SP Toft, DO Erlichman, C AF Haluska, P. Stensgard, B. A. Qin, R. Felten, S. J. Batzel, G. N. Ivy, S. P. Toft, D. O. Erlichman, C. TI Phase I study of 17-allylamino-17 demethoxygeldanamycin (17-AAG), gemcitabine (Gem) and/or cisplatin (CDDP) in solid tumor patients SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Haluska, P.; Stensgard, B. A.; Qin, R.; Felten, S. J.; Batzel, G. N.; Toft, D. O.; Erlichman, C.] Mayo Clin, Rochester, MN USA. [Ivy, S. P.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 34 EP 34 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300080 ER PT J AU Voortman, J Ceresa, C Giovannetti, E Laan, AC Honeywell, R Giaccone, G Peters, GJ AF Voortman, J. Ceresa, C. Giovannetti, E. Laan, A. C. Honeywell, R. Giaccone, G. Peters, G. J. TI Bortezomib induces schedule-dependent modulation of gemcitabine pharmacokinetics and pharmacodynamics in non-small cell lung cancer and peripheral blood mononuclear cells SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Voortman, J.; Giovannetti, E.; Laan, A. C.; Honeywell, R.; Peters, G. J.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Ceresa, C.] Univ Milano Bicocca, Monza, Italy. [Giaccone, G.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 34 EP 34 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300081 ER PT J AU Gutierrez, M Kummar, S Allen, D Turkbey, B Choyke, P Wright, J Kurkjian, C Melillo, G Giaccone, G Doroshow, J Murgo, AJ AF Gutierrez, M. Kummar, S. Allen, D. Turkbey, B. Choyke, P. Wright, J. Kurkjian, C. Melillo, G. Giaccone, G. Doroshow, J. Murgo, A. J. TI A phase II study of multikinase inhibitor sorafenib in patients with relapsed non-small cell lung cancer (NSCLC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Gutierrez, M.; Murgo, A. J.] NCI, NIH, Bethesda, MD 20892 USA. [Melillo, G.] SAIC Frederick Inc, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 36 EP 36 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300084 ER PT J AU Piekarz, R Gardner, E Zhan, Z Obrzut, T Steinberg, S Liewehr, D Figg, W Prince, M Allen, S Kirschbaum, M Zain, J Bates, SE AF Piekarz, R. Gardner, E. Zhan, Z. Obrzut, T. Steinberg, S. Liewehr, D. Figg, W. Prince, M. Allen, S. Kirschbaum, M. Zain, J. Bates, S. E. TI Pharmacokinetic and biomarker analysis in a phase II trial of the HDAC inhibitor romidepsin, FK228 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Piekarz, R.; Gardner, E.; Zhan, Z.; Obrzut, T.; Steinberg, S.; Liewehr, D.; Figg, W.; Bates, S. E.] NIH, Bethesda, MD 20892 USA. [Prince, M.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Allen, S.] N Shore Univ Hosp, Manhasset, NY USA. [Kirschbaum, M.; Zain, J.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 36 EP 37 PG 2 WC Oncology SC Oncology GA 318EL UT WOS:000257074300086 ER PT J AU Linguraru, MG Yao, J Gautam, R Peterson, J Linehan, WM Summers, RM AF Linguraru, M. G. Yao, J. Gautam, R. Peterson, J. Linehan, W. M. Summers, R. M. TI Clinical tool for kidney cancer quantification and classification SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Linguraru, M. G.; Yao, J.; Summers, R. M.] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Gautam, R.; Peterson, J.; Linehan, W. M.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 38 EP 38 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300092 ER PT J AU Sissung, TM Baum, CE Deeken, J Price, DK Steinberg, SM Dahut, W Sparreboom, A Figg, WD AF Sissung, T. M. Baum, C. E. Deeken, J. Price, D. K. Steinberg, S. M. Dahut, W. Sparreboom, A. Figg, W. D. TI ABCB1 genetic variation influences the toxicity and clinical outcome of patients treated with docetaxel SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Sissung, T. M.; Baum, C. E.; Deeken, J.; Price, D. K.; Steinberg, S. M.; Dahut, W.; Sparreboom, A.; Figg, W. D.] NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 39 EP 40 PG 2 WC Oncology SC Oncology GA 318EL UT WOS:000257074300096 ER PT J AU Gao, R Price, D Sissung, T Reed, E Figg, WD AF Gao, R. Price, D. Sissung, T. Reed, E. Figg, W. D. TI Ethnic disparities in Americans of European descent versus Americans of African descent related to polymorphic ERCC1, ERCC2, XRCC1 and PAPR1 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 6th International Symposium on Target Anticancer Therapies CY MAR 20-22, 2008 CL Bethesda, MD SP NDDO Res Fdn, ESMO, NCI, MDICT Task Force C1 [Gao, R.; Price, D.; Sissung, T.; Figg, W. D.] NCI, Bethesda, MD 20892 USA. [Reed, E.] Ctr Dis Control & Prevent, Atlanta, GA USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 3 BP 42 EP 42 PG 1 WC Oncology SC Oncology GA 318EL UT WOS:000257074300101 ER PT J AU Tan, AR Steinberg, SM Parr, AL Nguyen, D Yang, SX AF Tan, A. R. Steinberg, S. M. Parr, A. L. Nguyen, D. Yang, S. X. TI Markers in the epidermal growth factor receptor pathway and skin toxicity during erlotinib treatment SO ANNALS OF ONCOLOGY LA English DT Article DE EGFR pathway markers; erlotinib; skin toxicity ID TYROSINE KINASE INHIBITOR; METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; BREAST-CANCER; END-POINTS; DIFFERENTIATION; EXPRESSION; MANAGEMENT; OSI-774; TRIAL AB Background: Skin toxicity is a common adverse effect of erlotinib and other anti-epidermal growth factor receptor (EGFR) agents. The aim of the study was to explore the relationship between markers in the EGFR pathway and skin rash. Patients and methods: Eighteen patients with metastatic breast cancer were treated with daily oral erlotinib at 150 mg. Skin biopsies were obtained at baseline and after 1 month of treatment in 15 patients. EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated Akt (pAkt) or Ki67 were examined quantitatively by immunohistochemistry. Results: 11 of 18 (61%, 95% confidence interval 35.7% to 82.7%) patients developed skin rash. pAkt at baseline was significantly higher in patients with no rash than those with a grade 1 or 2 rash (18.8 +/- 8.3 versus 2.4 +/- 1.2 versus 3.3 +/- 3.3; P = 0.0017 for trend). There was a trend towards a significant increase of pMAPK in skin posttreatment with increasing grade of rash (no rash versus grade 1 versus grade 2 rash: 4.5 +/- 2.3 versus 8.4 +/- 4.2 versus 19.4 +/- 4.6; P = 0.036). Other markers were not associated with rash. Conclusions: pAkt was significantly associated with not developing a rash and may have a predictive utility for skin toxicity in patients treated with erlotinib and possibly with other anti-EGFR agents. C1 [Parr, A. L.; Nguyen, D.; Yang, S. X.] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Tan, A. R.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, S. M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yang, SX (reprint author), NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, 37 Convent Dr,Bldg 37,Room 1048A, Bethesda, MD 20892 USA. EM xy32m@nih.gov FU Intramural NIH HHS NR 18 TC 13 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2008 VL 19 IS 1 BP 185 EP 190 DI 10.1093/annonc/mdm444 PG 6 WC Oncology SC Oncology GA 262VP UT WOS:000253176400029 PM 17878175 ER PT J AU Stein, U Arlt, F Walther, W Smith, J Fichtner, I Herrmann, P Birchmeier, W Schlag, PM Shoemaker, RH AF Stein, U. Arlt, F. Walther, W. Smith, J. Fichtner, I. Herrmann, P. Birchmeier, W. Schlag, P. M. Shoemaker, R. H. TI S100A4, a newly identified target gene of beta-catenin/TCF signalling in colon cancer, is of diagnostic and prognostic relevance for metastasis SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT European Multidisciplinary Colorectal Cancer Congress CY FEB 24-26, 2008 CL Berlin, GERMANY C1 [Stein, U.; Arlt, F.; Walther, W.; Smith, J.; Fichtner, I.; Birchmeier, W.] Max Delbruck Ctr Mol Med, Berlin, Germany. [Herrmann, P.; Schlag, P. M.] Free Univ Berlin, Klinikum Rudolf Virchow, Robert Rossle Klin, D-13122 Berlin, Germany. [Shoemaker, R. H.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2008 VL 19 SU 1 BP I21 EP I21 PG 1 WC Oncology SC Oncology GA 283SY UT WOS:000254658000037 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, Chung-Jyi Leitzmann, Michael F. Willett, Walter C. Giovannucci, Edward L. TI Long-chain saturated fatty acids consumption and risk of gallstone disease among men SO ANNALS OF SURGERY LA English DT Article ID CHOLESTEROL-FED HAMSTERS; DIETARY-FAT; INSULIN SENSITIVITY; GALLBLADDER-DISEASE; METABOLIC SYNDROME; BILIARY LIPIDS; STEARIC-ACID; SERUM-LIPIDS; TERM INTAKE; RESISTANCE AB Background: Various saturated fatty acids have different effects on blood lipids and insulin secretion in experiments. The effect of long-term consumption of specific and different classes of saturated fatty acids on the risk of gallstone disease in humans is unknown. Methods: We prospectively studied consumption of saturated fatty acids and risk of gallstone disease in a cohort of 44,524 US men from 1986 to 2002. Intake of saturated fatty acids was assessed using a validated semiquantitative food frequency questionnaire. Newly diagnosed gallstone disease was ascertained biennially. Results: During 584,679 person-years of follow-up, we documented 2350 incident cases of gallstone disease, of which 1387 cases required cholecystectomy. Compared with men in the lowest quintile of dietary intake of long-chain saturated fats, after adjustment for age and other potential risk factors, the relative risk of gallstone disease for men in the highest quintile was 1.24 [95% confidence interval (CI), 1.02, 1.50, P for trend = 0.03], and the relative risk of cholecystectomy for men in the highest quintile was 1.41 (CI, 1.09, 1.82, P for trend = 0.008). Consumption of medium-chain saturated fatty acids or short-chain saturated fatty acids was unrelated to the risk. Conclusions: Our results suggest that a higher consumption of long-chain saturated fatty acids may enhance the risk of gallstone disease,in men. C1 [Tsai, Chung-Jyi] Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA. [Tsai, Chung-Jyi; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA. [Leitzmann, Michael F.] NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Bethesda, MD 20892 USA. RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA. EM hpcjt@channing.harvard.edu NR 57 TC 15 Z9 15 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2008 VL 247 IS 1 BP 95 EP 103 DI 10.1097/SLA.0b013e31815792c2 PG 9 WC Surgery SC Surgery GA 246BL UT WOS:000251982400015 PM 18156928 ER PT J AU Isenberg, JS Pappan, LK Romeo, MJ Abu-Asab, M Tsokos, M Wink, DA Frazier, WA Roberts, DD AF Isenberg, Jeff S. Pappan, Loretta K. Romeo, Martin J. Abu-Asab, Mones Tsokos, Maria Wink, David A. Frazier, William A. Roberts, David D. TI Blockade of thrombospondin-1-CD47 interactions prevents necrosis of full thickness skin grafts SO ANNALS OF SURGERY LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; MUSCLE-CELL RESPONSES; VASCULAR NITRIC-OXIDE; PHYSICAL-ACTIVITY; WOUND CLOSURE; GROWTH-FACTOR; L-ARGININE; SURVIVAL; ANGIOGENESIS; FLAPS AB Background: Skin graft survival and healing requires rapid restoration of blood flow to the avascular graft. Failure or delay in the process of graft vascularization is a significant source of morbidity and mortality. One of the primary regulators of blood flow and vessel growth is nitric oxide (NO). The secreted protein thrombospondin-1 (TSPI) limits NO-stimulated blood flow and growth and composite tissue survival to ischemia. We herein demonstrate a role for TSP 1 in regulating full thickness skin graft (FTSG) survival. Methods and Results: FTSG consistently fail in wild type C57BL/6 mice but survive in mice lacking TSP1 or its receptor CD47. Ablation of the TSPI receptor CD36, however, did not improve FTSG survival. Remarkably, wild type FTSG survived on TSP I null or CD47 null mice, indicating that TSP1 expression in the wound bed is the primary determinant of graft survival. FTSG survival in wild type mice could be moderately improved by increasing NO flux, but graft survival was increased significantly through antibody blocking of TSPI binding to CD47 or antisense morpholino oligonucleotide suppression of CD47. Conclusions: TSP1 through CD47 limits skin graft survival. Blocking TSP1 binding or suppressing CD47 expression drastically increases graft survival. The therapeutic applications of this approach could include burn patients and the broader group of people requiring grafts or tissue flaps for closure and reconstruction of complex wounds of diverse etiologies. C1 [Isenberg, Jeff S.; Romeo, Martin J.; Abu-Asab, Mones; Tsokos, Maria; Wink, David A.; Roberts, David D.] NCI, Pathol Lab, NIH, Radiat Biol Branch, Bethesda, MD 20892 USA. [Pappan, Loretta K.; Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO USA. RP Isenberg, JS (reprint author), NCI, Pathol Lab, NIH, Radiat Biol Branch, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM isenberj@mail.nih.gov RI Roberts, David/A-9699-2008; OI Roberts, David/0000-0002-2481-2981; Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z01 SC009172-04]; NHLBI NIH HHS [R56 HL054390, R01 HL054390, HL 54390]; NIGMS NIH HHS [GM 57573, R01 GM057573] NR 54 TC 47 Z9 47 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2008 VL 247 IS 1 BP 180 EP 190 DI 10.1097/SLA.0b013e31815685dc PG 11 WC Surgery SC Surgery GA 246BL UT WOS:000251982400026 PM 18156939 ER PT J AU Sternheim, A Jin, XL Shmookler, B Jelinek, J Malawer, MM AF Sternheim, Amir Jin, Xiaolong Shmookler, Barry Jelinek, James Malawer, Martin M. TI 'Telangiectatic' transformation in soft tissue sarcomas. A clinicopathology analysis of an aggressive feature of high-grade sarcomas SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE soft tissue sarcoma; tumor necrosis; hemorrhagic sarcoma ID CHEMOTHERAPY-INDUCED NECROSIS; PROGNOSTIC-FACTOR; NEOADJUVANT CHEMOTHERAPY; EWINGS-SARCOMA; OSTEOSARCOMA; EXTREMITIES; SURVIVAL; BONE AB Background: 'Telangiectatic' change, which contains a large fluid hemorrhagic component, occurs in a variety of high-grade soft tissue sarcomas. Methods: In a retrospective database review, we identified 20 consecutive patients (3%) with 'telangiectatic' change in soft tissue sarcomas. Results: Tumors were located in the thigh (55%), shoulder (15%), calf (15%), upper arm (10%), and buttock in one patient. All 20 tumors were high grade. Histological diagnoses were MFH (40%), leiomyosarcoma (15%), synovial sarcoma (10%), and one each of seven other sarcomas (35%). Tumor size was often large-more than 10 cm (35%), between 5 and 10 cm (60%), and less than 5 cm in one case. A history of contusion to the tumor site followed by swelling was recorded in 30% of patients and 80% presented with a painful mass. On MRI imaging, 60% of tumors appeared to contain more than 50% blood, 50% had a hemosiderin-laden rim, and 55% had well-defined tumor nodules within the wall of the hematoma. Limb-sparing surgery was carried out in 90% of patients, the other 10% underwent primary amputation. The 5-year, event-free survival rate was 30%. Of the patients, 15% presented initially with metastatic disease; in 53%, it developed within 2 years of diagnosis. The overall local recurrence rate was 30%. Conclusions: Telangiectatic transformation in soft tissue sarcomas is a rare feature of aggressive high-grade soft tissue sarcomas and is unique in its clinical presentation, MRI characteristics, pathological pattern, and a tendency for a worse-off prognosis. C1 [Sternheim, Amir; Malawer, Martin M.] Washington Hosp Ctr, Washington Canc Inst, Dept Orthoped Oncol, Washington, DC 20010 USA. [Jin, Xiaolong; Shmookler, Barry] Washington Hosp Ctr, Washington Canc Inst, Dept Pathol, Washington, DC 20010 USA. [Jelinek, James] Washington Hosp Ctr, Washington Canc Inst, Dept Radiol, Washington, DC 20010 USA. [Malawer, Martin M.] Georgetown Univ, Washington, DC USA. [Malawer, Martin M.] NCI, Pediat & Surg Branch, Bethesda, MD 20892 USA. RP Sternheim, A (reprint author), Washington Hosp Ctr, Washington Canc Inst, Dept Orthoped Oncol, Washington, DC 20010 USA. EM amirsternheim@gmail.com NR 19 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2008 VL 15 IS 1 BP 345 EP 354 DI 10.1245/s10434-007-9637-8 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 249TD UT WOS:000252251800050 PM 17940825 ER PT S AU Tian, P AF Tian, Pu BE Webb, GA TI Molecular dynamics simulations of nanoparticles SO ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY 2008, VOL 104, SECTION C: PHYSICAL CHEMISTRY SE Annual Reports on the Progress of Chemistry Section C-Physical Chemistry LA English DT Review; Book Chapter ID DISSIPATIVE PARTICLE DYNAMICS; RADIAL-DISTRIBUTION FUNCTIONS; COMPUTER-SIMULATION; GOLD NANOPARTICLES; QUANTUM DOTS; POLYMER MELT; INTERACTION POTENTIALS; ATOMISTIC SIMULATION; TIO2 NANOPARTICLES; REVERSE MICELLES AB A review of molecular dynamics simulation studies of nanoparticles is presented. While research on nanoparticles and their usage in industries, healthcare, and biomedical sciences has been very active, real time observation and analysis of some dynamical and thermodynamic properties and physical mechanisms underlying many of the special characteristics of various nanoparticles are not easily achieved experimentally. Due to the rapid development of the computational algorithms and available computational resources to scientific researchers and relatively small sizes of nanoparticles, molecular dynamics (MD) simulations, together with other computational methods, occupy an increasingly important niche in this rapidly developing and expanding field. As part of the Annual Reports, the focus of this review is on the research published during the last year. A brief survey of fundamentals of MD simulations is given first, followed by how various MD methodologies are utilized for the investigations of the nucleation and melting behavior of various metallic nanoparticles, for the understanding of structural and physiochemical properties of metal oxide and semiconductor nanoparticles; and for the studies of interactions of nanoparticles with their surrounding materials and among themselves. The role of multiscale modeling, involving both methods and applications, in nanoparticle research is discussed. The challenges and opportunities in the future are briefly discussed at the end. C1 NIDDK, Genet & Biochem Branch, Bethesda, MD 20892 USA. RP Tian, P (reprint author), NIDDK, Genet & Biochem Branch, BLDG 5,Rm 201,5 Mem Dr, Bethesda, MD 20892 USA. NR 119 TC 17 Z9 17 U1 1 U2 14 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 0260-1826 J9 ANNU REP PROG CHEM C PY 2008 VL 104 BP 142 EP 164 DI 10.1039/b7030897f PG 23 WC Chemistry, Physical SC Chemistry GA BKA23 UT WOS:000267581000005 ER PT S AU Simon, MA Watson, J Baldwin, JT Wagner, WR Borovetz, HS AF Simon, Marc A. Watson, John Baldwin, J. Timothy Wagner, William R. Borovetz, Harvey S. TI Current and future considerations in the use of mechanical circulatory support devices SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING SE ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review; Book Chapter DE heart-assist device; heart failure ID VENTRICULAR ASSIST DEVICE; CHRONIC HEART-FAILURE; ISCHEMIC MITRAL REGURGITATION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; PERCUTANEOUS CORONARY INTERVENTION; CARDIAC-RESYNCHRONIZATION THERAPY; CONVERTING-ENZYME-INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; ARTERY-BYPASS-SURGERY; TUMOR-NECROSIS-FACTOR AB Heart failure (HF) is a major public health problem in the United States, and its prevalence is likely to increase with the aging U.S. population. Mechanical circulatory support (MCS) utilizing bladder-based blood pumps generating pulsatile flow has been reserved for patients with severe I-IF failing medical therapy. As MCS technology has advanced to include rotary blood pumps, so has our understanding of the biological and clinical responses to MCS, which in turn has altered the risk/benefit profile of this therapy. This may lead to paradigm shifts in device usage from support of end-stage I-IF to temporary support for recovery of cardiac function and earlier usage, to, ultimately, prevention of disease progression. This review serves to explore the current state and future opportunities of MCS within our larger understanding of the epidemiology pathophysiology, and treatment options for HF. C1 [Simon, Marc A.] Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA 15213 USA. [Simon, Marc A.; Wagner, William R.; Borovetz, Harvey S.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA. [Wagner, William R.; Borovetz, Harvey S.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Wagner, William R.] Univ Pittsburgh, Dept Chem Engn, Pittsburgh, PA 15213 USA. [Watson, John] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Baldwin, J. Timothy] NHLBI, Bethesda, MD 20892 USA. RP Simon, MA (reprint author), Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA 15213 USA. EM simonma@upmc.edu FU NCATS NIH HHS [UL1 TR000005, KL2 TR000146]; NCRR NIH HHS [KL2 RR 024154] NR 146 TC 10 Z9 10 U1 0 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 BN 978-0-8243-3510-6 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2008 VL 10 BP 59 EP 84 DI 10.1146/annurev.bioeng.9.060906.151856 PG 26 WC Engineering, Biomedical SC Engineering GA 340XW UT WOS:000258679300003 PM 18647112 ER PT S AU Zhou, HX Rivas, GN Minton, AP AF Zhou, Huan-Xiang Rivas, German Minton, Allen P. TI Macromolecular crowding and confinement: Biochemical, biophysical, and potential physiological consequences SO ANNUAL REVIEW OF BIOPHYSICS SE Annual Review of Biophysics LA English DT Review; Book Chapter DE excluded volume; configurational entropy; free energy; protein-protein interactions; protein folding; site-binding ID PROTEIN SELF-ASSOCIATION; AMYLOID FIBRIL FORMATION; LOCALLY PLANAR SURFACES; GLOBULAR-PROTEINS; ESCHERICHIA-COLI; EXCLUDED-VOLUME; MOLECULAR CONFINEMENT; RELAXATION DISPERSION; ADSORPTION EQUILIBRIA; ENZYME-ACTIVITY AB Expected and observed effects of volume exclusion on the free energy of rigid and flexible macromolecules in crowded and confined systems, and consequent effects of crowding and confinement on macromolecular reaction rates and equilibria are summarized. Findings from relevant theoretical/simulation and experimental literature published from 2004 onward are reviewed. Additional complexity arising from the heterogeneity of local environments in biological media, and the presence of nonspecific interactions between macromolecules over and above steric repulsion, are discussed. Theoretical and experimental approaches to the characterization of crowding and confinement-induced effects in systems approaching the complexity of living organisms are suggested. C1 [Zhou, Huan-Xiang] Florida State Univ, Dept Phys, Sch Computat Sci, Tallahassee, FL 32306 USA. [Zhou, Huan-Xiang] Florida State Univ, Dept Phys, Inst Mol Biophys, Tallahassee, FL 32306 USA. [Rivas, German] CSIC, Ctr Invest Biol, Dept Ciencia Prot, E-28040 Madrid, Spain. [Minton, Allen P.] NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Zhou, HX (reprint author), Florida State Univ, Dept Phys, Sch Computat Sci, Tallahassee, FL 32306 USA. EM zhou@sb.fsu.edu; grivas@cib.csic.es; minton@helix.nih.gov RI Zhou, Huan-Xiang/M-5170-2016; OI Zhou, Huan-Xiang/0000-0001-9020-0302; Minton, Allen/0000-0001-8459-1247; Rivas, German/0000-0003-3450-7478 FU Intramural NIH HHS [Z01 DK024957-01, Z01 DK024957-02, ZIA DK024957-03]; NIGMS NIH HHS [GM058187, R01 GM058187, R01 GM058187-09] NR 106 TC 839 Z9 849 U1 26 U2 303 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1936-122X BN 978-0-8243-1837-6 J9 ANNU REV BIOPHYS JI Ann. Rev. Biophys. PY 2008 VL 37 BP 375 EP 397 DI 10.1146/annurev.biophys.37.032807.125817 PG 23 WC Biophysics SC Biophysics GA 332UB UT WOS:000258107500019 PM 18573087 ER PT S AU Leibenluft, E Rich, BA AF Leibenluft, Ellen Rich, Brendan A. TI Pediatric bipolar disorder SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY SE Annual Review of Clinical Psychology LA English DT Review; Book Chapter DE children; severe mood dysregulation; diagnosis; functional magnetic resonance imaging; treatment ID DEFICIT HYPERACTIVITY DISORDER; SEVERE MOOD DYSREGULATION; VOXEL-BASED MORPHOMETRY; SOCIAL RHYTHM THERAPY; HOSPITALIZED AGGRESSIVE-CHILDREN; FAMILY-FOCUSED TREATMENT; SCHOOL-AGED CHILDREN; CONDUCT DISORDER; I-DISORDER; DOUBLE-BLIND AB In the past decade, interest in and research on pediatric bipolar disorder (BD) has increased substantially. Prevalence rates of the disorder have doubled in outpatient settings, while twice as many research articles on pediatric BD were published in the past five years as in the prior decade. This review focuses on recent developments in the study of pediatric BID. We examine current research on the diagnostic boundaries of BD in youths, in particular the issues of episodicity and irritability, and provide assessment guidelines. We review data elucidating the pathophysiology of pediatric BD, with a focus on how these results may inform diagnosis. Finally, we discuss treatment approaches for pediatric BD, particularly psychotherapeutic interventions. Throughout the review, we pay particular attention to youths with severe chronic irritability, hyperarousal, and hyper-reactivity, who reflect the population in whom the diagnosis of BD is most debated. C1 [Leibenluft, Ellen; Rich, Brendan A.] NIMH, NIH, Mood Anxiety Program,Dept Hlth & Human Serv, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), NIMH, NIH, Mood Anxiety Program,Dept Hlth & Human Serv, Sect Bipolar Spectrum Disorders, Bethesda, MD 20892 USA. EM leibs@mail.nih.gov; brendanrich@mail.nih.gov NR 117 TC 45 Z9 45 U1 5 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1548-5943 BN 978-0-8243-3904-3 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2008 VL 4 BP 163 EP 187 DI 10.1146/annurev.clinpsy.4.022007.141216 PG 27 WC Psychology, Clinical; Psychology SC Psychology GA 297WW UT WOS:000255649100008 PM 17716034 ER PT S AU Hunter, KW Crawford, NPS AF Hunter, Kent W. Crawford, Nigel P. S. TI The Future of Mouse QTL Mapping to Diagnose Disease in Mice in the Age of Whole-Genome Association Studies SO ANNUAL REVIEW OF GENETICS SE Annual Review of Genetics LA English DT Review; Book Chapter DE QTLs; whole-genome association; mouse models ID QUANTITATIVE TRAIT LOCI; CANCER SUSCEPTIBILITY GENE; WIDE ASSOCIATION; BREAST-CANCER; GERMLINE POLYMORPHISMS; COLLABORATIVE CROSS; LABORATORY MOUSE; HDL CHOLESTEROL; COMMON DISEASES; CANDIDATE GENES AB Genome-wide association analysis is emerging as a powerful tool to define novel genes and molecular pathways involved in susceptibility to human complex disorders. However, in spite of recent successes, this approach is not without its limitations, the most notable of which is inconsistent phenotype penetrance due to varied environmental exposures. Mouse models do, however, circumvent some of these drawbacks by allowing for a much higher degree of control over genetic variation and environmental exposure, and although their application to human complex genetics is not always straightforward, they do serve as a powerful means of complementing observations inhuman populations. Mouse quantitative trait locus mapping has proven a successful, yet technically demanding method for defining trait Susceptibility. In this review, we focus upon recent advances that, are both reducing the technical burden traditionally associated with quantitative trait locus mapping, and enhancing the applicability of these approaches to human disease. C1 [Hunter, Kent W.; Crawford, Nigel P. S.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov NR 63 TC 45 Z9 45 U1 5 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 BN 978-0-8243-1242-8 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2008 VL 42 BP 131 EP 141 DI 10.1146/annurev.genet.42.110807.091659 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 384TL UT WOS:000261767000006 PM 18759635 ER PT S AU Antonellis, A Green, ED AF Antonellis, Anthony Green, Eric D. TI The role of aminoacyl-tRNA synthetases in genetic diseases SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE Charcot-Marie-Tooth disease; neurodegeneration; peripheral; neuropathy; protein synthesis; translation ID MARIE-TOOTH-DISEASE; SPINAL MUSCULAR-ATROPHY; PROTEIN-SYNTHESIS; CORD INVOLVEMENT; BINDING DOMAIN; CHROMOSOME 7P; BRAIN-STEM; GARS GENE; MITOCHONDRIAL; MUTATIONS AB Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes responsible for performing the first step of protein synthesis. Specifically, ARSs attach amino acids to their cognate tRNA. molecules in the cytoplasm and mitochondria. Recent studies have demonstrated that mutations in genes encoding ARSs can result in neurodegeneration, raising many questions about the role of these enzymes (and protein synthesis in general) in neuronal function. In this review, we summarize the current knowledge of genetic diseases that are associated with mutations in ARS-encoding genes, discuss the potential pathogenic mechanisms underlying these disorders, and point to likely areas of future research that will advance our understanding about the role of ARSs in genetic diseases. C1 [Antonellis, Anthony; Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Antonellis, A (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM cgreen@nhgri.nih.gov FU NINDS NIH HHS [R00 NS060983] NR 49 TC 100 Z9 103 U1 2 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3709-4 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2008 VL 9 BP 87 EP 107 DI 10.1146/annurev.genom.9.081307.164204 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA 354HG UT WOS:000259629000005 PM 18767960 ER PT S AU Huizing, M Helip-Wooley, A Westbroek, W Gunay-Aygun, M Gahl, WA AF Huizing, Marjan Helip-Wooley, Amanda Westbroek, Wendy Gunay-Aygun, Meral Gahl, William A. TI Disorders of lysosome-related organelle biogenesis: Clinical and molecular genetics SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE Chediak-Higashi syndrome; Griscelli syndrome; Hermansky-Pudlak syndrome; melanosome; platelet ID HERMANSKY-PUDLAK-SYNDROME; CHEDIAK-HIGASHI-SYNDROME; STORAGE-POOL DEFICIENCY; PLATELET-DENSE GRANULES; MELANOCYTE-SPECIFIC PROTEINS; ABSENT RADIUS SYNDROME; MYOSIN-VA; INTERMEDIATE-FILAMENTS; MULTIVESICULAR BODIES; TYPE-2 PNEUMOCYTES AB Lysosome-related organelles (LROs) are a heterogeneous group of vesicles that share various features with lysosomes, but are distinct in function, morphology, and composition. The biogenesis of LROs employs a common machinery, and genetic defects in this machinery can affect all LROs or only an individual LRO, resulting in a variety of clinical features. In this review, we discuss the main components of LRO biogenesis. We also summarize the function, composition, and resident cell types of the major LROs. Finally, we describe the clinical characteristics of the major human LRO disorders. C1 [Huizing, Marjan] NHGRI, Cell Biol Metab Disorders Unit, NIH, Bethesda, MD 20892 USA. [Helip-Wooley, Amanda; Westbroek, Wendy; Gunay-Aygun, Meral; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Huizing, M (reprint author), NHGRI, Cell Biol Metab Disorders Unit, NIH, Bethesda, MD 20892 USA. EM mhuizing@mail.nih.gov; ahwooley@mail.nih.gov; wwestbro@mail.nih.gov; mgaygun@mail.nih.gov; bgahl@helix.nih.gov FU National Human Genome Research Institute (NHGRI); National Institutes of Health, Bethesda, Maryland, USA FX This work was supported by the Intramural Research program of the National Human Genome Research Institute (NHGRI), National Institutes of Health, Bethesda, Maryland, USA. NR 131 TC 160 Z9 165 U1 1 U2 16 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3709-4 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2008 VL 9 BP 359 EP 386 DI 10.1146/annurev.genom.9.081307.164303 PG 28 WC Genetics & Heredity SC Genetics & Heredity GA 354HG UT WOS:000259629000019 PM 18544035 ER PT S AU Spolski, R Leonard, WJ AF Spolski, Rosanne Leonard, Warren J. TI Interleukin-21: Basic biology and implications for cancer and autoimmunity SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE cytokine; Blimp-1; plasma cell differentiation; Stat3; antitumor; adaptive immunity; innate immunity ID RECEPTOR-GAMMA-CHAIN; CD8(+) T-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; ANTI-DR5 ANTIBODY THERAPY; NATURAL-KILLER-CELLS; MEMORY B-CELLS; NK CELLS; IN-VIVO; IL-21 RECEPTOR; CYTOKINE RECEPTOR AB Interleukin-21 (IL-21), a potent immunomodulatory four-alpha-helical-bundle type I cytokine, is produced by NKT and CD(4+) T cells and has pleiotropic effects on both innate and adaptive immune responses. These actions include positive effects such as enhanced proliferation of lymphoid cells, increased cytotoxicity of CD(8+) T cells and natural killer (NK) cells, and differentiation of B cells into plasma cells. Conversely, IL-21 also has direct inhibitory effects on the antigen-presenting function of dendritic cells and can be proapoptotic for B cells and NK cells. IL-21 is also produced by Th17 cells and is a critical regulator of Th17 development. The regulatory activity of IL-21 is modulated by the differentiation state of its target cells as well as by other cytokines or costimulatory molecules. IL-21 has potent antitumor activity but is also associated with the development of autoimmune disease. IL-21 transcription is dependent on a calcium signal and NFAT sites, and IL-21 requires Stat3 for its signaling. The key to harnessing the power of IL-21 will depend on better understanding its range of biological actions, its mechanism of action, and the molecular basis of regulation of expression of IL-21 and its receptor. C1 [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Spolski, R (reprint author), NHLBI, Lab Mol Immunol, Bldg 10, Bethesda, MD 20892 USA. EM spolskir@nhlbi.nih.gov; wjl@helix.nih.gov FU Intramural NIH HHS NR 90 TC 381 Z9 409 U1 0 U2 32 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3026-2 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2008 VL 26 BP 57 EP 79 DI 10.1146/annurev.immunol.26.021607.090316 PG 23 WC Immunology SC Immunology GA 293QH UT WOS:000255349300003 PM 17953510 ER PT S AU Copeland, WC AF Copeland, William C. TI Inherited mitochondrial diseases of DNA replication SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE DNA polymerase gamma; nucleotide pools; mitochondrial DNA depletion syndrome; progressive external ophthalmoplegia; ataxia-neuropathy ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; THYMIDINE PHOSPHORYLASE-DEFICIENCY; PROBABLE GERMLINE MOSAICISM; POLYMERASE-GAMMA MUTATIONS; ALPERS-SYNDROME; SACCHAROMYCES-CEREVISIAE; DEOXYGUANOSINE KINASE; MULTIPLE DELETIONS; DEPLETION SYNDROME; POLG MUTATIONS AB Mitochondrial genetic diseases can result from defects in mitochondrial DNA (mtDNA) in the form of deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These mutations may be spontaneous, maternally inherited, or a result of inherited nuclear defects in genes that maintain mtDNA. This review focuses on our current understanding of nuclear gene mutations that produce mtDNA alterations and cause mitochondrial depletion syndrome (MDS), progressive external ophthalmoplegia (PEO), ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). To date, all of these etiologic nuclear genes fall into one of two categories: genes whose products function directly at the mtDNA replication fork, such as POLG, POLG2, and TWINKLE, or genes whose products supply the mitochondria with deoxynucleotide triphosphate pools needed for DNA replication, such as TK2, DGUOK, TP, SUCLA2, ANT1, and possibly the newly identified MPV17. C1 [Copeland, William C.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM copelanl@nichs.nih.gov FU Intramural NIH HHS [Z01 ES065078-14] NR 84 TC 171 Z9 176 U1 1 U2 22 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0559-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2008 VL 59 BP 131 EP 146 DI 10.1146/annurev.med.59.053006.104646 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 265YJ UT WOS:000253397600009 PM 17892433 ER PT S AU Garantziotis, S Hollingsworth, JW Zaas, AK Schwartz, DA AF Garantziotis, Stavros Hollingsworth, John W. Zaas, Aimee K. Schwartz, David A. TI The effect of toll-like receptors and toll-like receptor genetics in human disease SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE innate immunity; toll-like receptors; genomics; gene-environment interactions ID TOLL-LIKE-RECEPTOR-4 ASP299GLY POLYMORPHISM; RESPIRATORY SYNCYTIAL VIRUS; INFLAMMATORY-BOWEL-DISEASE; ACUTE ALLOGRAFT-REJECTION; STOP CODON POLYMORPHISM; HUMAN DENDRITIC CELLS; INNATE IMMUNE-SYSTEM; PROSTATE-CANCER RISK; SEQUENCE VARIANTS; ENDOTOXIN EXPOSURE AB Toll-like receptors (TLRs) enable innate immune recognition of endogenous and exogenous prototypic ligands. They also orchestrate innate and adaptive immune response to infection, inflammation, and tissue injury. Given their significance in the immune response, it is not surprising that genetic variations of TLRs can affect their function and by extension affect the response of the organism to environmental stimuli. The genetics of TLRs provides important insights in gene-environment interactions in health and disease, and it may enable scientists to assess patients' susceptibility to diseases or predict their response to treatments. C1 [Garantziotis, Stavros; Hollingsworth, John W.; Zaas, Aimee K.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Garantziotis, Stavros; Schwartz, David A.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Garantziotis, S (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. EM garan001@uc.duke.edu; john.hollingsworth@duke.edu; aimee.zais@duke.edu; david.schwartz@nielis.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural NIH HHS; NHLBI NIH HHS [HL91335]; NIAID NIH HHS [5AI065837, AI58161]; NIEHS NIH HHS [ES11961] NR 92 TC 42 Z9 44 U1 0 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0559-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2008 VL 59 BP 343 EP 359 DI 10.1146/annurev.med.59.061206.112455 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 265YJ UT WOS:000253397600024 PM 17845139 ER PT S AU Potrykus, K Cashel, M AF Potrykus, Katarzyna Cashel, Michael TI (p)ppGpp: Still Magical? SO ANNUAL REVIEW OF MICROBIOLOGY SE Annual Review of Microbiology LA English DT Review; Book Chapter DE stringent response; transcription; stress; pathogenesis; Rel/Spo; homologs ID RIBOSOMAL-RNA TRANSCRIPTION; BACTERIAL SIGNAL MOLECULE; ESCHERICHIA-COLI; STRINGENT RESPONSE; BACILLUS-SUBTILIS; GUANOSINE TETRAPHOSPHATE; SECONDARY CHANNEL; GENE-EXPRESSION; PPGPP SYNTHESIS; IN-VITRO AB The fundamental details of how nutritional stress leads to elevating (p)ppGpp are questionable. By common usage, the meaning of the stringent response has evolved from the specific response to (p)ppGpp provoked by amino acid starvation to all responses caused by elevating (p)ppGpp by any means. Different responses have similar as well as dissimilar positive and negative effects on gene expression and metabolism. The different ways that different bacteria seem to exploit their capacities to form and respond to (p)ppGpp are already impressive despite an early stage of discovery. Apparently, (p)ppGpp can contribute to regulation of many aspects of microbial cell biology that are sensitive to changing nutrient availability: growth, adaptation, secondary metabolism, survival, persistence, cell division, motility, biofilms, development, competence, and virulence. Many basic questions still exist. This review tries to focus on some issues that linger even for the most widely characterized bacterial strains. C1 [Potrykus, Katarzyna; Cashel, Michael] NICHHD, NIH, Mol Genet Lab, Bethesda, MD 20892 USA. RP Potrykus, K (reprint author), NICHHD, NIH, Mol Genet Lab, Bethesda, MD 20892 USA. EM potrykuk@mail.nih.gov; mcashel@nih.gov FU NIH FX We thank Daniel Vinella, Agnieszka Szalewska-Palasz, Rajendran Harinarayanan, Helen Murphy, and the Friday Seminar group for many discussions. We apologize to coauthors and colleagues whose important citations are absent owing to space limitations. This work was supported by the NICHD intramural program of the NIH. NR 85 TC 464 Z9 474 U1 13 U2 95 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 BN 978-0-8243-1162-9 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2008 VL 62 BP 35 EP 51 DI 10.1146/annurev.micro.62.081307.162903 PG 17 WC Microbiology SC Microbiology GA 359EA UT WOS:000259968000004 PM 18454629 ER PT S AU Best, SM AF Best, Sonja M. TI Viral Subversion of Apoptotic Enzymes: Escape from Death Row SO ANNUAL REVIEW OF MICROBIOLOGY SE Annual Review of Microbiology LA English DT Review; Book Chapter DE caspase inhibition; serine protease; CrmA; p35; IAP; vFLIP ID CYTOKINE RESPONSE MODIFIER; NF-KAPPA-B; INTERLEUKIN-1-BETA CONVERTING-ENZYME; EVOLUTIONARILY CONSERVED MECHANISM; HUMAN-PAPILLOMAVIRUS TYPE-16; MINK DISEASE PARVOVIRUS; CASPASE INHIBITOR P35; CYTOCHROME-C RELEASE; MYXOMA-VIRUS SERP2; CELL-DEATH AB To prolong cell viability and facilitate replication, viruses have evolved multiple mechanisms to inhibit the host apoptotic response. Cellular proteases such as caspases and serine proteases are instrumental in promoting apoptosis. Thus, these enzymes are logical targets for virus-mediated modulation to suppress cell death. Four major classes of viral inhibitors antagonize caspase function: serpins, p35 family members, inhibitor of apoptosis proteins, and viral FLICE-inhibitory proteins. Viruses also subvert activity of the serine proteases, granzyme B and HtrA2/Omi, to avoid cell death. The combined efforts of viruses to suppress apoptosis suggest that this response should be avoided at all costs. However, some viruses utilize caspases during replication to aid virus protein maturation, progeny release, or both. Hence, a multifaceted relationship exists between viruses and the apoptotic response they induce. Examination of these interactions contributes to our understanding of both virus pathogenesis and the regulation of apoptotic enzymes in normal cellular functions. C1 NIAID, Rocky Mt Lab, NIH, Lab Presistent Viral Dis, Hamilton, MT 59840 USA. RP Best, SM (reprint author), NIAID, Rocky Mt Lab, NIH, Lab Presistent Viral Dis, Hamilton, MT 59840 USA. EM sbest@niaid.nih.gov FU National Institute of Allergy and Infections Diseases, National Institutes of Health. FX Thank you to Marshall Bloom, Dana Mitzel, Shelly Robertson, Travis Taylor, and Dan Voth for critique of the manuscript and to Anita Mora for graphical expertise. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infections Diseases, National Institutes of Health. NR 142 TC 93 Z9 96 U1 0 U2 11 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 BN 978-0-8243-1162-9 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2008 VL 62 BP 171 EP 192 DI 10.1146/annurev.micro.62.081307.163009 PG 22 WC Microbiology SC Microbiology GA 359EA UT WOS:000259968000011 PM 18729734 ER PT S AU Holmes, EC AF Holmes, Edward C. TI Evolutionary History and Phylogeography of Human Viruses SO ANNUAL REVIEW OF MICROBIOLOGY SE Annual Review of Microbiology LA English DT Review; Book Chapter DE evolution; phylogeny; coalescent; emergence; epidemic ID HEPATITIS-B-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN POLYOMAVIRUS JC; RNA VIRUSES; MOLECULAR EPIDEMIOLOGY; INFECTIOUS-DISEASES; GENETIC DIVERSITY; SPONTANEOUS MUTATION; POPULATION HISTORY; HUMAN MIGRATIONS AB Understanding the evolutionary history of human viruses, along with the factors that have shaped their spatial distributions, is one of the most active areas of study in the field of microbial evolution. I give an overview of our current knowledge of the genetic diversity of human viruses using comparative studies of viral populations, particularly those with RNA genomes, to highlight important generalities in the patterns and processes of viral evolution. Special emphasis is given to the major dichotomy between RNA and DNA viruses in their epidemiological dynamics and the different types of phylogeographic pattern exhibited by human viruses. I also consider a central paradox in studies of viral evolution: Although epidemiological theory predicts that RNA viruses have ancestries dating back millennia, with major ecological transitions facilitating their emergence, the genetic diversity in currently circulating viral populations has a far more recent ancestry, indicative of continual lineage turnover. C1 [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. EM ech15@psu.edu OI Holmes, Edward/0000-0001-9596-3552 NR 142 TC 103 Z9 104 U1 0 U2 28 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 BN 978-0-8243-1162-9 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2008 VL 62 BP 307 EP 328 DI 10.1146/annurev.micro.62.081307.162912 PG 22 WC Microbiology SC Microbiology GA 359EA UT WOS:000259968000018 PM 18785840 ER PT S AU Sommer, MA Wurtz, RH AF Sommer, Marc A. Wurtz, Robert H. TI Brain circuits for the internal monitoring of movements SO ANNUAL REVIEW OF NEUROSCIENCE SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE vision; saccadic eye movements; corollary discharge; efference copy; perception ID FRONTAL EYE FIELD; UPDATING SPATIAL REPRESENTATIONS; COROLLARY DISCHARGE DYSFUNCTION; LATERAL INTRAPARIETAL AREA; INDUCED STIMULUS MOVEMENT; VISUAL RECEPTIVE-FIELDS; HUMAN PARIETAL CORTEX; SUPERIOR COLLICULUS; EFFERENCE COPY; DYNAMIC CIRCUITRY AB Each movement we make activates our own sensory receptors, thus causing a problem for the brain: the spurious, movement-related sensations must be discriminated from the sensory inputs that really matter, those representing our environment. Here we consider circuits for solving this problem in the primate brain. Such circuits convey a copy of each motor command, known as a corollary discharge (CD), to brain regions that use sensory input. In the visual system, CD signals may help to produce a stable visual percept from the jumpy images resulting from our rapid eye movements. A candidate pathway for providing CD for vision ascends from the superior colliculus to the frontal cortex in the primate brain. This circuit conveys warning signals about impending eye movements that are used for planning subsequent movements and analyzing the visual world. Identifying this circuit has provided a model for studying CD in other primate sensory systems and may lead to a better understanding of motor and mental disorders. C1 [Sommer, Marc A.] Univ Pittsburgh, Ctr Neural Basis Cognit, Dept Neurosci, Pittsburgh, PA 15260 USA. [Sommer, Marc A.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. [Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sommer, MA (reprint author), Univ Pittsburgh, Ctr Neural Basis Cognit, Dept Neurosci, Pittsburgh, PA 15260 USA. EM masommer@pitt.edu; bob@lsr.nei.nih.gov FU Intramural NIH HHS [Z01 EY000109-28]; NEI NIH HHS [R01 EY017592, EY017592] NR 81 TC 217 Z9 218 U1 5 U2 30 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X BN 978-0-8243-2431-5 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2008 VL 31 BP 317 EP 338 DI 10.1146/annurev.neuro.31.060407.125627 PG 22 WC Neurosciences SC Neurosciences & Neurology GA 331DF UT WOS:000257992200014 PM 18558858 ER PT S AU Taubenberger, JK Morens, DM AF Taubenberger, Jeffery K. Morens, David M. TI The pathology of influenza virus infections SO ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE pandemic; pneumonia; bronchitis; alveolitis; 1918 influenza; H5N1 ID HONG-KONG INFLUENZA; A H5N1 VIRUS; PANDEMIC INFLUENZA; REASSORTANT VIRUS; RESPIRATORY-TRACT; SQUIRREL-MONKEYS; ASIAN INFLUENZA; LUNG-BIOPSY; GENE; PNEUMONIA AB Influenza viruses are significant human respiratory pathogens that cause both seasonal, endemic infections and periodic, unpredictable pandemics. The worst pandemic on record, in 1918, killed approximately 50 million people worldwide. Human infections caused by H5N1 highly pathogenic avian influenza viruses have raised concern about the emergence of another pandemic. The histopathology of fatal influenza virus pneumonias as documented over the past 120 years is reviewed here. Strikingly, the spectrum of pathologic changes described in the 1918 influenza pandemic is not significantly different from the histopathology observed in other less lethal pandemics or even in deaths occurring during seasonal influenza outbreaks. C1 [Taubenberger, Jeffery K.; Morens, David M.] NIAID, NIH, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov; dmorens@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000995-01] NR 111 TC 307 Z9 321 U1 8 U2 69 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1553-4006 BN 978-0-8243-4303-3 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech. Dis. PY 2008 VL 3 BP 499 EP 522 DI 10.1146/annurev.pathol.3.121806.154316 PG 24 WC Pathology SC Pathology GA 275QD UT WOS:000254085800019 PM 18039138 ER PT S AU Vasiliou, V Gonzalez, FJ AF Vasiliou, Vasills Gonzalez, Frank J. TI Role of CYP1B1 in glaucoma SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE CYP; mutations; eye; transgenic mouse model; metabolism; steroids; arachidonic acid; retinoic acid; melatonin ID OPEN-ANGLE GLAUCOMA; PRIMARY CONGENITAL GLAUCOMA; CYTOCHROME P4501B1 CYP1B1; N-ACETYLTRANSFERASE ACTIVITY; ANTERIOR SEGMENT DYSGENESIS; HUMAN TRABECULAR MESHWORK; WIDE SCAN MAPS; INTRAOCULAR-PRESSURE; RETINOIC ACID; ARACHIDONIC-ACID AB Glaucoma is a leading cause of blindness, estimated to affect 60 million people by 2010, and represents a heterogeneous group of neurodegenerative disease. The two major types of glaucoma include primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG). A genetically heterogeneous group of developmental disorders known as anterior segment dysgenesis (ASD) have been reported to be associated with increased intraocular pressure (IOP) and glaucoma. These include Peters' anomaly, Rieger's anomaly, aniridia, iris hypoplasia, and iridogoniodysgenesis. Genetic linkage analysis and mutation studies have identified CYP1Bt as a causative gene in PCG, as a modifier gene in POAG, and, on rare occasions, as causative gene in POAG as well as in several ASD disorders. CYP1B1-deficient mice exhibit abnormalities in their ocular drainage structure and trabecular meshwork that are similar to those reported in human PCG patients. Accordingly, it is speculated that diminished or absent metabolism of key endogenous CYP1B1 substrates adversely affects the development of the trabecular meshwork. CYP1B1 protein is involved in the metabolism of steroids, retinol and retinal, arachidonate, and melatonin. The conserved expression of CYP1B1 in both murine and human eyes, its higher expression in fetal than adult eyes, and its biochemical properties are consistent with this hypothesis. The exact role of CYP1B1 in the pathogenesis of glaucoma and other ASD disorders remains to be elucidated. C1 [Vasiliou, Vasills] Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Mol Toxicol & Environm Hlth Sci Program, Denver, CO 80262 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Canc Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Vasiliou, V (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Mol Toxicol & Environm Hlth Sci Program, 4200 E 9th Ave, Denver, CO 80262 USA. EM vasilis.vasiliou@uchsc.edu; figonz@helix.nih.gov FU NEI NIH HHS [EY 11490] NR 148 TC 79 Z9 83 U1 1 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 BN 978-0-8243-0447-8 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2008 VL 48 BP 333 EP 358 DI 10.1146/annurev.pharmtox.48.061807.154729 PG 26 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 265YD UT WOS:000253396900013 PM 17914928 ER PT S AU Hall, MD Okabe, M Shen, DW Liang, XJ Gottesman, MM AF Hall, Matthew D. Okabe, Mitsunorl Shen, Ding-Wu Liang, Xing-Jie Gottesman, Michael M. TI The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE cisplatin; carboplatin; resistance; cellular accumulation; drug uptake ID OVARIAN-CARCINOMA CELLS; COPPER TRANSPORTER CTR1; ADENOSINE-TRIPHOSPHATASE ATP7B; CISPLATIN-RESISTANT CELLS; ENERGY-DEPENDENT UPTAKE; CASSETTE SUPERFAMILY TRANSPORTER; ORGANIC CATION TRANSPORTERS; METHIONINE-RICH CLUSTERS; L1210 LEUKEMIA-CELLS; DNA ADDUCT FORMATION AB The platinum (Pt) drugs cisplatin and carboplatin are heavily employed in chemotherapy regimens; however, similar to other classes of drugs, a number of intrinsic and acquired resistance mechanisms hamper their effectiveness. The method by which Pt drugs enter cells has traditionally been attributed to simple passive diffusion. However, recent evidence suggests a number of active uptake and efflux mechanisms are at play, and altered regulation of these transporters is responsible for the reduced accumulation of drug in resistant cells. This review suggests a model that helps reconcile the disparate literature by describing multiple pathways for Pt-containing drugs into and out of the cell. C1 [Hall, Matthew D.; Okabe, Mitsunorl; Shen, Ding-Wu; Liang, Xing-Jie; Gottesman, Michael M.] NCI, Natl Inst Hlth, Cell Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Natl Inst Hlth, Cell Biol Lab, Bethesda, MD 20892 USA. EM mgottesm.in@nih.gov RI Hall, Matthew/B-2132-2010 FU Intramural NIH HHS NR 209 TC 227 Z9 235 U1 8 U2 58 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 BN 978-0-8243-0447-8 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2008 VL 48 BP 495 EP 535 DI 10.1146/annurev.pharmtox.48.080907.180426 PG 41 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 265YD UT WOS:000253396900018 PM 17937596 ER PT J AU Rasaiah, JC Garde, S Hummer, G AF Rasaiah, Jayendran C. Garde, Shekhar Hummer, Gerhard TI Water in nonpolar confinement: From nanotubes to proteins and beyond SO ANNUAL REVIEW OF PHYSICAL CHEMISTRY SE Annual Review of Physical Chemistry LA English DT Review; Book Chapter DE nanofluidics; nanopores; hydrophobic effect; nanoscale drying transitions; protein hydration; proton transfer; confined fluids ID MOLECULAR-DYNAMICS SIMULATIONS; HIGH-PRESSURE CRYSTALLOGRAPHY; ALIGNED CARBON NANOTUBES; HEME-COPPER OXIDASES; ICE-NANOTUBES; LIQUID WATER; PROTON TRANSLOCATION; CYTOCHROME P450CAM; ELECTRIC-FIELD; ION-TRANSPORT AB Water molecules confined to nonpolar pores and cavities of nanoscopic dimensions exhibit highly unusual properties. Water filling is strongly cooperative, with the possible coexistence of filled and empty states and sensitivity to small perturbations of the pore polarity and solvent conditions. Confined water molecules form tightly hydrogen-bonded wires or clusters. The weak attractions to the confining wall, combined with strong interactions between water molecules, permit exceptionally rapid water flow, exceeding expectations from macroscopic hydrodynamics by several orders of magnitude. The proton mobility along 1D water wires also substantially exceeds that in the bulk. Proteins appear to exploit these unusual properties of confined water in their biological function (e.g., to ensure rapid water flow in aquaporins or to gate proton flow in proton pumps and enzymes). The unusual properties of water in nonpolar confinement are also relevant to the design of novel nanofluidic and molecular separation devices or fuel cells. C1 [Rasaiah, Jayendran C.] Univ Maine, Dept Chem, Orono, ME 04469 USA. [Garde, Shekhar] Rensselaer Polytech Inst, Howard P Isermann Dept Chem & Biol Engn, Troy, NY 12180 USA. [Hummer, Gerhard] NIDDK, Chem Phys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Rasaiah, JC (reprint author), Univ Maine, Dept Chem, Orono, ME 04469 USA. EM rasaiah@maine.edu; gardes@rpi.edu; gerhard.hummer@nih.gov RI Garde, Shekhar/C-3060-2008; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS NR 152 TC 371 Z9 374 U1 23 U2 266 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-426X J9 ANNU REV PHYS CHEM JI Annu. Rev. Phys. Chem. PY 2008 VL 59 BP 713 EP 740 DI 10.1146/annurev.physchem.59.032607.093815 PG 28 WC Chemistry, Physical SC Chemistry GA 298YR UT WOS:000255723500028 PM 18092942 ER PT S AU Kessler, RC Wang, PS AF Kessler, Ronald C. Wang, Philip S. TI The descriptive epidemiologv of commonly occurring mental disorders in the United States SO ANNUAL REVIEW OF PUBLIC HEALTH SE Annual Review of Public Health LA English DT Review; Book Chapter DE mental illness; prevalence; comorbidity; age of onset; illness burden ID NATIONAL-COMORBIDITY-SURVEY; WORLD-HEALTH-ORGANIZATION; INTERNATIONAL DIAGNOSTIC INTERVIEW; REPLICATION NCS-R; DSM-IV DISORDERS; AGE-OF-ONSET; GENERAL-POPULATION; PSYCHIATRIC-DISORDERS; CATCHMENT-AREA; DRUG-USE AB Data are reviewed on the descriptive epidemiology of commonly occurring DSM-IV mental disorders in the United States. These disorders are highly prevalent: Roughly half the population meets criteria for one or more such disorders in their lifetimes, and roughly one fourth of the population meets criteria in any given year. Most people with a history of mental disorder had first onsets in childhood or adolescence. Later onsets typically involve comorbid disorders. Some anxiety disorders (phobias, separation anxiety disorder) and impulse-control disorders have the earliest age of onset distributions. Other anxiety disorders (panic disorder, generalized anxiety disorder, post-traumatic stress disorder), mood disorders, and substance disorders typically have later ages of onset. Given that most seriously impairing and persistent adult mental disorders are associated with child-adolescent onsets and high comorbidity, increased efforts are needed to study the public health implications of early detection and treatment of initially mild and currently largely untreated child-adolescent disorders. C1 [Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Wang, Philip S.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu; wangphi@mail.nih.gov FU FIC NIH HHS [R03 TW 006481]; NIDA NIH HHS [R01 DA 016558]; NIMH NIH HHS [R01 MH 070884, R13 MH 066849, R01 MH 069864, U01 MH 60220] NR 54 TC 243 Z9 247 U1 6 U2 47 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 BN 978-0-8243-2729-3 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2008 VL 29 BP 115 EP 129 DI 10.1146/annurev.publhealth.29.020907.090847 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 293QI UT WOS:000255349400011 PM 18348707 ER PT J AU Norton, JT Witsch, MA Luong, L Kawamura, A Ghosh, S Stack, MS Sim, E Avram, MJ Appella, DH Huang, S AF Norton, John T. Witsch, Mark A. Luong, Lynn Kawamura, Akane Ghosh, Supurna Stack, M. Sharon Sim, Edith Avram, Michael J. Appella, Daniel H. Huang, Sui TI Synthesis and anticancer activities of 6-amino amonafide derivatives SO ANTI-CANCER DRUGS LA English DT Article DE amonafide; N-acetyl-transferese 2; numonafide; perinucleolar compartment ID ADVANCED BREAST-CANCER; LEUKEMIA GROUP-B; TOPOISOMERASE-II; PERINUCLEOLAR COMPARTMENT; ACETYLATOR PHENOTYPE; ANTITUMOR-ACTIVITY; DNA CLEAVAGE; BENZ(DE)ISOQUINOLIN-1,3-DIONES; PHARMACOKINETICS; CYTOTOXICITY AB Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical development for the treatment of neoplastic diseases. Amonafide contains a free arylamine, which causes it to be metabolized in humans by N-acetyl transferase-2 (NAT2) into a toxic form. To eliminate the NAT2 acetylation of amonafide while retaining the anticancer properties, we have synthesized nine derivatives that are structurally similar to amonafide that should not be acetylated. Eight derivatives have arylamines at the 6-position (vs. 5-position of amonafide) and one derivative completely lacks the arylamine. The derivative with a free amine in the 6-position and one with a substituted amine in the 6-position are not acetylated, whereas amonafide is extensively acetylated as determined by an NAT2 assay. The biological activities of these compounds were evaluated to determine whether they behaved similarly to amonafide in purified systems and in vitro. We found that three compounds had similar cancer cell-selective growth inhibition to amonafide, while retaining similar subcellular localization, DNA intercalation and topoisomerase 11 inhibition activities. In addition, these compounds were able to eliminate a marker of metastatic potential, the perinucleolar compartment. These three compounds (named numonafides) might thus allow for better patient management than those treated with amonafide; hence, they should be developed further as potential clinical replacements for amonafide or as novel anticancer drugs. C1 [Norton, John T.; Ghosh, Supurna; Stack, M. Sharon; Huang, Sui] Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. [Luong, Lynn; Avram, Michael J.] Northwestern Univ, Sch Med, Dept Anesthesiol, Chicago, IL 60611 USA. [Witsch, Mark A.; Appella, Daniel H.] Northwestern Univ, Dept Chem, Evanston, IL USA. [Witsch, Mark A.] NIDDK, Natl Inst Hlth, Bethesda, MD USA. [Kawamura, Akane; Sim, Edith] Univ Oxford, Dept Pharmacol, Oxford, England. RP Huang, S (reprint author), Northwestern Univ, Sch Med, Dept Cell & Mol Biol, 303 E Chicago Ave W11-240, Chicago, IL 60611 USA. EM s-huang2@northwestern.edu NR 28 TC 30 Z9 31 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JAN PY 2008 VL 19 IS 1 BP 23 EP 36 PG 14 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 241PQ UT WOS:000251668700004 PM 18043127 ER PT J AU Antachopoulos, C Meletiadis, J Sein, T Roilides, E Walsh, TJ AF Antachopoulos, Charalampos Meletiadis, Joseph Sein, Tin Roilides, Emmanuel Walsh, Thomas J. TI Comparative in vitro pharmacodynamics of caspofungin, micafungin, and anidulafungin against germinated and nongerminated Aspergillus conidia SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL ACTIVITY; FILAMENTOUS FUNGI; HUMAN PHAGOCYTES; ECHINOCANDIN; SUSCEPTIBILITY; FUMIGATUS; CANDIDA; MK-0991; VORICONAZOLE; FUSARIUM AB The concentration-dependent effects of echinocandins on the metabolic activity of Aspergillus spp. were comparatively studied by using nongerminated and germinated conidia. The susceptibilities of 11 Aspergillus fumigatus, 8 A. terreus and 8 A. flavus isolates to caspofungin, micafungin, and anidulafungin were studied by a CLSI (formerly NCCLS) M38-A broth microdilution-based method. After 48 h of incubation the minimum effective concentration (MEC) was defined microscopically. Metabolic activity was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay and modeled by using the sigmoid (E(max)) or "bell-shaped" model. The median MEC values of caspofungin (0.5 to 1 mu g/ml), micafungin (0.06 to 0.12 mu g/ml), and anidulafungin (0.03 mu g/ml) against nongerminated conidia increased by 0 to 1, 1 to 2, and 2 to 3 twofold dilutions, respectively (depending on the species), over those against germinated conidia. A similar shift to the right was demonstrated for the corresponding curves of metabolic activity. There was a significant correlation between the degrees of maximal metabolic inhibition caused by different echinocandins at both the species level (greater inhibition for A. flavus) and the strain level (r = 0.84 to 0.93; P < 0.0001). Paradoxical increases in metabolism in the presence of higher concentrations of caspofungin, micafungin, and anidulafungin were detected in 6, 2, and 5 of the A. fumigatus isolates, respectively; 5, 1, and 2 of the A. terreus isolates, respectively; and 1, 0, and 0 of the A. flavus isolates, respectively. Based on the model, 50% of the maximal paradoxical increase was detected with 4.2, 11.1, and 10.8 p,mu g/ml of caspofungin, micafungin, and anidulafungin, respectively. All echinocandins therefore exerted comparable levels of maximal metabolic inhibition against Aspergillus spp. at concentrations that were differentially increased for germinated versus nongerminated conidia. The paradoxical increase in metabolism occurred more frequently and at lower concentrations with caspofungin than with micafungin and anidulafungin. C1 [Antachopoulos, Charalampos; Meletiadis, Joseph; Sein, Tin; Roilides, Emmanuel; Walsh, Thomas J.] NCI, CRC, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. [Roilides, Emmanuel] Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, Thessaloniki, Greece. RP Walsh, TJ (reprint author), NCI, CRC, Pediat Oncol Branch, Immunocompromised Host Sect, Rm 1-5750,MSC 1100,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 33 TC 49 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2008 VL 52 IS 1 BP 321 EP 328 DI 10.1128/AAC.00699-07 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 248ED UT WOS:000252133700036 PM 17938191 ER PT J AU Marchand, C Beutler, JA Wamiru, A Budihas, S Mollmann, U Heinisch, L Mellors, JW Le Grice, SF Pommier, Y AF Marchand, Christophe Beutler, John A. Wamiru, Antony Budihas, Scott Moellmann, Ute Heinisch, Lothar Mellors, John W. Le Grice, Stuart F. Pommier, Yves TI Madurahydroxylactone derivatives as dual inhibitors of human immunodeficiency virus type 1 integrase and RNase H SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RIBONUCLEASE-H; REVERSE-TRANSCRIPTASE; HIV-1 INTEGRASE; ANTIFUNGAL ANTIBIOTICS; DIKETO ACID; BIOLOGICAL-ACTIVITIES; HYDROXYTROPOLONES; PHARMACOKINETICS; PRADIMICIN; GS-9137 AB A series of 29 madurahydroxylactone derivatives was evaluated for dual inhibition of human immunodeficiency virus type 1 (HIV-1) integrase and RNase H. While most of the compounds exhibited similar potencies for both enzymes, two of the derivatives showed 10- to 100-fold-higher selectivity for each enzyme, suggesting that distinct pharmacophore models could be generated. This study exemplifies the common and divergent structural requirements for the inhibition of two structurally related HIV-1 enzymes and demonstrates the importance of systematically screening for both integrase and RNase H when developing novel inhibitors. C1 [Marchand, Christophe; Pommier, Yves] NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Beutler, John A.; Wamiru, Antony] NCI, Canc Res Ctr, Mol Targets Dev Program, Frederick, MD USA. [Wamiru, Antony] SAIC, Frederick, MD USA. [Budihas, Scott; Le Grice, Stuart F.] NCI, Canc Res Ctr, HIV Drug Resistance Program, Frederick, MD USA. [Moellmann, Ute] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Mol & Appl Microbiol, Jena, Germany. [Heinisch, Lothar] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Biomol Chem, Jena, Germany. [Mellors, John W.] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA USA. RP Marchand, C (reprint author), NCI, Canc Res Ctr, Mol Pharmacol Lab, 37 Convent Dr,Bldg 37,Rm 5060, Bethesda, MD 20892 USA. EM marchand@nih.gov RI Beutler, John/B-1141-2009; Marchand, Christophe/D-8559-2016 OI Beutler, John/0000-0002-4646-1924; FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 20 TC 28 Z9 30 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2008 VL 52 IS 1 BP 361 EP 364 DI 10.1128/AAC.00883-07 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 248ED UT WOS:000252133700046 PM 17967911 ER PT J AU Bertognolio, S Derdelinckx, I Parker, M Fitzgibbon, J Fleury, H Peeters, M Schuurman, R Pillay, D Morris, L Tanuri, A Gershy-Damet, GM Nkengasong, J Gilks, CF Sutherland, D Sandstrom, P AF Bertognolio, Silvio Derdelinckx, Inge Parker, Monica Fitzgibbon, Joseph Fleury, Herve Peeters, Martin Schuurman, Rob Pillay, Deenan Morris, Lynn Tanuri, Amilcar Gershy-Damet, Guy-Michel Nkengasong, John Gilks, Charles F. Sutherland, Donald Sandstrom, Paul TI World Health Organization/HIVResNet drug resistance laboratory strategy SO ANTIVIRAL THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS RNA; DRIED BLOOD SPOTS; WHOLE-BLOOD; PLASMA; SURVEILLANCE; STABILITY; HIV; STORAGE; AMPLIFICATION; EPIDEMIOLOGY AB With rapidly increasing access to antiretroviral drugs globally, HIV drug resistance (HIVDR) has become a significant public health issue, This requires a coordinated and collaborative response from country level to international level to assess the extent of HIVDR and the establishment of efficient and evidence-based strategies to minimize its appearance and onward transmission. In parallel with the rollout of universal access to HIV treatment, countries are developing protocols based on the recommendations of the World Health Organization (WHO) to measure, at a population level, both transmitted HIVDR and HIVDR emerging during treatment. The WHO in collaboration with international experts (HIVResNet Laboratory Working Group), has developed a laboratory strategy, which has the overall goal of delivering quality-assured HIV genotypic results on specimens derived from the HIVDR surveys. The results will be used to help control the emergence and spread of drug resistance and to guide decision makers on antiretroviral therapy policy at national, regional and global level. The HIVDR Laboratory Strategy developed by the WHO includes several key aspects: the formation of a global network of national, regional and specialized laboratories accredited to perform HIVDR testing using a common set of WHO standard and performance indicators; recommendations of acceptable methods for collection, handling, shipment and storage of specimens in field conditions; and the provision of laboratory technical support, capacity building and quality assurance for network laboratories. The WHO/HIVResNet HIVDR Laboratory Network has been developed along the lines of other successful laboratory networks coordinated by the WHO. As of August 2007, assessment for accreditation has been conducted in 30 laboratories, covering the WHO's African, South-East Asia, Western Pacific, and the Caribbean Regions. C1 [Bertognolio, Silvio; Gilks, Charles F.; Sutherland, Donald] WHO, HIV Dept, CH-1211 Geneva, Switzerland. [Derdelinckx, Inge] Univ Med Ctr, Dept Virol, Utrecht, Netherlands. [Parker, Monica; Schuurman, Rob] New York State Dept Hlth, David Axelrod Inst, Albany, NY USA. [Fitzgibbon, Joseph] DDCSB, TRP, DAIDS, NIAID,NIH,DHHS, Bethesda, MD USA. [Fleury, Herve] Hop Pellegrin, Virol Lab, F-33076 Bordeaux, France. [Peeters, Martin] Retrovirus Lab, Programme SIDA IRD, Montpellier, France. [Pillay, Deenan] Hlth Protect Agcy Colindale, Ctr Infect, London, England. [Morris, Lynn] Natl Inst Communicable Dis, HIV AIDS Unit, Johannesburg, South Africa. [Tanuri, Amilcar] Cidade Univ, Mol Virol Lab, Rio De Janeiro, Brazil. [Gershy-Damet, Guy-Michel] WHO, WHO Reg Off Africa, Ouagadougou, Burkina Faso. [Nkengasong, John] Ctr Dis Control, Global Programme AIDS, Atlanta, GA USA. [Sandstrom, Paul] Publ Hlth Agcy Canada, Natl HIV & Retrovirol Labs, Ottawa, ON, Canada. RP Bertognolio, S (reprint author), WHO, HIV Dept, CH-1211 Geneva, Switzerland. EM bertagnolio@who.int RI Gilks, Charles/B-4184-2012; OI , Lynn/0000-0003-3961-7828 NR 26 TC 34 Z9 35 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 SU 2 BP 49 EP 57 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 310DF UT WOS:000256508400005 PM 18575191 ER PT J AU Melvin, AJ Kang, M Hitti, J Livingston, E Cohn, SE Stocker, V Ross, AC Watts, H McComsey, GA AF Melvin, Ann J. Kang, Minhee Hitti, Jane Livingston, Elizabeth Cohn, Susan E. Stocker, Vicki Ross, Allison C. Watts, Heather McComsey, Grace A. TI Cord blood lipids in infants born to HIV-1-infected women treated with combination antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Article ID HIV-INFECTED WOMEN; MITOCHONDRIAL DYSFUNCTION; PROTEASE INHIBITORS; SERUM-CHOLESTEROL; LIPOPROTEIN-CHOLESTEROL; DENSITY-LIPOPROTEIN; PERINATAL EXPOSURE; UNITED-STATES; BIRTH-WEIGHT; TERM-PERIOD AB Background: To investigate the protease inhibitor (PI) therapy in utero on cord blood lipids in infants born to mothers enrolled in AIDS Clinical Trials Group protocol 5084, a prospective, multi-centre, observational study of antiretroviral therapy (ART) during pregnancy. Methods: Clinical outcome was determined in 80 infants born to women treated with Pis and 73 infants born to women treated with other antiretrovirals during pregnancy. Cord blood serum from 117 of these infants was assayed for total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein All (apoA1), apolipoprotein B100 (apoB) and lipoprotein (a). Covariates considered in the analysis included race/ethnicity, gestational age, infant gender, infant birth weight, mode of delivery, maternal tobacco and alcohol use, post-partum body mass index, and ART duration. Results: Cord blood total and HDL cholesterol, triglyceride, apoA1, apoB, lipoprotein (a) and apoB/apoA1 ratio were not different between the two groups. Cord blood lipid levels in these HIV-exposed infants were similar to those reported in other neonatal cohorts. Controlling for race/ethnicity, infants born to women treated with Pis had higher LDL cholesterol than those born to women not treated with Pis (29 mg/dl versus 27 mg/dl, P=0.006). Conclusion: Only LDL cholesterol was significantly higher in the cord blood of PI-exposed infants versus those not exposed to Pis in utero. As the difference between the two groups was small, the clinical relevance of the effect of maternal PI treatment on infant LDL cholesterol levels at birth is not clear. C1 [Melvin, Ann J.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Kang, Minhee] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Hitti, Jane] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Livingston, Elizabeth] Duke Univ, Sch Med, Dept Obstet & Gynecol, Durham, NC USA. [Cohn, Susan E.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. [Stocker, Vicki] AIDS Clin Trials Grp Operat Ctr, Rockville, MD USA. [Ross, Allison C.; McComsey, Grace A.] Case Western Reserve Univ, Dept Pediat & Med, Cleveland, OH 44106 USA. [Watts, Heather] NICHHD, Adolescent & Maternal AIDS Branch, Rockville, MD USA. RP Melvin, AJ (reprint author), Univ Washington, Dept Pediat, Seattle, WA 98195 USA. EM ann.melvin@seattlechildrens.org FU NIAID NIH HHS [U01 AI27658, U01 AI38558, U01 AI068636, U01 AI41089]; NICHD NIH HHS [N01 HD33345] NR 35 TC 2 Z9 2 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 3 BP 349 EP 355 PG 7 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 310DE UT WOS:000256508300003 PM 18572747 ER PT J AU Das, K Bandwar, R White, KL Feng, JY Sarafianos, SG Tuske, S Tu, X Clark, AD Boyer, PL Gaffney, BL Jones, RA Miller, MD Hughes, SH Arnold, E AF Das, K. Bandwar, R. White, K. L. Feng, J. Y. Sarafianos, S. G. Tuske, S. Tu, X. Clark, A. D., Jr. Boyer, P. L. Gaffney, B. L. Jones, R. A. Miller, M. D. Hughes, S. H. Arnold, E. TI Structural basis for K65R function: tenofovir resistance, reduced nucleotide incorporation and excision antagonism SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Das, K.; Bandwar, R.; Sarafianos, S. G.; Tuske, S.; Tu, X.; Arnold, E.] Rutgers State Univ, CABM, Piscataway, NJ USA. [Das, K.; Bandwar, R.; Sarafianos, S. G.; Tuske, S.; Tu, X.; Boyer, P. L.; Arnold, E.] Rutgers State Univ, Dept Chem & Biol Chem, Piscataway, NJ USA. [White, K. L.; Feng, J. Y.] Gilead Sci Inc, Foster City, CA 94404 USA. [Boyer, P. L.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A44 EP A44 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100057 ER PT J AU Jacobson, DL Lindsey, JC Aldrovandi, GM Gordon, CM Heckman, B Zadzilka, A Sheeran, E Moye, J Borum, P Hardin, D Mulligan, K AF Jacobson, D. L. Lindsey, J. C. Aldrovandi, G. M. Gordon, C. M. Heckman, B. Zadzilka, A. Sheeran, E. Moye, J. Borum, P. Hardin, D. Mulligan, K. TI Total body and spine bone mineral density across Tanner stages in vertically HIV-infected compared with uninfected children and youth: preliminary results of PACTG1045 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY NOV 06-08, 2008 CL London, ENGLAND C1 [Jacobson, D. L.; Lindsey, J. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Aldrovandi, G. M.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Gordon, C. M.] Childrens Hosp, Boston, MA 02115 USA. [Heckman, B.; Zadzilka, A.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Sheeran, E.] Social & Sci Syst Inc, Silver Spring, MD USA. [Moye, J.] NICHHD, NIH, Bethesda, MD 20892 USA. [Borum, P.] Univ Florida, Gainesville, FL USA. [Hardin, D.] Ohio State Univ, Columbus, OH 43210 USA. [Mulligan, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 8 BP A27 EP A27 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 392ZR UT WOS:000262341200040 ER PT J AU Kearney, M Shao, W Maldarelli, F Margolick, J Daar, E Mellors, J Coffin, J Palmer, S AF Kearney, M. Shao, W. Maldarelli, F. Margolick, J. Daar, E. Mellors, J. Coffin, J. Palmer, S. TI HIV-1 recombination in patients infected with multiple HIV-1 variants from the same donor SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Kearney, M.; Shao, W.; Maldarelli, F.; Palmer, S.] NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA. [Margolick, J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Daar, E.] Univ Calif Los Angeles, Med Ctr, Div HIV Med, Los Angeles, CA 90024 USA. [Mellors, J.] Univ Pittsburgh, Dept Infect Dis, Pittsburgh, PA USA. [Coffin, J.] Tufts Univ, Boston, MA 02111 USA. [Palmer, S.] Swedish Inst Infect Dis Control, Dept Virol, Solna, Sweden. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A77 EP A77 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100088 ER PT J AU Larder, BA Wang, D Revell, AD Coe, D Torti, C Montaner, JSG Harris, M Lane, HC AF Larder, B. A. Wang, D. Revell, A. D. Coe, D. Torti, C. Montaner, J. S. G. Harris, M. Lane, H. C. TI Preliminary results of a prospective clinical study of the HIV resistance response database initiative's computational models as a treatment decision tool SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Larder, B. A.; Wang, D.; Revell, A. D.; Coe, D.] HIV Resistance Response Database Initiat, London, England. [Torti, C.] Univ Brescia, Brescia, Italy. [Montaner, J. S. G.; Harris, M.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Lane, H. C.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A108 EP A108 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100116 ER PT J AU Maldarelli, F Wiegand, A Palmer, S Urban, N Kearney, M Coffin, J Mellors, J AF Maldarelli, F. Wiegand, A. Palmer, S. Urban, N. Kearney, M. Coffin, J. Mellors, J. TI Intensification with efavirenz or lopinavir/ritonavir does not reduce residual HIV-1 viraemia in patients on standard antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Maldarelli, F.; Wiegand, A.; Palmer, S.; Urban, N.; Kearney, M.] NCI Frederick, HIV Drug Resistance Program, NIH, Bethesda, MD USA. [Coffin, J.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A79 EP A79 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100090 ER PT J AU Nikolenko, GN Delviks-Frankenberry, KA Boyer, PL Hughes, SH Coffin, JM Jere, A Pathak, VK AF Nikolenko, G. N. Delviks-Frankenberry, K. A. Boyer, P. L. Hughes, S. H. Coffin, J. M. Jere, A. Pathak, V. K. TI HIV-1 reverse transcriptase connection domain mutations reduce template RNA degradation and enhance nucleoside reverse transcriptase inhibitor excision SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Nikolenko, G. N.; Jere, A.; Pathak, V. K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Boyer, P. L.; Hughes, S. H.] NCI, Vector Design & Replicat Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Coffin, J. M.] NCI, Host Virus Interact Unit, HIV Drug Resistance Program, Frederick, MD 21701 USA. RI Delviks-Frankenberry, Krista/M-4822-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A60 EP A60 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100073 ER PT J AU Nikolenko, GN Delviks-Frankenberry, KA Jere, A Pathak, VK AF Nikolenko, G. N. Delviks-Frankenberry, K. A. Jere, A. Pathak, V. K. TI Mutations in the reverse transcriptase connection and RNase H domains exhibit dual resistance to nucleoside and non-nucleoside reverse transcriptase inhibitors SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Nikolenko, G. N.; Delviks-Frankenberry, K. A.; Jere, A.; Pathak, V. K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA. RI Delviks-Frankenberry, Krista/M-4822-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A55 EP A55 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100068 ER PT J AU Nissley, DV Shenk, JL Ambrose, Z Strathern, JN Sluis-Cremer, N AF Nissley, D. V. Shenk, J. L. Ambrose, Z. Strathern, J. N. Sluis-Cremer, N. TI The fidelity of HIV-1 reverse transcription: reverse transcriptase variants with altered mutation levels during replication SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Nissley, D. V.] NCI, SAIC Frederick Inc, BRP, Frederick, MD 21701 USA. [Nissley, D. V.; Shenk, J. L.; Strathern, J. N.] NCI, GRCBL, Frederick, MD 21701 USA. [Nissley, D. V.; Shenk, J. L.; Strathern, J. N.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A61 EP A61 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100074 ER PT J AU Palmer, S Maldarelli, F Kearney, M Shao, W Rock, D Mellors, J Albert, J Coffin, J AF Palmer, S. Maldarelli, F. Kearney, M. Shao, W. Rock, D. Mellors, J. Albert, J. Coffin, J. TI Single cell analysis of HIV DNA from infected patients SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Palmer, S.; Albert, J.] Karolinska Inst, Swedish Inst Infect Dis Control, Dept Virol, Solna, Sweden. [Palmer, S.; Maldarelli, F.; Kearney, M.; Shao, W.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Rock, D.] NIAID, CCMD Clin, Bethesda, MD 20892 USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Coffin, J.] Tufts Univ, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A75 EP A75 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100086 ER PT J AU Salzwedel, K Reddick, M Matalland, C Finnegan, C Adamson, C Sakalian, M Stanley, D Martin, D McCallister, S Freed, E Allaway, G AF Salzwedel, K. Reddick, M. Matalland, C. Finnegan, C. Adamson, C. Sakalian, M. Stanley, D. Martin, D. McCallister, S. Freed, E. Allaway, G. TI Role of Gag polymorphisms in HIV-1 sensitivity to the maturation inhibitor bevirimat SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Salzwedel, K.; Reddick, M.; Matalland, C.; Finnegan, C.; Sakalian, M.; Stanley, D.; Martin, D.; McCallister, S.; Allaway, G.] Panacos Pharmaceut, Gaithersburg, MD USA. [Adamson, C.; Freed, E.] Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A31 EP A31 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100047 ER PT J AU Vu, B Boyer, PL Siddiqui, MA Ambrose, Z Marquez, V Hughes, SH AF Vu, B. C. Boyer, P. L. Siddiqui, M. A. Ambrose, Z. Marquez, V. E. Hughes, S. H. TI Nucleoside analogues targeted against nucleoside reverse transcriptase inhibitor-resistant HIV-1 reverse transcriptase SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 17th International HIV Drug Resistance Workshop CY JUN 10-14, 2008 CL Sitges, SPAIN C1 [Vu, B. C.; Hughes, S. H.] NCI Frederick, HIV Drug Resistance Program, Frederick, MD USA. [Siddiqui, M. A.; Hughes, S. H.] NCI Frederick, Med Chem Lab, Frederick, MD USA. [Ambrose, Z.] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2008 VL 13 IS 4 BP A37 EP A37 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 323EY UT WOS:000257428100053 ER PT J AU Hallak, M Vazana, L Shpilberg, O Levy, I Mazar, J Nathan, I AF Hallak, Maher Vazana, Liat Shpilberg, Ofer Levy, Itai Mazar, Julia Nathan, Ilana TI A molecular mechanism for mimosine-induced apoptosis involving oxidative stress and mitochondrial activation SO APOPTOSIS LA English DT Article DE apoptosis; mimosine; mitochondria; reactive oxygen species ID PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; DNA-REPLICATION; REACTIVE OXYGEN; CELL-DEATH; NONSTEROIDAL ANTIESTROGENS; PROTEIN; CYCLE; COMPLEX; ARREST AB Mimosine, a non-protein amino acid, is mainly known for its action as a reversible inhibitor of DNA replication and, therefore, has been widely used as a cell cycle synchronizing agent. Recently, it has been shown that mimosine also induces apoptosis, as mainly reflected in its ability to elicit characteristic nuclear changes. The present study elucidates the mechanism underlying mimosine's apoptotic effects, using the U-937 leukemia cell line. We now demonstrate that in isolated rat liver mitochondria, mimosine induces mitochondrial swelling that can be inhibited by cyclosporine A, indicative of permeability transition (PT) mega-channel opening. Mimosine-induced apoptosis was accompanied by formation of hydrogen peroxide and a decrease in reduced glutathione levels. The apoptotic process was partially inhibited by cyclosporine A and substantially blocked by the antioxidant N-acetylcysteine, suggesting an essential role for reactive oxygen species formation during the apoptotic processes. The apoptosis induced by mimosine was also accompanied by a decrease in mitochondrial membrane potential, cytochrome c release and caspase 3 and 9 activation. Our results thus imply that mimosine activates apoptosis through mitochondrial activation and formation of H2O2, both of which play functional roles in the induction of cell death. C1 [Hallak, Maher; Vazana, Liat; Nathan, Ilana] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem, IL-84101 Beer Sheva, Israel. [Hallak, Maher; Vazana, Liat; Levy, Itai; Nathan, Ilana] Soroka Univ Med Ctr, Inst Hematol, IL-84883 Beer Sheva, Israel. [Shpilberg, Ofer] Rabin Med Ctr, Inst Hematol, Petah Tiqwa, Israel. [Mazar, Julia] NIH, Bethesda, MD 20892 USA. RP Nathan, I (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem, IL-84101 Beer Sheva, Israel. EM nathan@bgu.ac.il NR 36 TC 22 Z9 25 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JAN PY 2008 VL 13 IS 1 BP 147 EP 155 DI 10.1007/s10495-007-0156-7 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 250IM UT WOS:000252293200013 PM 18058236 ER PT S AU Gates, MB Tomer, KB Deterding, LJ AF Gates, Matthew B. Tomer, Kenneth B. Deterding, Leesa J. BE Popescu, C Zamfir, AD Dinca, N TI MALDI/MS COMPARISON OF FE-NTA IMMOBILIZED METAL AFFINITY CHROMATOGRAPUY AND COMMERCIALLY-AVAILABLE METAL OXIDE AFFINITY RESINS FOR PHOSPHOPEPTIDE ENRICHMENT SO APPLICATIONS OF MASS SPECTROMETRY IN LIFE SAFETY SE NATO Science for Peace and Security Series A-Chemistry and Biology LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Applications of Mass Spectrometry in Life Safety CY SEP 24-27, 2007 CL Arad, ROMANIA SP NATO ID DESORPTION/IONIZATION MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; PHOSPHOPROTEOME ANALYSIS; PHOSPHORYLATED PEPTIDES; AQUEOUS-SOLUTIONS; ADSORPTION; ZIRCONIA; TIO2; PROTEIN; SITE AB Immobilized metal ion affinity chromatography in combination with mass spectrometry has been used to determine the extent of phosphorylation and the specific sites of phosphorylation on proteins. There are several advantages to this combined approach. Immobilized metal ion affinity chromatography is the use of resins with metal constituents and metal oxides to enrich and isolate phosphopeptides. By selectively enriching phosphopeptides on media prior to MS analyses, suppression effects can be greatly reduced. In this report, we have investigated several resins from various sources to assess the phosphopeptide enrichment capabilities of each prior to mass spectrometric analyses. The phosphopeptide enrichment capabilities of six different resins, Glygen TiO2, ZrO2, and mixed ZrO2 and TiO2 NuTips, Titansphere TiO2 resin, PhosTrap magnetic titanium beads, and a Fe-NTA resin, are compared. C1 [Gates, Matthew B.; Tomer, Kenneth B.; Deterding, Leesa J.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Gates, MB (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. NR 39 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-4641 BN 978-1-4020-8809-4 J9 NATO SCIE PEACE SECU PY 2008 BP 37 EP 54 DI 10.1007/978-1-4020-8811-7_3 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIJ27 UT WOS:000259998700003 ER PT S AU Perdevara, I Iacob, RE Przybylski, M Tomer, KB AF Perdevara, Irina Iacob, Roxana Elena Przybylski, Michael Tomer, Kenneth B. BE Popescu, C Zamfir, AD Dinca, N TI SITE SPECIFIC IDENTIFICATION OF N-LINKED GLYCOSYLATION IN PROTEINS BY LIQUID CHROMATOGRAPHY-ELECTROSPRAY IONIZATION TANDEM MASS SPECTROMETRY SO APPLICATIONS OF MASS SPECTROMETRY IN LIFE SAFETY SE NATO Science for Peace and Security Series A-Chemistry and Biology LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Applications of Mass Spectrometry in Life Safety CY SEP 24-27, 2007 CL Arad, ROMANIA SP NATO ID MS MS; VIRUS; OLIGOSACCHARIDES; FRAGMENTATION; GLYCOPEPTIDES AB Recently, we reported the characterization of the glycans attached at the 11 N-glycosylation sites of Hepatitis C virus E2 envelope glycoprotein by tandem mass spectrometry. Infections caused by Hepatitis C virus represent the main cause of liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma. The N-linked sugars consist primarily of high mannose glycans, with structures ranging from the minimal core structure, Man(3)GlcNAC(2) (Man3) up to 12 hexose residues attached to the GlcNAc-beta(1-4)-GlcNAc core (depicted as Hex(3)Man(9)GlcNAc(2)). Furthermore. the site N41 (N423) was observed to contain complex type glycans with the structures Man3-GlcNAc and Man3-GlcNAcFuc, in addition to the high mannose population Man3 through Man6, while the site N48 (N430) was occupied exclusively with complex type glycans (Man3-Fuc, Man3-GlcNAcFuc and Man3-GlcNAc(2)Fuc). The present contribution summarizes our experimental observations upon the factors which may have an impact on the CID tandem mass spectra of glycopeptides. C1 [Perdevara, Irina; Przybylski, Michael] Univ Konstanz, Analyt Chem Lab, D-7750 Constance, Germany. [Perdevara, Irina; Iacob, Roxana Elena; Tomer, Kenneth B.] NIEHS, NIH, Struct Biol Lab, Mass Spectrometry Grp, Res Triangle Pk, NC 27709 USA. [Iacob, Roxana Elena] Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. RP Perdevara, I (reprint author), Univ Konstanz, Analyt Chem Lab, D-7750 Constance, Germany. NR 23 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1874-6489 BN 978-1-4020-8809-4 J9 NATO SCI PEACE SEC A JI NATO Sci. Peace Secur. Ser. A-Chem. Biol. PY 2008 BP 109 EP + DI 10.1007/978-1-4020-8811-7_8 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIJ27 UT WOS:000259998700008 ER PT S AU Williams, JG Deterding, LJ Tommer, KB AF Williams, Jason G. Deterding, Leesa J. Tommer, Kenneth B. BE Popescu, C Zamfir, AD Dinca, N TI CHARACTERIZATION OF IMMUNE RESPONSES TO PATHOGEN CHALLENGE BY MS-BASED EPITOPE MAPPING SO APPLICATIONS OF MASS SPECTROMETRY IN LIFE SAFETY SE NATO Science for Peace and Security Series A-Chemistry and Biology LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Applications of Mass Spectrometry in Life Safety CY SEP 24-27, 2007 CL Arad, ROMANIA SP NATO ID IMMUNODEFICIENCY-VIRUS TYPE-1; IONIZATION MASS-SPECTROMETRY; ANTIBODY 4E10 RECOGNIZES; MONOCLONAL-ANTIBODY; CHEMICAL-MODIFICATION; GP41 EPITOPE; LIMITED PROTEOLYSIS; PROTEIN; GLYCOPROTEIN; COMPLEX AB Mass spectrometry has long proven to be an outstanding bioanalytical technique for identifying proteins, defining their amino acid sequences, and for identifying sites of protein modifications. The application of mass spectrometry to more complicated biological structures. however, is less well established. We have been applying mass spectrometry to structural studies protein, especially to the determination of epitopes on proteins from pathogens that are recognized by monoclonal antibodies as part of the body's immune system. As part of the defense mechanism against the invading pathogens, the body produces a cadre of antibodies to various epitopes on the pathogens. Here, we outline the development of epitope mapping techniques by mass spectrometry for the identification of linear epitopes and complex discontinuous epitopes using examples from our studies of epitopes on HIV proteins. C1 [Williams, Jason G.; Deterding, Leesa J.; Tommer, Kenneth B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Mass Spectrometry Grp, NIH, Res Triangle Pk, NC USA. RP Williams, JG (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, Mass Spectrometry Grp, NIH, Res Triangle Pk, NC USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-4641 BN 978-1-4020-8809-4 J9 NATO SCIE PEACE SECU PY 2008 BP 123 EP 137 DI 10.1007/978-1-4020-8811-7_9 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIJ27 UT WOS:000259998700009 ER PT S AU Deterding, LJ Tomer, KB AF Deterding, Leesa J. Tomer, Kenneth B. BE Popescu, C Zamfir, AD Dinca, N TI CHEMICAL SURFACE MODIFICATION AND CHEMICAL CROSSLINKING COMBINED WITH MASS SPECTROMETRY FOR PROTEIN TERTIARY STRUCTURAL INFORMATION SO APPLICATIONS OF MASS SPECTROMETRY IN LIFE SAFETY SE NATO Science for Peace and Security Series A-Chemistry and Biology LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Applications of Mass Spectrometry in Life Safety CY SEP 24-27, 2007 CL Arad, ROMANIA SP NATO ID SJOGRENS-SYNDROME; GENOMICS; SPECTROSCOPY; PROPIONATE); TOPOLOGY; NMR AB In an effort to gain tertiary structural information of proteins, chemical modification of surface exposed residues and chemical crosslinking have been used in combination with mass spectrometry. For this work, the acetylation of lysine residues was used as a chemical modification reagent. The lysine residues that are determined to be acetylated are, thus, assumed to be surface accessible. The chemical crosslinker DTSSP, 3,3'-dithiobis-[sulfosuccinimidylpropionate], was used for the crosslinking experiments. DTSSP is a homobifunctional amine reactive crosslinker that is cleavable. Therefore, an aliquot of the crosslinked protein was then subjected to conditions that would result in cleavage of the linker. After performing all modification and crosslinking experiments, the protein was digested and analyzed by both MALDI and LC/ESI mass spectrometry. For proof-of-principle, bovine beta-lactoglobulin was used for these analyses, and the results are compared to the X-ray crystal structure of the protein. As an extension of this work, these biochemical and mass spectrometric techniques have been applied to a protein of unknown structure. C1 [Deterding, Leesa J.; Tomer, Kenneth B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Deterding, LJ (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. NR 19 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1874-6489 BN 978-1-4020-8809-4 J9 NATO SCI PEACE SEC A JI NATO Sci. Peace Secur. Ser. A-Chem. Biol. PY 2008 BP 139 EP 150 DI 10.1007/978-1-4020-8811-7_10 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIJ27 UT WOS:000259998700010 ER PT J AU Emmert-Streib, F Arabnia, HR Yang, MQ AF Emmert-Streib, Frank Arabnia, Hamid R. Yang, Mary Qu TI Preface SO APPLIED ARTIFICIAL INTELLIGENCE LA English DT Editorial Material C1 [Emmert-Streib, Frank] Univ Washington, Dept Biostat & Genome Sci, Seattle, WA 98195 USA. [Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Grad Studies Res Ctr, Athens, GA 30602 USA. [Yang, Mary Qu] NHGRI, NIH, Bethesda, MD 20892 USA. RP Emmert-Streib, F (reprint author), Queens Univ Belfast, Ctr Canc Res & Cell Biol, 97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland. RI Emmert-Streib, Frank/G-8099-2011 OI Emmert-Streib, Frank/0000-0003-0745-5641 NR 0 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0883-9514 J9 APPL ARTIF INTELL JI Appl. Artif. Intell. PY 2008 VL 22 IS 7-8 BP 617 EP 618 DI 10.1080/08839510802164051 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 344DC UT WOS:000258905000001 ER PT J AU Shamir, L Nemiroff, RJ AF Shamir, Lior Nemiroff, Robert J. TI Astronomical pipeline processing using fuzzy logic SO APPLIED SOFT COMPUTING LA English DT Article DE fuzzy logic; astronomy; astronomical pipelines ID COSMIC-RAY REJECTION; SURVEY TELESCOPE; SINGLE IMAGES; IDENTIFICATION; HITS; SKY AB Fundamental astronomical questions on the composition of the universe, the abundance of Earth-like planets, and the cause of the brightest explosions in the universe are being attacked by robotic telescopes costing billions of dollars and returning vast pipelines of data. The success of these programs depends on the accuracy of automated real time processing of images never seen by a human, and all predicated on fast and accurate automatic identifications of known astronomical objects and new astronomical transients. In this paper the needs of modern astronomical pipelines are discussed in the light of fuzzy-logic based decision-making. Several specific fuzzy-logic algorithms have been develop for the first time for astronomical purposes, and tested with excellent results on a test pipeline of data from the existing Night Sky Live sky survey. (c) 2006 Elsevier B.V. All rights reserved. C1 NIA, NIH, Genet Lab, Image Anal Grp, Baltimore, MD 21224 USA. Michigan Technol Univ, Dept Phys, Houghton, MI 49931 USA. RP Shamir, L (reprint author), NIA, NIH, Genet Lab, Image Anal Grp, 333 Cassell Dr, Baltimore, MD 21224 USA. EM shamirl@mail.nih.gov NR 26 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-4946 EI 1872-9681 J9 APPL SOFT COMPUT JI Appl. Soft. Comput. PD JAN PY 2008 VL 8 IS 1 BP 79 EP 87 DI 10.1016/j.asoc.2006.10.013 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Computer Science GA 211FA UT WOS:000249508500006 ER PT J AU Cannon, TD Cadenhead, K Cornblatt, B Woods, SW Addington, J Walker, E Seidman, LJ Perkins, D Tsuang, M McGlashan, T Heinssen, R AF Cannon, Tyrone D. Cadenhead, Kristin Cornblatt, Barbara Woods, Scott W. Addington, Jean Walker, Elaine Seidman, Larry J. Perkins, Diana Tsuang, Ming McGlashan, Thomas Heinssen, Robert TI Prediction of psychosis in youth at high clinical risk SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ULTRA-HIGH-RISK; RANDOMIZED CONTROLLED-TRIAL; EDINBURGH HIGH-RISK; PRODROMAL SCHIZOPHRENIA; YOUNG-PEOPLE; INTERRATER RELIABILITY; PROSPECTIVE COHORT; SCHIZOTYPY; DISORDERS; VALIDITY AB Context: Early detection and prospective evaluation of individuals who will develop schizophrenia or other psychotic disorders are critical to efforts to isolate mechanisms underlying psychosis onset and to the testing of preventive interventions, but existing risk prediction approaches have achieved only modest predictive accuracy. Objectives: To determine the risk of conversion to psychosis and to evaluate a set of prediction algorithms maximizing positive predictive power in a clinical high-risk sample. Design, Setting, and Participants: Longitudinal study with a 2 1/2-year follow-up of 291 prospectively identified treatment-seeking patients meeting Structured Interview for Prodromal Syndromes criteria. The patients were recruited and underwent evaluation across 8 clinical research centers as part of the North American Prodrome Longitudinal Study. Main Outcome Measure: Time to conversion to a fully psychotic form of mental illness. Results: The risk of conversion to psychosis was 35%, with a decelerating rate of transition during the 2 1/2year follow-up. Five features assessed at baseline contributed uniquely to the prediction of psychosis: a genetic risk for schizophrenia with recent deterioration in functioning, higher levels of unusual thought content, higher levels of suspicion/paranoia, greater social impairment, and a history of substance abuse. Prediction algorithms combining 2 or 3 of these variables resulted in dramatic increases in positive predictive power (ie, 68%, 80%) compared with the prodromal criteria alone. Conclusions: These findings demonstrate that prospective ascertainment of individuals at risk for psychosis is feasible, with a level of predictive accuracy comparable to that in other areas of preventive medicine. They provide a benchmark for the rate and shape of the psychosis risk function against which standardized preventive intervention programs can be compared. C1 [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Cadenhead, Kristin; Tsuang, Ming] Univ Calif San Diego, Dept Psychiat, San Diego, CA USA. [Cornblatt, Barbara] Zucker Hillside Hosp, Long Isl City, NY USA. [Woods, Scott W.; McGlashan, Thomas] Yale Univ, New Haven, CT USA. [Addington, Jean] Univ Toronto, Toronto, ON, Canada. [Seidman, Larry J.; Tsuang, Ming] Harvard Univ, Sch Med, Boston, MA USA. [Perkins, Diana] Univ N Carolina, Chapel Hill, NC USA. [Walker, Elaine] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Heinssen, Robert] NIMH, Div Adult Translat Res, Schizophrenia Spectrum Disorders Res Program, Bethesda, MD 20892 USA. RP Cannon, TD (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall, Los Angeles, CA 90095 USA. EM cannon@psych.ucla.edu FU NCATS NIH HHS [UL1 TR000454]; NIMH NIH HHS [K23 MH001905, K24 MH076191, K24 MH076191-01A1, K24 MH076191-02, K24 MH076191-03, K24 MH076191-04, R01 MH060720, R01 MH060720-01A1, R01 MH060720-02, R01 MH060720-03, R01 MH060720-04, R01 MH060720-05, R01 MH060720-06A1, R01 MH060720-07, R01 MH060720-08, R01 MH060720-09, U01 MH081944, U01 MH081944-01A1] NR 64 TC 687 Z9 704 U1 10 U2 60 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2008 VL 65 IS 1 BP 28 EP 37 DI 10.1001/archgenpsychiatry.2007.3 PG 10 WC Psychiatry SC Psychiatry GA 248ST UT WOS:000252176400005 PM 18180426 ER PT J AU Merikangas, KR Herrell, R Swendsen, J Rossler, W Ajdacic-Gross, V Angst, J AF Merikangas, Kathleen R. Herrell, Richard Swendsen, Joel Roessler, Wulf Ajdacic-Gross, Vladeta Angst, Jules TI Specificity of bipolar spectrum conditions in the Comorbidity of mood and substance use disorders SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE DISORDERS; SEVERE MENTAL-ILLNESS; ANXIETY DISORDERS; PSYCHIATRIC-DISORDERS; COMMUNITY SAMPLE; II DISORDER; DRUG-ABUSE; PREVALENCE AB Context: Although an association between mood disorders and substance use disorders has been well established, there is a lack of long-term prospective data on the order of onset and subtypes of mood disorders associated with specific substances and their progression. Objective: To estimate the respective risks posed by subtypes of mood disorders or bipolar spectrum conditions for the subsequent development of substance use disorders. Design: Six waves of direct diagnostic interviews were administered to a sample of young adults during a 20-year period. Mood disorders and syndromes assessed at each interview were used to predict the cumulative incidences of substance use disorders at subsequent interview waves. Participants: We followed up 591 individuals (292 men and 299 women) who were selected at study enrollment from a representative sample of young adults in Zurich, Switzerland. Main Outcome Measures: Structured Diagnostic Interview for Psychopathologic and Somatic Syndromes, a semistructured clinical interview that collected data on the spectrum of expression of mood disorders and substance use and disorders for DSM-III-R and DSM-IV criteria. Results: Individuals having manic symptoms were at significantly greater risk for the later onset of alcohol abuse/dependence, cannabis use and abuse/dependence, and benzodiazepine use and abuse/dependence. Bipolar II disorder predicted both alcohol abuse/dependence and benzodiazepine use and abuse/dependence. In contrast, major depression was predictive only of later benzodiazepine abuse/dependence. Conclusions: In comparison with major depression, bipolar II disorder was associated with the development of alcohol and benzodiazepine use and disorders. There was less specificity of manic symptoms that tended to predict all levels of the substances investigated herein. The different patterns of association between mood disorders and substance use trajectories have important implications for prevention and provide lacking information about underlying mechanisms. C1 [Merikangas, Kathleen R.; Herrell, Richard] NIH, NIMH, Intramural Res Program, Sect Dev Genet Epidemiol,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Swendsen, Joel] Univ Bordeaux, Natl Sci Res Ctr, Bordeaux, France. [Roessler, Wulf; Ajdacic-Gross, Vladeta; Angst, Jules] Univ Psychiat Hosp, Zurich, Switzerland. RP Merikangas, KR (reprint author), NIH, NIMH, Intramural Res Program, Sect Dev Genet Epidemiol,Dept Hlth & Human Serv, 1A201 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM kathleen.merikangas@nih.gov OI Ajdacic-Gross, Vladeta/0000-0002-7032-9237 NR 57 TC 97 Z9 98 U1 3 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2008 VL 65 IS 1 BP 47 EP 52 DI 10.1001/archgenpsychiatry.2007.18 PG 6 WC Psychiatry SC Psychiatry GA 248ST UT WOS:000252176400007 PM 18180428 ER PT J AU Irie, F Fitzpatrick, AL Lopez, OL Kuller, LH Peila, R Newman, AB Launer, LJ AF Irie, Fumiko Fitzpatrick, Annette L. Lopez, Oscar L. Kuller, Lewis H. Peila, Rita Newman, Anne B. Launer, Lenore J. TI Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon 4 SO ARCHIVES OF NEUROLOGY LA English DT Article ID MIDLIFE BLOOD-PRESSURE; GLYCATION END-PRODUCTS; CARDIOVASCULAR HEALTH; APOLIPOPROTEIN-E; VASCULAR DEMENTIA; COGNITIVE DECLINE; MELLITUS; BRAIN; DIAGNOSIS; CLASSIFICATION AB Background: Diabetes and the.apolipoprotein E epsilon 4 allele (APOE epsilon 4) increase the risk for Alzheimer disease (AD). We hypothesize that APOE epsilon 4 may modify the risk for AD in individuals with diabetes. Objective: To examine the joint effect of type 2 diabetes and APOE epsilon 4 on the risk of AD, AD with vascular dementia (mixed AD), and vascular dementia without AD. Design: The Cardiovascular Health Study (CHS) Cognition Study (1992-2000) is a prospective study designed to identify all existing and new cases of dementia among study participants. Diagnoses were made according to international criteria for dementia and subtypes. There were 2547 dementia-free participants in the CHS Cognition Study cohort with complete information on APOE epsilon 4 and type 2 diabetes status; among these, 411 new cases of dementia developed. Risk of dementia was estimated with a Cox proportional hazard model adjusted for age and other demographic and cardiovascular risk factors. Results: Compared with those who had neither type 2 diabetes nor APOE epsilon 4, those with both factors had a significantly higher risk of AD (hazard ratio, 4.58; 95% confidence interval, 2.18-9.65) and mixed AD (hazard ratio, 3.89; 95% confidence interval, 1.46-10.40). Conclusion: These data suggest that having both diabetes and APOE epsilon 4 increases the risk of dementia, especially for AD and mixed AD. C1 [Irie, Fumiko; Peila, Rita; Launer, Lenore J.] NIA, Neuroepidemiol Sect, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Kuller, Lewis H.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Launer, LJ (reprint author), NIA, Neuroepidemiol Sect, Lab Epidemiol Demog & Biometry, NIH, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU Intramural NIH HHS; NHLBI NIH HHS [N01-HC-85079, N01-HC-85086]; NIA NIH HHS [5R01 AG15928-02] NR 35 TC 146 Z9 154 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2008 VL 65 IS 1 BP 89 EP 93 DI 10.1001/archneurol.2007.29 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 250PR UT WOS:000252313000011 PM 18195144 ER PT J AU Ferraris, S Clark, S Garelli, E Davidzon, G Moore, SA Kardon, RH Bienstock, RJ Longley, MJ Mancuso, M Rios, PG Hirano, M Copeland, WC DiMauro, S AF Ferraris, Silvio Clark, Susanna Garelli, Emanuela Davidzon, Guido Moore, Steven A. Kardon, Randy H. Bienstock, Rachelle J. Longley, Matthew J. Mancuso, Michelangelo Rios, Purificacion Gutierrez Hirano, Michio Copeland, William C. DiMauro, Salvatore TI Progressive external ophthalmoplegia and vision and hearing loss in a patient with mutations in POLG2 and OPA1 SO ARCHIVES OF NEUROLOGY LA English DT Article ID DNA-POLYMERASE-GAMMA; BASE EXCISION-REPAIR; ACCESSORY SUBUNIT; AUTOSOMAL-DOMINANT; DELETIONS; IDENTIFICATION; BINDING AB objective: To describe the clinical features, muscle pathological characteristics, and molecular studies of a patient with a mutation in the gene encoding the accessory subunit (p55) of polymerase gamma (POLG2) and a mutation in the OPAL gene. Design: Clinical examination and morphological., biochemical, and molecular analyses. Setting: Tertiary care university hospitals and molecular genetics and scientific computing laboratory. Patient: A 42-year-old man experienced hearing loss, progressive external ophthalmoplegia (PEO), loss of central vision, macrocytic anemia, and hypogonadism. His family history was negative for neurological disease, and his serum lactate level was normal. Results: A muscle biopsy specimen showed scattered intensely succinate dehydrogenase-positive and cytochrome-c oxidase-negative fibers. Southern blot of muscle mitochondrial DNA showed multiple deletions. The results of screening for mutations in the nuclear genes associated with PEO and multiple mitochondrial DNA deletions, including those in POLG (polymerase gamma gene), ANTI (gene. encoding adenine nucleotide translocator 1), and PEO1, were negative, but sequencing of POLG2 revealed a G1247C mutation in exon 7, resulting in the substitution of a highly conserved glycine with an alanine at codon 416 (G416A). Because biochemical analysis of the mutant protein showed no alteration in chromatographic properties and normal ability to protect the catalytic subunit from N-ethylmaleimide, we also sequenced the OPAL gene and identified a novel heterozygous mutation (Y582C). Conclusion: Although we initially focused on the mutation in POLG2, the mutation in OPAL is more likely to explain the late-onset PEO and multisystem disorder in this patient. C1 [Davidzon, Guido; Rios, Purificacion Gutierrez; Hirano, Michio; DiMauro, Salvatore] Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10032 USA. [Ferraris, Silvio; Garelli, Emanuela] Univ Turin, Dept Pediat, I-10124 Turin, Italy. [Clark, Susanna; Bienstock, Rachelle J.; Longley, Matthew J.; Copeland, William C.] Natl Inst Environm Hlth Sci, Lab Mol Genet & Sci Comp Lab, NIH, Res Triangle Pk, NC USA. [Moore, Steven A.] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. [Kardon, Randy H.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [Mancuso, Michelangelo] Univ Pisa, Dept Neurosci, Neurol Inst, Pisa, Italy. RP DiMauro, S (reprint author), Columbia Univ, Dept Neurol, Med Ctr, 1150 St Nicholas Ave,Room 313, New York, NY 10032 USA. EM sd12@columbia.edu RI Gutierrez Rios, Purificacion/I-4234-2015 OI Gutierrez Rios, Purificacion/0000-0002-4585-1912 FU Intramural NIH HHS [Z01 ES065078-14]; NICHD NIH HHS [P01 HD032062, HD32062]; NINDS NIH HHS [NS11766, P01 NS011766] NR 23 TC 31 Z9 33 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2008 VL 65 IS 1 BP 125 EP 131 DI 10.1001/archneurol.2007.9 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 250PR UT WOS:000252313000017 PM 18195150 ER PT J AU Wendler, D Jenkins, T AF Wendler, David Jenkins, Tammara TI Children's and their parents' views on facing research risks for the benefit of others SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; 2 CORRELATED PROPORTIONS; INFORMED-CONSENT; CLINICAL-RESEARCH; MINIMAL RISK; PARTICIPATION; ATTITUDES; STANDARD; ASSENT; PERSPECTIVES AB Objective: To assess children's and parents' attitudes regarding pediatric research that poses minimal risk or a minor increase over minimal risk and does not offer the potential to benefit the child clinically. Design: Separate in-person interviews with children and their parents. Setting: Clinics where the children were receiving clinical care or participating in clinical research for asthma or cancer. Participants: Children aged 7 to 14 years and their parents or legal guardians. Intervention: In-person interviews. Main Outcome Measures: Respondents' willingness to enroll the child in nonbeneficial research and charitable activities that posed the same risks. Results: Overall, 81 child-parent pairs were interviewed. For a hypothetical study that would not benefit the child and posed a risk of headache, 71% of the children were willing to participate, and 72% of the parents would allow their children to participate. For a hypothetical study that would not benefit the child and posed a very small chance of a broken leg, 43% of the children and 24% of the parents endorsed the child's participation. Overall, respondents were equally willing to have the child help others by participating in nonbeneficial research or by participating in a charitable activity. Conclusions: Most respondents were willing to have the child participate in some nonbeneficial research, and most did not consider nonbeneficial pediatric research to be more problematic than charitable activities for children. These findings provide empirical data to support the acceptability of exposing children to some research risks for the benefit of others. C1 [Wendler, David] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Jenkins, Tammara] NICHHD, Natl Ctr Med Rehabil Res, Pediat Crit Care & Rehabil Res Program, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 38 TC 29 Z9 32 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JAN PY 2008 VL 162 IS 1 BP 9 EP 14 DI 10.1001/archpediatrics.2007.3 PG 6 WC Pediatrics SC Pediatrics GA 248SQ UT WOS:000252176100002 PM 18180406 ER PT J AU Shah, JP Danoff, JV Desai, MJ Parikh, S Nakamura, LY Phillips, TM Gerber, LH AF Shah, Jay P. Danoff, Jerome V. Desai, Mehul J. Parikh, Sagar Nakamura, Lynn Y. Phillips, Terry M. Gerber, Lynn H. TI Mochemicals associated with pain and inflammation are elevated in sites near to and remote from active myofascial trigger points SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE inflammation; microdialysis; myofascial pain; rehabilitation; trigger points; myofascial ID IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS; MUSCULOSKELETAL PAIN; CYTOKINES; MUSCLE; HYPERALGESIA; INJECTION AB Objectives: To investigate the biochemical milieu of the upper trapezius muscle in subjects with active, latent, or absent myofascial trigger points (MTPs) and to contrast this with that of the noninvolved gastrocnemius muscle. Design: We used a microanalytic technique, including needle insertions at standardized locations in subjects identified as active (having neck pain and MTP), latent (no neck pain but with MTP), or normal (no neck pain, no MTP). We followed a predetermined sampling schedule; first in the trapezius muscle and then in normal gastrocnemius muscle, to measure pH, bradykinin, substance P, calcitonin gene-related peptide, tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), IL-6, IL-8, serotonin, and norepinephrine, using immunocapillary electrophoresis and capillary electrochromatography. Pressure algometry was obtained. We compared analyte concentrations among groups with 2-way repeated-measures analysis of variance. Setting: A biomedical research facility. Participants: Nine healthy volunteer subjects. Interventions: Not applicable. Main Outcome Measures: Preselected analyte concentrations. Results: Within the trapezius muscle, concentrations for all analytes were higher in active subjects than in latent or normal subjects (P<.002); pH was lower (P<.03). At needle insertion, analyte concentrations in the trapezius for the active group were always higher (pH not different) than concentrations in the gastrocnemius muscle. At all times within the gastrocnemius, the active group had higher concentrations of all analytes than did subjects in the latent and normal groups (P<.05); pH was lower (P<.01). Conclusions: We have shown the feasibility of continuous, in vivo recovery of small molecules from soft tissue without harmful effects. Subjects with active MTPs in the trapezius muscle have a biochemical milieu of selected inflammatory mediators, neuropeptides, cytokines, and catecholamines different from subjects with latent or absent MTPs in their trapezius. These concentrations also differ quantitatively from a remote, uninvolved site in the gastrocnemius muscle. The milieu of the gastrocnemius in subjects with active MTPs in the trapezius differs from subjects without active MTPs. C1 [Shah, Jay P.; Danoff, Jerome V.; Parikh, Sagar] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. [Danoff, Jerome V.] George Washington Univ, Dept Exercise Sci, Washington, DC USA. [Desai, Mehul J.] George Washington Univ, Dept Anesthesiol & Crit Care Med, Washington, DC USA. [Nakamura, Lynn Y.] Natl Rehabil Hosp, Washington, DC USA. [Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, NIH, Ultramicro Analyt Immunochem Resource, Bethesda, MD USA. [Gerber, Lynn H.] George Mason Univ, Ctr Study Chron Illness & Disabil, Coll Hlth & Human Serv, Fairfax, VA 22030 USA. RP Shah, JP (reprint author), NIH, Dept Rehabil Med, Clin Res Ctr, 10 Ctr Dr,Rm 1-1469,MSC 1604, Bethesda, MD 20892 USA. EM jshah@mail.cc.nih.gov FU Intramural NIH HHS NR 21 TC 202 Z9 208 U1 0 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2008 VL 89 IS 1 BP 16 EP 23 DI 10.1016/j.apmr.2007.10.018 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 249LB UT WOS:000252228600004 PM 18164325 ER PT J AU Chan, PC Hills, GD Kissling, GE Nyska, A AF Chan, P. C. Hills, G. D. Kissling, G. E. Nyska, A. TI Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice SO ARCHIVES OF TOXICOLOGY LA English DT Article DE 4-methylimidazole; toxicity; carcinogenicity; rats; mice ID OLFACTORY MUCOSA; DISPOSITION; METHIMAZOLE; CATTLE; TESTS AB 4-Methylimidazole (4MI) is used in the manufacture of pharmaceuticals, photographic chemicals, dyes and pigments, cleaning and agricultural chemicals, and rubber. It has been identified as a by-product of fermentation in foods and has been detected in mainstream and side stream tobacco smoke. 4MI was studied because of its high potential for human exposure. Groups of 50 male and 50 female F344/N rats were fed diets containing 0-, 625-, 1,250-, or 2,500 ppm 4MI (males) or 0-, 1,250-, 2,500-, or 5,000 ppm 4MI (females) for 106 weeks. Based on the food consumption the calculated average daily doses were approximately 30, 55, or 115 mg 4MI/kg body weight to males and 60, 120, or 250 mg 4MI/kg to females. Survival of all exposed groups of males and females was similar to that of the control groups. The mean body weights of males in the 1,250- and 2,500 ppm groups and females in the 2,500- and 5,000 ppm groups were less than those of the control groups throughout the study. Feed consumption by 5,000 ppm females was less than that by the controls. Clonic seizures, excitability, hyperactivity, and impaired gait were observed primarily in 2,500- and 5,000 ppm females. The incidence of mononuclear cell leukemia in the 5,000 ppm females was significantly greater than that in the controls. The incidences of hepatic histiocytosis, chronic inflammation, and focal fatty change were significantly increased in all exposed groups of male and female rats. The incidences of hepatocellular eosinophilic and mixed cell foci were significantly increased in 2,500 ppm males and 5,000 ppm females. Groups of 50 male and 50 female B6C3F1 mice were fed diets containing 0-, 312-, 625-, or 1,250 ppm 4MI for 106 weeks. Based on the food consumption the calculated average daily doses were approximately 40, 80, or 170 mg 4MI/kg body weight to males and females. Survival of all exposed groups of males and females was similar to that of the control groups. Mean body weights of males and females in the 1,250 ppm groups and that in the 312- and 625 ppm females were less than those of the control groups. Feed consumption by exposed groups of male and female mice was similar to that by the controls. The incidences of alveolar/bronchiolar adenoma in all exposed groups of females, alveolar/bronchiolar carcinoma in 1,250 ppm males, and alveolar/bronchiolar adenoma or carcinoma (combined) in 1,250 ppm males and 625- and 1,250 ppm females were significantly greater than those in the control groups. The incidence of alveolar epithelial hyperplasia was significantly increased in the 1,250 ppm females. 4MI is carcinogenic inducing alveolar/bronchiolar adenoma and carcinoma in male and female mice. 4MI may also induce mononuclear cell leukemia in female rats. C1 [Chan, P. C.] NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. [Hills, G. D.] Integrated Syst Lab, Res Triangle Pk, NC 27709 USA. [Nyska, A.] Tel Aviv Univ, Timrat, Israel. [Kissling, G. E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Chan, PC (reprint author), NIEHS, Toxicol Operat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 37 TC 37 Z9 37 U1 8 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD JAN PY 2008 VL 82 IS 1 BP 45 EP 53 DI 10.1007/s00204-007-0222-5 PG 9 WC Toxicology SC Toxicology GA 253TB UT WOS:000252539400007 PM 17619857 ER PT B AU Misra, D Seamans, J Thoma, GR AF Misra, Dharitri Seamans, James Thoma, George R. BE Gschwind, R TI Testing the scalability of a DSpace-based archive SO ARCHIVING 2008, FINAL PROGRAM AND PROCEEDINGS LA English DT Proceedings Paper CT Archiving 2008 Conference 2008 CY JUN 24-27, 2008 CL Bern, SWITZERLAND SP Soc Imaging Sci & Tech, Amer Inst Conservat Hist Artist Works, Assoc Lib Collect & Tech Serv, Coalit Networked Informat, Digital Lib Federat, Digit Preservat Coalit, European Commiss Preservat & Access, Inter-Soc Color Coucil, Inst Phys, Museum Comp Network, Online Comp Lib Ctr, Royal Photog Soc AB The implementation of production-level large scale archives is often based on research prototypes that possess essential functions and characteristics, e.g., storage capacity, ingest, metadata recording, ability to migrate to newer formats, etc. However, a key characteristic that is often overlooked is scalability, i.e., the ability of the system to accommodate large numbers of items without compromising performance - while ingesting, indexing or access. Here we describe an investigation of archive scalability in a Java-based system (System for the Preservation of Electronic Resources or SPER) which was built by an R&D team at the U.S. National Library of Medicine to investigate various aspects of digital preservation. SPER uses DSpace as the underlying infrastructure for building and managing the digital archive. To confirm the capability of SPER/DSpace to serve as a large archive, we conducted scalability tests by generating and ingesting data for more than a million items, and studied ingest behavior as a,function of the archive size. This paper describes the test procedure and environment, the software developed to measure performance during ingest, and the characteristics of the ingested data. We present the ensuing results, which confirm the scalability of SPER/DSpace with acceptable ingest performance as the archive is expanded to a million items. C1 [Misra, Dharitri; Seamans, James; Thoma, George R.] US Natl Lib Med, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 1 U2 2 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 978-0-89208-277-3 PY 2008 BP 36 EP 40 PG 5 WC Art; Information Science & Library Science; Imaging Science & Photographic Technology SC Art; Information Science & Library Science; Imaging Science & Photographic Technology GA BHX95 UT WOS:000257314600008 ER PT J AU Cragg, G Bohlin, L AF Cragg, Gordon Bohlin, Lars TI Professor Torbjorn Norin A Tribute SO ARKIVOC LA English DT Biographical-Item C1 [Cragg, Gordon] NCI, NIH, Nat Prod Branch,Fairview Ctr, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA. [Bohlin, Lars] Uppsala Univ, Dept Med Chem, SE-75123 Uppsala, Sweden. RP Cragg, G (reprint author), NCI, NIH, Nat Prod Branch,Fairview Ctr, Dev Therapeut Program,Div Canc Treatment & Diag, Suite 206,POB B, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ARKAT USA INC PI GAINESVILLE PA C/O ALAN R KATRITZKY, UNIV FLORIDA, DEPT CHEMISTRY, PO BOX 117200, GAINESVILLE, FL 32611 USA SN 1424-6376 J9 ARKIVOC JI Arkivoc PY 2008 BP 1 EP 4 PN 6 PG 4 WC Chemistry, Organic SC Chemistry GA 365MF UT WOS:000260410000001 ER PT J AU Oyama, N Gona, P Salton, CJ Chuang, ML Jhaveri, RR Blease, SJ Manning, AR Lahiri, M Botnar, RM Levy, D Larson, MG O'Donnell, CJ Manning, WJ AF Oyama, Noriko Gona, Philimon Salton, Carol J. Chuang, Michael L. Jhaveri, Rahul R. Blease, Susan J. Manning, Anya R. Lahiri, Marc Botnar, Rene M. Levy, Daniel Larson, Martin G. O'Donnell, Christopher J. Manning, Warren J. TI Differential impact of age, sex, and hypertension on aortic atherosclerosis - The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE MRI; aortic atherosclerosis; hypertension; age; sex ID MAGNETIC-RESONANCE EVALUATION; RISK-FACTORS; YOUNG MEN; ARTERY; DISEASE; DETERMINANTS; HYPERTROPHY; ASSOCIATION; ULTRASOUND; PLAQUES AB Objective-The purpose of this study was to investigate the impact of age, sex, and hypertension (HTN) on aortic atherosclerotic burden using cardiovascular MRI (CMR) in a free-living longitudinally followed cohort. Methods and Results-1763 participants (829 M and 934 F; 38 to 88 years of age) of the Framingham Heart Study Offspring cohort underwent CMR of the thoracoabdominal aorta using an ECG-gated 2D T2-weighted black-blood sequence. Of these, 1726 subjects (96%) with interpretable CMR were characterized by sex, age-quartile, and presence or absence of HTN and clinical cardiovascular disease (CVD). Aortic plaque prevalence and volume increased with increasing age in both sexes. For the nonhypertensive (no-HTN) group, plaque was identified in 702 (46%) with greater prevalence in women than in men (P<0.006). HTN was associated with greater aortic plaque burden (P<0.02). The 200 subjects with clinical CVD had greater plaque burden than subjects without CVD (P<0.0001). Conclusions-In this free-living longitudinally followed cohort, subclinical aortic atherosclerosis was seen in nearly half of subjects and increased with advancing age. HTN was associated with increased aortic plaque burden. Among no-HTN subjects, women had greater plaque burden than men. These data suggest that subclinical atherosclerosis is more common in no-HTN women and emphasize the importance of focusing on preventive measures in both sexes. C1 [Oyama, Noriko; Salton, Carol J.; Chuang, Michael L.; Jhaveri, Rahul R.; Manning, Anya R.; Lahiri, Marc; Botnar, Rene M.; Levy, Daniel; Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Cardiovasc, Boston, MA 02215 USA. [Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Gona, Philimon; Blease, Susan J.; Larson, Martin G.] Boston Univ, Dept Math & Stat, Framingham, MA USA. [Gona, Philimon; Levy, Daniel; Larson, Martin G.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Manning, WJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Cardiovasc, 330 Brookline Ave, Boston, MA 02215 USA. EM wmanning@bidmc.harvard.edu RI Oyama-Manabe, Noriko/A-5212-2012; Botnar, Rene/E-6875-2012; OI Botnar, Rene/0000-0003-2811-2509; Larson, Martin/0000-0002-9631-1254; Lahiri, Marc/0000-0002-7616-7988 FU NHLBI NIH HHS [N01-HC-25195, R01 HL70279] NR 25 TC 38 Z9 41 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN 1 PY 2008 VL 28 IS 1 BP 155 EP 159 DI 10.1161/ATVBAHA.107.153544 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 248NE UT WOS:000252159500023 PM 17991874 ER PT J AU Helmick, CG Felson, DT Lawrence, RC Gabriel, S Hirsch, R Kwoh, CK Liang, MH Kremers, HM Mayes, MD Merkel, PA Pillemer, SR Reveille, JD Stone, JH AF Helmick, Charles G. Felson, David T. Lawrence, Reva C. Gabriel, Sherine Hirsch, Rosemarie Kwoh, C. Kent Liang, Matthew H. Kremers, Hilal Maradit Mayes, Maureen D. Merkel, Peter A. Pillemer, Stanley R. Reveille, John D. Stone, John H. CA Natl Arthritis Data Workgrp TI Estimates of the prevalence of arthritis and other rheumatic conditions in the United States SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY-BOWEL-DISEASE; PRIMARY SJOGRENS-SYNDROME; ANKYLOSING-SPONDYLITIS; REITERS-SYNDROME; PERIPHERAL ARTHRITIS; OLMSTED COUNTY; PIMA-INDIANS; CARE VISITS; EPIDEMIOLOGY AB Objective. To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by arthritis overall, rheumatoid arthritis, juvenile arthritis, the spondylarthritides, systemic lupus erythematosus, systemic sclerosis, and Sjogren's syndrome. A companion article (part II) addresses additional conditions. Methods. The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey (NHIS). For analysis of overall arthritis, we used the NHIS. Because data based on national population samples are unavailable for most specific rheumatic conditions, we-derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US population estimates from the Census Bureau, to estimate the number affected with each condition. Results. More than 21% of US adults (46.4 million persons) were found to have self-reported doctor-diagnosed arthritis. We estimated that rheumatoid arthritis affects 1.3 million adults (down from the estimate of 2.1 million for 1995), juvenile arthritis affects 294,000 children, spondylarthritides affect from 0.6 million to 2.4 million adults, systemic lupus erythematosus affects from 161,000 to 322,000 adults, systemic sclerosis affects 49,000 adults, and primary Sjogren's syndrome affects from 0.4 million to 3.1 million adults. Conclusion. Arthritis and other rheumatic conditions continue to be a large and growing public health problem. Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions, more studies generalizable to the US or addressing understudied populations are needed. C1 [Helmick, Charles G.] CDC, Arthritis Program, Atlanta, GA 30341 USA. [Felson, David T.; Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Lawrence, Reva C.] NIH, Bethesda, MD 20892 USA. [Gabriel, Sherine; Kremers, Hilal Maradit] Mayo Clin, Rochester, MN USA. [Hirsch, Rosemarie] CDC, Hyattsville, MD USA. [Kwoh, C. Kent] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Kwoh, C. Kent] Pittsburgh VA Healthcare Syst, Pittsburgh, PA USA. [Liang, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mayes, Maureen D.; Reveille, John D.] Univ Texas Houston, Hlth Sci Ctr, Houston, TX USA. [Pillemer, Stanley R.] Macrogen, Rockville, MD USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Helmick, CG (reprint author), CDC, Arthritis Program, 4770 Buford Highway,K51, Atlanta, GA 30341 USA. EM CHelmick@cdc.gov FU NIAMS NIH HHS [K24 AR002224] NR 90 TC 811 Z9 825 U1 9 U2 73 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2008 VL 58 IS 1 BP 15 EP 25 DI 10.1002/art.23177 PG 11 WC Rheumatology SC Rheumatology GA 256ML UT WOS:000252733100004 PM 18163481 ER PT J AU Lawrence, RC Felson, DT Helmick, CG Arnold, LM Choi, H Deyo, RA Gabriel, S Hirsch, R Hochberg, MC Hunder, GG Jordan, JM Katz, JN Kremers, HM Wolfe, F AF Lawrence, Reva C. Felson, David T. Helmick, Charles G. Arnold, Lesley M. Choi, Hyon Deyo, Richard A. Gabriel, Sherine Hirsch, Rosemarie Hochberg, Marc C. Hunder, Gene G. Jordan, Joanne M. Katz, Jeffrey N. Kremers, Hilal Maradit Wolfe, Frederick CA Natl Arthritis Data Workgrp TI Estimates of the prevalence of arthritis and other rheumatic conditions in the United States SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GIANT-CELL ARTERITIS; LOW-BACK-PAIN; CARPAL-TUNNEL-SYNDROME; COUNTY OSTEOARTHRITIS PROJECT; GENERAL-POPULATION; POLYMYALGIA-RHEUMATICA; KNEE OSTEOARTHRITIS; NATIONAL-HEALTH; OLMSTED COUNTY; 1990 CRITERIA AB Objective. To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by osteoarthritis, polymyalgia rheumatica and giant cell arteritis, gout, fibromyalgia, and carpal tunnel syndrome, as well as the symptoms of neck and back pain. A companion article (part 1) addresses additional conditions. Methods. The National Arthritis Data Workgroup reviewed published analyses from available national surveys, such as the National Health and Nutrition Examination Survey and the National Health Interview Survey. Because data based on national population samples are unavailable for most specific rheumatic conditions, we derived estimates from published studies of smaller, defined populations. For specific conditions, the best available prevalence estimates were applied to the corresponding 2005 US populaiion estimates from the Census Bureau, to estimate the number affected with each condition. Results. We estimated that among US adults, nearly 27 million have clinical osteoarthritis (up from the estimate of 21 million for 1995), 711,000 have polymyalgia rheumatica, 228,000 have giant cell arteritis, up to 3.0 million have had self-reported gout in the past year (up from the estimate of 2.1 million for 1995), 5.0 million have fibromyalgia, 4-10 million have carpal tunnel syndrome, 59 million have had low back pain in the past 3 months, and 30.1 million have had neck pain in the past 3 months. Conclusion. Estimates for many specific rheumatic conditions rely on a few, small studies of uncertain generalizability to the US population. This report provides the best available prevalence estimates for the US, but for most specific conditions more studies generalizable to the US or addressing understudied populations are needed. C1 [Helmick, Charles G.] CDC, Arthritis Program, Atlanta, GA 30341 USA. [Lawrence, Reva C.] NIH, Bethesda, MD 20892 USA. [Felson, David T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Arnold, Lesley M.] Univ Cincinnati, Cincinnati, OH USA. [Choi, Hyon] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gabriel, Sherine; Hunder, Gene G.; Kremers, Hilal Maradit] Mayo Clin, Rochester, MN USA. [Hirsch, Rosemarie] CDC, Hyattsville, MD USA. [Hochberg, Marc C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Jordan, Joanne M.] Univ N Carolina, Chapel Hill, NC USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wolfe, Frederick] Natl Data Bank Rheumat Dis, Wichita, KS USA. RP Helmick, CG (reprint author), CDC, Arthritis Program, 4770 Buford Highway,K51, Atlanta, GA 30341 USA. EM CHelmick@cdc.gov FU NIAMS NIH HHS [P60 AR047782, P60 AR047782-08] NR 65 TC 1564 Z9 1610 U1 18 U2 186 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2008 VL 58 IS 1 BP 26 EP 35 DI 10.1002/art.23176 PG 10 WC Rheumatology SC Rheumatology GA 256ML UT WOS:000252733100005 PM 18163497 ER PT J AU Brown, KD Claudio, E Siebenlist, U AF Brown, Keith D. Claudio, Estefania Siebenlist, Ulrich TI The roles of the classical and alternative nuclear factor-kappa B pathways: potential implications for autoimmunity and rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID COLLAGEN-INDUCED ARTHRITIS; THYMIC EPITHELIAL-CELLS; LYMPHOTOXIN-BETA-RECEPTOR; ADENOVIRAL GENE-TRANSFER; T-CELLS; SYNOVIAL FIBROBLASTS; ADAPTIVE IMMUNITY; DENDRITIC CELLS; SELF-TOLERANCE; IKK-ALPHA AB Nuclear factor-kappa B (NF-kappa B) is an inducible transcription factor controlled by two principal signaling cascades, each activated by a set of signal ligands: the classical/canonical NF-kappa B activation pathway and the alternative/noncanonical pathway. The former pathway proceeds via phosphorylation and degradation of inhibitor of NF-kappa B (I kappa B) and leads most commonly to activation of the heterodimer RelA/NF-kappa B1(p50). The latter pathway proceeds via phosphorylation and proteolytic processing of NF-kappa B2 (p100) and leads to activation, most commonly, of the heterodimer RelB/NF-kappa B2 (p52). Both pathways play critical roles at multiple levels of the immune system in both health and disease, including the autoimmune inflammatory response. These roles include cell cycle progression, cell survival, adhesion, and inhibition of apoptosis. NF-kappa B is constitutively activated in many autoimmune diseases, including diabetes type 1, systemic lupus erythematosus, and rheumatoid arthritis (RA). In this review we survey recent developments in the involvement of the classical and alternative pathways of NF-kappa B activation in autoimmunity, focusing particularly on RA. We discuss the involvement of NF-kappa B in self-reactive T and B lymphocyte development, survival and proliferation, and the maintenance of chronic inflammation due to cytokines such as tumor necrosis factor-alpha, IL-1, IL-6, and IL-8. We discuss the roles played by IL-17 and T-helper-17 cells in the inflammatory process; in the activation, maturation, and proliferation of RA fibroblast-like synovial cells; and differentiation and activation of osteoclast bone-resorbing activity. The prospects of therapeutic intervention to block activation of the NF-.B signaling pathways in RA are also discussed. C1 [Brown, Keith D.; Claudio, Estefania; Siebenlist, Ulrich] NIAID, NIH, Lab Immune Regulat, Immune Activat Sect, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIAID, NIH, Lab Immune Regulat, Immune Activat Sect, Bethesda, MD 20892 USA. EM us3n@nih.gov NR 132 TC 113 Z9 126 U1 0 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2008 VL 10 IS 4 AR 212 DI 10.1186/ar2457 PG 14 WC Rheumatology SC Rheumatology GA 356MB UT WOS:000259781200005 PM 18771589 ER PT J AU Chen, FH Tuan, RS AF Chen, Faye H. Tuan, Rocky S. TI Mesenchymal stem cells in arthritic diseases SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID MARROW STROMAL CELLS; COLLAGEN-INDUCED ARTHRITIS; BONE-MARROW; RHEUMATOID-ARTHRITIS; IN-VITRO; CHONDROGENIC DIFFERENTIATION; PROGENITOR CELLS; T-CELLS; TECHNOLOGY INSIGHT; TGF-BETA AB Mesenchymal stem cells (MSCs), the nonhematopoietic progenitor cells found in various adult tissues, are characterized by their ease of isolation and their rapid growth in vitro while maintaining their differentiation potential, allowing for extensive culture expansion to obtain large quantities suitable for therapeutic use. These properties make MSCs an ideal candidate cell type as building blocks for tissue engineering efforts to regenerate replacement tissues and repair damaged structures as encountered in various arthritic conditions. Osteoarthritis (OA) is the most common arthritic condition and, like rheumatoid arthritis (RA), presents an inflammatory environment with immunological involvement and this has been an enduring obstacle that can potentially limit the use of cartilage tissue engineering. Recent advances in our understanding of the functions of MSCs have shown that MSCs also possess potent immunosuppression and anti-inflammation effects. In addition, through secretion of various soluble factors, MSCs can influence the local tissue environment and exert protective effects with an end result of effectively stimulating regeneration in situ. This function of MSCs can be exploited for their therapeutic application in degenerative joint diseases such as RA and OA. This review surveys the advances made in the past decade which have led to our current understanding of stem cell biology as relevant to diseases of the joint. The potential involvement of MSCs in the pathophysiology of degenerative joint diseases will also be discussed. Specifically, we will explore the potential of MSC-based cell therapy of OA and RA by means of functional replacement of damaged cartilage via tissue engineering as well as their anti-inflammatory and immunosuppressive activities. C1 [Chen, Faye H.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bldg 50,50 S Dr, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health (Bethesda, MD, USA) [Z01 AR41131] FX This work was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (Bethesda, MD, USA) (Z01 AR41131). NR 88 TC 144 Z9 156 U1 1 U2 32 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2008 VL 10 IS 5 AR 223 DI 10.1186/ar2514 PG 12 WC Rheumatology SC Rheumatology GA 411JA UT WOS:000263644500016 PM 18947375 ER PT J AU Janjanin, S Djouad, F Shanti, RM Baksh, D Gollapudi, K Prgomet, D Rackwitz, L Joshi, AS Tuan, RS AF Janjanin, Sasa Djouad, Farida Shanti, Rabie M. Baksh, Dolores Gollapudi, Kiran Prgomet, Drago Rackwitz, Lars Joshi, Arjun S. Tuan, Rocky S. TI Human palatine tonsil: a new potential tissue source of multipotent mesenchymal progenitor cells SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID MARROW STROMAL CELLS; NECROSIS-FACTOR-ALPHA; IFN-GAMMA RECEPTOR; STEM-CELLS; BONE-MARROW; LYMPHOCYTE-PROLIFERATION; SYNOVIAL-MEMBRANE; INTERFERON-GAMMA; SELF-RENEWAL; T-LYMPHOCYTE AB Introduction Mesenchymal progenitor cells (MPCs) are multipotent progenitor cells in adult tissues, for example, bone marrow (BM). Current challenges of clinical application of BM-derived MPCs include donor site morbidity and pain as well as low cell yields associated with an age-related decrease in cell number and differentiation potential, underscoring the need to identify alternative sources of MPCs. Recently, MPC sources have diversified; examples include adipose, placenta, umbilicus, trabecular bone, cartilage, and synovial tissue. In the present work, we report the presence of MPCs in human tonsillar tissue. Methods We performed comparative and quantitative analyses of BM-MPCs with a subpopulation of adherent cells isolated from this lymphoid tissue, termed tonsil-derived MPCs (T-MPCs). The expression of surface markers was assessed by fluorescent-activated cell sorting analysis. Differentiation potential of T-MPCs was analyzed histochemically and by reverse transcription-polymerase chain reaction for the expression of lineage-related marker genes. The immunosuppressive properties of MPCs were determined in vitro in mixed lymphocyte reactions. Results Surface epitope analysis revealed that T-MPCs were negative for CD14, CD31, CD34, and CD45 expression and positive for CD29, CD44, CD90, and CD105 expression, a characteristic phenotype of BM-MPCs. Similar to BM-MPCs, T-MPCs could be induced to undergo adipogenic differentiation and, to a lesser extent, osteogenic and chondrogenic differentiation. T-MPCs did not express class II major histocompatibility (MHC) antigens, and in a similar but less pronounced manner compared with BM-MPCs, T-MPCs were immunosuppressive, inhibiting the proliferation of T cells stimulated by allogeneic T cells or by non-specific mitogenic stimuli via an indoleamine 2,3-dioxygenase-dependent mechanism. Conclusion Human palatine T-MPCs represent a new source of progenitor cells, potentially applicable for cell-based therapies. C1 [Janjanin, Sasa; Djouad, Farida; Shanti, Rabie M.; Baksh, Dolores; Gollapudi, Kiran; Rackwitz, Lars; Tuan, Rocky S.] NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Janjanin, Sasa; Prgomet, Drago] Univ Zagreb, Sch Med, Zagreb Clin Hosp Ctr, Dept Otorhinolaryngol Head & Neck Surg, Zagreb 10000, Croatia. [Shanti, Rabie M.; Gollapudi, Kiran] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. [Joshi, Arjun S.] George Washington Univ, Div Otolaryngol Head & Neck Surg, Washington, DC 20037 USA. RP Tuan, RS (reprint author), NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov OI Djouad, Farida/0000-0001-8248-6822 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [NIH ZO1 AR 41131]; US Department of State FX This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Intramural Research Program (NIH ZO1 AR 41131). SJ is a recipient of a Fulbright Scholarship of the US Department of State. We are grateful to Zhi Chen (Lymphocyte Cell Biology section, Molecular Immunology and Inflammation Branch, NIAMS) and Madhu Ramaswamy and Richard Siegel (Immunoregulation group, Autoimmunity Branch, NIAMS) for providing human PBMCs. NR 59 TC 38 Z9 38 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2008 VL 10 IS 4 AR R83 DI 10.1186/ar2459 PG 12 WC Rheumatology SC Rheumatology GA 356MB UT WOS:000259781200018 PM 18662393 ER PT J AU Hubbard, VS AF Hubbard, Van S. TI Commentary: Lessons learned from the development of dietary reference intakes and dietary guidelines among different countries SO ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION LA English DT Review DE nutrient requirements; dietary guidelines; nutritional monitoring AB The compilations of papers derived from the presentations at the 2(nd) Asian Network Symposium that are published concurrently in this issue offer an opportunity for the reader to gain a better understanding of the processes used for the development of country-specific nutrient reference intake recommendations and national dietary guidelines. This commentary offers a perspective of lessons learned from both the similarities and differences of approaches used among the Asian countries. Additionally, selected comparisons are made to actions and considerations related to nutrient requirements and national guidelines within the United States. It is hoped that continued dialogue among different countries on these topics should further harmonization of nutritional recommendations and provide an understanding for differences when they may occur. C1 NIH, US Dept HHS, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. RP Hubbard, VS (reprint author), NIH, US Dept HHS, Div Nutr Res Coordinat, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM hubbardv@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU H E C PRESS, HEALTHY EATING CLUB PTY LTD PI SOUTHBANK PA EMERALD HILL CLINIC 157 CLARENDON ST, SOUTHBANK, VIC 3006, AUSTRALIA SN 0964-7058 J9 ASIA PAC J CLIN NUTR JI Asia Pac. J. Clin. Nutr. PY 2008 VL 17 SU 2 BP 391 EP 393 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 300WW UT WOS:000255857200001 PM 18460436 ER PT J AU Shin, A Lee, KM Ahn, B Park, CG Park, SK Noh, DY Ahn, SH Yoo, KY Kang, D AF Shin, Aesun Lee, Kyoung-Mu Ahn, Byungchan Park, Chung-Gyu Park, Sue Kyung Noh, Dong-Young Ahn, Sei-Hyun Yoo, Keun-Young Kang, Daehee TI Genotype-phenotype Relationship between DNA Repair Gene Genetic Polymorphisms and DNA Repair Capacity SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE DNA repair; genetic polymorphisms; physiological influence; breast neoplasms ID CELL REACTIVATION ASSAY; BREAST-CANCER RISK; SISTERS DISCORDANT; XPD POLYMORPHISMS; DAMAGE; MODULATION; BRCA2 AB Genotype-phenotype relationships between genetic polymorphisms of DNA repair genes and DNA repair capacity were evaluated in a case-control study of breast cancer. Selected DNA repair genes included were those involved in double-strand break repair (ATM, XRCC2, XRCC4, XRCC6, LIG4, RAD51, RAD52), base excision repair (LIG1), nucleotide excision repair (ERCC1), and mismatch repair (hMLH1). The subjects consisted of histologically confirmed breast cancer cases (n=132) and controls (n=75) with no present or previous history of cancer. Seventeen single nucleotide polymorphisms of 10 genes (ATM-5144A>T, IVS21+1049T>C, IVS33-55T>C, IVS34+60G>A, and 3393T>G, XRCC2 31479G/A, XRCC4 921G/T, XRCC6 1796G/T, LIG4 1977T/C, RAD51 135G/C, 172G/T, RAD52 2259C/T, LIG1 583A/C, ERCC1 8092A/C, 354C/T, hMLH1 5' region -93G/A, 655A/G) were determined by TaqMan assay (ATM) or MALDI-TOF (all other genes). DNA repair capacity was measured by a host cell reactivation assay of repair of ultraviolet damage. The DNA repair capacity (%) did not differ between cases (median 37.2, interquartile range: 23.6-59.6) and controls (median 32.7, interquartile range: 26.7-53.2). However, DNA repair capacity significantly differed by the genotypes of ATM and RAD51 genes among cancer-free controls. Our findings suggest that DNA repair capacity might be influenced by genetic polymorphisms of DNA damage response genes and DNA repair genes. C1 [Park, Sue Kyung; Yoo, Keun-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Noh, Dong-Young] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Ahn, Sei-Hyun] Univ Ulsan, Coll Med, Dept Surg, Seoul, South Korea. [Ahn, Byungchan] Univ Ulsan, Dept Life Sci, Seoul, South Korea. [Lee, Kyoung-Mu] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Shin, Aesun] Natl Canc Ctr, Natl Canc Control Res Inst, Canc Prevent Div, Goyang Si, Gyeonggi Do, South Korea. RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. EM dhkang@snu.ac.kr RI Park, Chung-Gyu/C-3596-2011; Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Park, Sue Kyung/J-2757-2012; Shin, Aesun/E-9145-2014; OI Shin, Aesun/0000-0002-6426-1969; Park, Chung-Gyu/0000-0003-4083-8791 FU Ministry of Health & Welfare, Republic of Korea [0620410-1] FX This study was supported by a grant from the National R& D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0620410-1). NR 25 TC 25 Z9 25 U1 0 U2 2 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI NAGOYA PA 4-84 JOTO-CHO, KITA-KU, NAGOYA, 462-0831, JAPAN SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2008 VL 9 IS 3 BP 501 EP 505 PG 5 WC Oncology SC Oncology GA 499RQ UT WOS:000270243000025 PM 18990028 ER PT J AU Koh, KK Quon, MJ Waclawiw, MA AF Koh, Kwang Kon Quon, Michael J. Waclawiw, Myron A. TI Are statins effective for simultaneously treating dyslipidemias and hypertension? SO ATHEROSCLEROSIS LA English DT Review DE HMG-CoA reductase inhibitors; blood pressure; dyslipidemia; hypertension ID COA REDUCTASE INHIBITORS; BLOOD-PRESSURE CONTROL; RANDOMIZED CONTROLLED-TRIAL; VASCULAR SMOOTH-MUSCLE; C-REACTIVE PROTEIN; ANGIOTENSIN-II; HYPERCHOLESTEROLEMIC PATIENTS; THERAPEUTIC INTERVENTIONS; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE AB 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are unequivocally useful for lowering cholesterol levels in patients with dyslipidemias characterized by elevations in total and/or low-density lipoprotein cholesterol. The beneficial effects of statins to lower serum cholesterol translate into significant reductions in cardiovascular morbidity and mortality. In addition to lowering cholesterol levels, statins have other biological effects relevant to cardiovascular homeostasis including anti-inflammatory actions and downregulation of angiotensin type I receptor expression that contribute to improvements in endothelial function and arterial compliance. Since endothelial dysfunction and reduced arterial compliance are important pathophysiological determinants of essential hypertension, these actions of statins raise the possibility that statin therapy may be useful for simultaneously treating dyslipidemias and hypertension. However, it has been unclear whether statins are effective in lowering blood pressure. This controversy stems from a variety of methodological limitations including inadequate sample size, confounding effects of anti hypertensive drugs, differences in blood pressure measurement techniques, and differences in patient populations. However, based on published results from both small clinical studies and large randomized clinical trials, statins modestly lower blood pressure in patients with high, but not normal, blood pressure, regardless of cholesterol level. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Koh, Kwang Kon] Gachon Univ, Gil Med Ctr, Div Cardiol, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. [Quon, Michael J.] NIH, NHLBI, NCCAM, Diabet Unit,Lab Clin Invest, Bethesda, MD USA. [Waclawiw, Myron A.] NIH, NHLBI, Off Biostat Res, Bethesda, MD USA. RP Koh, KK (reprint author), Gachon Univ, Gil Med Ctr, Div Cardiol, Vasc Med & Atherosclerosis Unit, 1198 Kuwol-dong,Namdong-gu, Inchon 405760, South Korea. EM kwangk@gilhospital.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS [Z01 AT000001-06] NR 50 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2008 VL 196 IS 1 BP 1 EP 8 DI 10.1016/j.atherosclerosis.2007.06.006 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 265EI UT WOS:000253341500001 PM 17662294 ER PT B AU Suomi, SJ AF Suomi, Stephen J. BE Kline, KK TI How mother nurture helps mother nature: Scientific evidence for the protective effect of good nurturing on genetic propensity toward anxiety and alcohol abuse SO AUTHORITATIVE COMMUNITIES: THE SCIENTIFIC CASE FOR NURTURING THE WHOLE CHILD SE SEARCH INSTITUTE SERIES ON DEVELOPMENTALLY ATTENTIVE COMMUNITY AND SOCIETY LA English DT Proceedings Paper CT Children at Risk Working Conference CY JUN 24-25, 2002 CL Dartmouth Med Sch, Dartmouth, NH HO Dartmouth Med Sch ID RANGING RHESUS-MONKEYS; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; SEROTONIN TRANSPORTER AVAILABILITY; NONHUMAN PRIMATE MODEL; SEVERE AGGRESSION; EARLY EXPERIENCE; PLASMA-CORTISOL; BEHAVIOR; CONSUMPTION; SEPARATION C1 [Suomi, Stephen J.] Natl Inst Hlth, Bethesda, MD USA. NR 61 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-72720-2 J9 SEARCH INST SER DEV PY 2008 BP 87 EP 102 PG 16 WC Psychology, Biological; Family Studies; Psychology, Developmental; Sociology SC Psychology; Family Studies; Sociology GA BHO99 UT WOS:000254976600003 ER PT S AU Heuer, L Ashwood, P Van de Water, J AF Heuer, Luke Ashwood, Paul Van de Water, Judy BE Zimmerman, AW TI The Immune System in Autism Is There a Connection? SO AUTISM: CURRENT THEORIES AND EVIDENCE SE Current Clinical Neurology LA English DT Article; Book Chapter DE Autism; immunology; maternal; autoantibodies; fetus ID CENTRAL-NERVOUS-SYSTEM; DISEASE VIRUS-INFECTION; BLOOD-BRAIN-BARRIER; SPECTRUM DISORDERS; ANTIBRAIN ANTIBODIES; POSSIBLE ASSOCIATION; AUTOIMMUNE-DISEASE; INDUCE ACTIVATION; MONONUCLEAR-CELLS; IMMUNOGLOBULIN-G AB Autistic spectrum disorders (ASD) are a broad spectrum of heterogeneous neurodevelopmental disorders, most with unknown etiology. Although the development of autism is suspected to be the result of a complex combination of genetic, environmental, neurobiological, and immunological factors, the role of each of these factors is still under investigation. In this chapter, we review current concepts regarding the immunological aspects of autism as they pertain to areas of our own research. Three specific areas are covered including autoantibodies in children with ASD, maternal antibodies directed against fetal brain, and immune dysfunction in children with ASD. C1 [Heuer, Luke; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, NIEHS, MIND Inst,Ctr Childrens Environm Hlth, Davis, CA 95616 USA. [Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, NIEHS, MIND Inst,Ctr Childrens Environm Hlth, Davis, CA 95616 USA. RP Van de Water, J (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, NIEHS, MIND Inst,Ctr Childrens Environm Hlth, 451 E Hlth Sci Dr,Suite 6510 GBSF, Davis, CA 95616 USA. EM javandewater@ucdavis.edu NR 124 TC 7 Z9 7 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1559-0585 BN 978-1-60327-488-3 J9 CURR CLIN NEUROL JI Cur. Clin. Neurol. PY 2008 BP 271 EP 288 DI 10.1007/978-1-60327-489-0_12 D2 10.1007/978-1-60327-489-0 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA BKA00 UT WOS:000267560100013 ER PT J AU Ehrlich, M Sanchez, C Shao, C Nishiyama, R Kehrl, J Kuick, R Kubota, T Hanash, SM AF Ehrlich, Melanie Sanchez, Cecilia Shao, Chunbo Nishiyama, Rie Kehrl, John Kuick, Rork Kubota, Takeo Hanash, Samir M. TI ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation SO AUTOIMMUNITY LA English DT Review DE immunodeficiency; constitutive heterochromatin; cancer; DNA methyltransferases; chromosomal rearrangements; DNA demethylation ID KINASE-C-ETA; FAS-ASSOCIATED PHOSPHATASE-1; NITRIC-OXIDE SYNTHASE; DE-NOVO METHYLATION; NF-KAPPA-B; OXYGENASE-1-DERIVED CARBON-MONOXIDE; PROTEIN-TYROSINE-PHOSPHATASE; LYMPHOBLASTOID CELL-LINES; SOLUBLE GUANYLATE-CYCLASE; CLASSICAL SATELLITE DNA AB The immunodeficiency, centromeric region instability, and facial anomalies syndrome (ICF) is the only disease known to result from a mutated DNA methyltransferase gene, namely, DNMT3B. Characteristic of this recessive disease are decreases in serum immunoglobulins despite the presence of B cells and, in the juxtacentromeric heterochromatin of chromosomes 1 and 16, chromatin decondensation, distinctive rearrangements, and satellite DNA hypomethylation. Although DNMT3B is involved in specific associations with histone deacetylases, HP1, other DNMTs, chromatin remodelling proteins, condensin, and other nuclear proteins, it is probably the partial loss of catalytic activity that is responsible for the disease. In microarray experiments and real-time RT-PCR assays, we observed significant differences in RNA levels from ICF vs. control lymphoblasts for pro- and anti-apoptotic genes (BCL2L10, CASP1, and PTPN13); nitrous oxide, carbon monoxide, NF-B, and TNF signalling pathway genes (PRKCH, GUCY1A3, GUCY1B3, MAPK13; HMOX1, and MAP4K4); and transcription control genes (NR2F2 and SMARCA2). This gene dysregulation could contribute to the immunodeficiency and other symptoms of ICF and might result from the limited losses of DNA methylation although ICF-related promoter hypomethylation was not observed for six of the above examined genes. We propose that hypomethylation of satellite 2 at 1qh and 16qh might provoke this dysregulation gene expression by trans effects from altered sequestration of transcription factors, changes in nuclear architecture, or expression of noncoding RNAs. C1 [Ehrlich, Melanie; Shao, Chunbo] Tulane Med Sch, Haywards Human Genet Program, New Orleans, LA 70112 USA. [Sanchez, Cecilia] Tulane Med Sch, Ctr Gene Therapy, New Orleans, LA 70112 USA. [Nishiyama, Rie] RIKEN, Ctr Plasma Sci, Ibaraki 3050074, Japan. [Kehrl, John] NIAID, Bethesda, MD 20892 USA. [Kuick, Rork] Univ Michigan, Ctr Comprehens Canc, Biostat Core, Ann Arbor, MI 48109 USA. [Kubota, Takeo] Univ Yamanashi, Yamanashi, Japan. [Hanash, Samir M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Ehrlich, M (reprint author), Tulane Med Sch, Haywards Human Genet Program, 1430 Tulane Ave, New Orleans, LA 70112 USA. EM ehrlich@tulane.edu RI Shao, Chunbo/C-5412-2011; feng, jian/G-9313-2011; OI Kehrl, John/0000-0002-6526-159X FU NCI NIH HHS [R01 CA081506, CA81506] NR 174 TC 65 Z9 66 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 2008 VL 41 IS 4 BP 253 EP 271 DI 10.1080/08916930802024202 PG 19 WC Immunology SC Immunology GA 292NV UT WOS:000255274300003 PM 18432406 ER PT J AU Gills, JJ LoPiccolo, J Dennis, PA AF Gills, Joell J. LoPiccolo, Jaclyn Dennis, Phillip A. TI Nelfinavir, a new anti-cancer drug with pleiotropic effects and many paths to autophagy SO AUTOPHAGY LA English DT Article DE HIV protease inhibitor; nelfinavir; Akt; ER stress; eukaryotic elongation factor 2 ID ENDOPLASMIC-RETICULUM STRESS; ELONGATION-FACTOR-2 KINASE; CANCER-CELLS; PHOSPHORYLATION AB The development of cancer drugs is slow and costly. One approach to accelerate the availability of new drugs is to reposition drugs approved for other indications as anti-cancer agents. HIV protease inhibitors (HIV PIs) are useful in treating HIV infection and cause toxicities in humans that are similar to those observed when the kinase Akt, a target for cancer therapy, is inhibited. To test whether HIV PIs inhibited Akt and cancer cell proliferation, we screened 6 HIV PIs and found that three, ritonavir, saquinavir and nelfinavir, inhibit the growth of over 60 cancer cell lines derived from 9 different tumor types; Nelfinavir is the most potent. Nelfinavir causes caspase-dependent apoptosis and non-apoptotic death, as well as endoplasmic reticulum (ER) stress and autophagy, Nelfinavir blocks growth factor receptor activation and decreases growth factor-induced and endogenous Akt signaling. In vivo, nelfinavir inhibits tumor growth and upregulates markers of ER stress, autophagy and apoptosis. Nelfinavir is currently being tested in cancer patients in Phase I clinical trials where biomarkers will be assessed. Current studies are focused on measuring autophagy in clinical specimens and identifying combination strategies that will exploit the induction of autophagy and increase the effectiveness of nelfinavir. C1 [Gills, Joell J.; LoPiccolo, Jaclyn; Dennis, Phillip A.] NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. RP Dennis, PA (reprint author), NCI Navy Med Oncol, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 16 TC 55 Z9 56 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JAN 1 PY 2008 VL 4 IS 1 BP 107 EP 109 PG 3 WC Cell Biology SC Cell Biology GA 249FB UT WOS:000252211800023 PM 18000394 ER PT J AU Otto, M AF Otto, M. TI Staphylococcal biofilms SO BACTERIAL BIOFILMS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID POLYSACCHARIDE INTERCELLULAR ADHESIN; ACCUMULATION-ASSOCIATED PROTEIN; CATHETER-ASSOCIATED INFECTION; INDWELLING MEDICAL DEVICES; SEQUENCE ELEMENT IS256; GRAM-POSITIVE BACTERIA; FOREIGN-BODY INFECTION; QUORUM-SENSING SYSTEM; CELL-WALL; EPIDERMIDIS BIOFILMS AB Staphylococcus epidermidis and Staphylococcus aureus are the most frequent causes of nosocomial infections and infections on indwelling medical devices, which characteristically involve biofilms. Recent advances in staphylococcal molecular biology have provided more detailed insight into the basis of biofilm formation in these opportunistic pathogens. A series of surface proteins mediate initial attachment to host matrix proteins, which is followed by the expression of a cationic glucosamine-based exopolysaccharide that aggregates the bacterial cells. In some cases, proteins may function as alternative aggregating substances. Furthermore, surfactant peptides have now been recognized as key factors involved in generating the three-dimensional structure of a staphylococcal biofilm by cell-cell disruptive forces, which eventually may lead to the detachment of entire cell clusters. Transcriptional profiling experiments have defined the specific physiology of staphylococcal bioflms and demonstrated that biofilm resistance to antimicrobials is due to gene-regulated processes. Finally, novel animal models of staphylococcal biofilm-associated infection have given us important information on which factors define biofilm formation in vivo. These recent advances constitute an important basis for the development of anti-staphylococcal drugs and vaccines. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS [Z99 AI999999, ZIA AI001080-02] NR 102 TC 355 Z9 364 U1 12 U2 79 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 2008 VL 322 BP 207 EP 228 PG 22 WC Immunology; Microbiology SC Immunology; Microbiology GA BID23 UT WOS:000258523900010 PM 18453278 ER PT J AU Hinnebusch, BJ Erickson, DL AF Hinnebusch, B. J. Erickson, D. L. TI Yersinia pestis biofilm in the flea vector and its role in the transmission of plague SO BACTERIAL BIOFILMS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID STORAGE HMS(+) PHENOTYPE; POLYSACCHARIDE INTERCELLULAR ADHESIN; ENTERICA SEROVAR TYPHIMURIUM; CYCLIC DI-GMP; STAPHYLOCOCCUS-EPIDERMIDIS; CAENORHABDITIS-ELEGANS; BACTERIAL BIOFILMS; BUBONIC PLAGUE; PASTEURELLA-PESTIS; PLASMINOGEN-ACTIVATOR AB Transmission by fleabite is a relatively recent evolutionary adaptation of Yersinia pestis, the bacterial agent of bubonic plague. To produce a transmissible infection, Y. pestis grows as an attached biolilm in the foregut of the flea vector. Biofilm formation both in the flea foregut and in vitro is dependent on an extracellular matrix (ECM) synthesized by the Yersinia hms gene products. The hms genes are similar to the pga and ica genes of Escherichia coli and Staphylococcus epidermidis, respectively, that act to synthesize a poly-beta-1.6-N-acetyl-d-glucosamine ECM required for biolilm formation. As with extracellular polysaccharide production in many other bacteria, synthesis of the Hms-dependent ECM is controlled by intracellular levels of cyclic-di-GMP. Yersinia pseudotuberculosis, the food- and water-borne enteric pathogen from which Y. pestis evolved recently, possesses identical hms genes and can form biofilm in vitro but not in the flea. The genetic changes in Y. pestis that resulted in adapting biofilm-forming capability to the flea gut environment, a critical step in the evolution of vector-borne transmission, have yet to be identified. During a flea bite, Y. pestis is regurgitated into the dermis in a unique biofilm phenotype, and this has implications for the initial interaction with the mammalian innate immune response. C1 [Hinnebusch, B. J.; Erickson, D. L.] NIAID, Rocky Mt Labs, NIH, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Rocky Mt Labs, NIH, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. EM jhinnebusch@niaid.nih.gov FU NIH, NIAID FX This work was supported by the Intramural Research Program of the NIH, NIAID. NR 107 TC 52 Z9 58 U1 1 U2 10 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 2008 VL 322 BP 229 EP 248 PG 20 WC Immunology; Microbiology SC Immunology; Microbiology GA BID23 UT WOS:000258523900011 PM 18453279 ER PT J AU Das, S Chen, MH Kim, S Warren, N AF Das, Sonali Chen, Ming-Hui Kim, Sungduk Warren, Nicholas TI A Bayesian Structural Equations Model for Multilevel Data with Missing Responses and Missing Covariates SO BAYESIAN ANALYSIS LA English DT Article DE DIC; Latent variable; Markov chain Monte Carlo; missing at random; random effects; VHA all employee survey data AB Motivated by a large multilevel survey conducted by the US Veterans Health Administration (VHA), we propose a structural equations model which involves a set of latent variables to capture dependence between different responses, a set of facility level random effects to capture facility heterogeneity and dependence between individuals within the same facility, and a set of covariates to account for individual heterogeneity. Identifiability associated with structural equations modeling is addressed and properties of the proposed model are carefully examined. An effective and practically useful modeling strategy is developed to deal with missing responses and to model missing covariates in the structural equations framework. Markov chain Monte Carlo sampling is used to carry out Bayesian posterior computation. Several variations of the proposed model are considered and compared via the deviance information criterion. A detailed analysis of the VHA all employee survey data is presented to illustrate the proposed methodology. C1 [Das, Sonali] CSIR BE, Pretoria, South Africa. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Kim, Sungduk] NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [Warren, Nicholas] Univ Connecticut, Ctr Hlth, Farmington, CT USA. RP Das, S (reprint author), CSIR BE, Pretoria, South Africa. EM sdas@csir.co.za; mhchen@stat.uconn.edu; kims2@mail.nih.gov; warren@nso.uchc.edu FU Veterans Health Administration; National Center for Organizational Development FX The authors wish to thank the Editor-in-Chief, the Editor, the Associate Editor, and the two referees for their helpful comments and suggestions which have led to an improvement of this article. The authors also wish to acknowledge and thank the Veterans Health Administration and the National Center for Organizational Development for access to the All Employee Survey (AES) 1997 data and their substantial efforts to insure the quality and integrity of these data. NR 37 TC 7 Z9 8 U1 0 U2 1 PU INT SOC BAYESIAN ANALYSIS PI PITTSBURGH PA CARNEGIE MELLON UNIV, DEPT STTISTICS, PITTSBURGH, PA 15213 USA SN 1931-6690 J9 BAYESIAN ANAL JI Bayesian Anal. PY 2008 VL 3 IS 1 BP 197 EP 224 PG 28 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA V10HJ UT WOS:000207454800011 ER PT J AU Chen, MH Huang, L Ibrahim, JG Kim, S AF Chen, Ming-Hui Huang, Lan Ibrahim, Joseph G. Kim, Sungduk TI Bayesian Variable Selection and Computation for Generalized Linear Models with Conjugate Priors SO BAYESIAN ANALYSIS LA English DT Article DE Bayes factor; Conditional Predictive Ordinate; Conjugate prior; L measure; Poisson regression; Logistic regression AB In this paper, we consider theoretical and computational connections between six popular methods for variable subset selection in generalized linear models (GLM's). Under the conjugate priors developed by Chen and Ibrahim (2003) for the generalized linear model, we obtain closed form analytic relationships between the Bayes factor (posterior model probability), the Conditional Predictive Ordinate (CPO), the L measure, the Deviance Information Criterion (DIC), the Aikiake Information Criterion (AIC), and the Bayesian Information Criterion (BIC) in the case of the linear model. Moreover, we examine computational relationships in the model space for these Bayesian methods for an arbitrary GLM under conjugate priors as well as examine the performance of the conjugate priors of Chen and Ibrahim (2003) in Bayesian variable selection. Specifically, we show that once Markov chain Monte Carlo (MCMC) samples are obtained from the full model, the four Bayesian criteria can be simultaneously computed for all possible subset models in the model space. We illustrate our new methodology with a simulation study and a real dataset. C1 [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Huang, Lan] NCI, SRAB, Rockville, MD USA. [Ibrahim, Joseph G.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Kim, Sungduk] NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. RP Chen, MH (reprint author), Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. EM huangla@mail.nih.gov; ibrahim@bios.unc.edu; kims2@mail.nih.gov FU NIH [GM 70335, CA 74015] FX The authors wish to thank the Editor-in-Chief, the Editor, the Associate Editor, and the two referees for their helpful comments and suggestions, which have improved the paper. This research was partially supported by NIH grants # GM 70335 and # CA 74015. NR 45 TC 12 Z9 12 U1 1 U2 5 PU INT SOC BAYESIAN ANALYSIS PI PITTSBURGH PA CARNEGIE MELLON UNIV, DEPT STTISTICS, PITTSBURGH, PA 15213 USA SN 1931-6690 EI 1936-0975 J9 BAYESIAN ANAL JI Bayesian Anal. PY 2008 VL 3 IS 3 BP 585 EP 613 DI 10.1214/08-BA323 PG 29 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA V10HL UT WOS:000207455000012 PM 19436774 ER PT J AU Lecona, E Olmo, N Turnay, J Santiago-Gomez, A De Silanes, IL Gorospe, M Lizarbe, MA AF Lecona, Emilio Olmo, Nieves Turnay, Javier Santiago-Gomez, Angelica De Silanes, Isabel Lopez Gorospe, Myriam Lizarbe, M. Antonia TI Kinetic analysis of butyrate transport in human colon adenocarcinoma cells reveals two different carrier-mediated mechanisms SO BIOCHEMICAL JOURNAL LA English DT Article DE anion exchanger; butyrate uptake; colon adenocarcinoma; monocarboxylate transporter; protein kinase C (PKC) activator; small interfering RNA (siRNA) ID CHAIN FATTY-ACIDS; RAT DISTAL COLON; MONOCARBOXYLATE TRANSPORTER; CACO-2 CELLS; MEMBRANE; LACTATE; MCT1; LOCALIZATION; EXPRESSION AB Butyrate has antitumorigenic effects on colon cancer cells, inhibits cell growth and promotes differentiation and apoptosis. These effects depend on its intracellular concentration, which is regulated by its transport. We have analysed butyrate uptake kinetics in human colon adenocarcinoma cells sensitive to the apoptotic effects of butyrate (BCS-TC2, Caco-2 and HT-29), in butyrate-resistant cells (BCS-TC2.BR2) and in normal colonic cells (FHC). The properties of transport were analysed with structural analogues, specific inhibitors and different bicarbonate and sodium concentrations. Two carrier-mediated mechanisms were detected: a low-affinity/high-capacity (K-m = 109 +/- 16 mM in BCS-TC2 cells) anion exchanger and a high-affinity/low-capacity (K-m = 17.9 +/- 4.0 mu M in BCS-TC2 cells) proton-monocarboxylate co-transporter that was energy-dependent and activated via PKC delta (protein kinase C delta). All adenocarcinoma cells analysed express MCT (monocarboxylate transporter) 1, MCT4, ancillary protein CD 147 and AE2 (anion exchanger 2). Silencing experiments show that MCT1, whose expression increases with butyrate treatment in butyrate-sensitive cells, plays a key role in high-affinity transport. Low-affinity uptake was mediated by a butyrate/bicarbonate antiporter along with a possible contribution of AE2 and MCT4. Butyrate treatment increased uptake in a time- and dose-dependent manner in butyrate-sensitive but not in butyrate-resistant cells. The two butyrate-uptake activities in human colon adenocarcinoma cells enable butyrate transport at different physiological conditions to maintain cell functionality. The high-affinity/low-capacity transport functions under low butyrate concentrations and may be relevant for the survival of carcinoma cells in tumour regions with low glucose and butyrate availability as well as for the normal physiology of colonocytes. C1 [Lecona, Emilio; Olmo, Nieves; Turnay, Javier; Santiago-Gomez, Angelica; Lizarbe, M. Antonia] Univ Complutense Madrid, Fac Chem, Dept Biochem & Mol Biol 1, E-28040 Madrid, Spain. [De Silanes, Isabel Lopez; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Lizarbe, MA (reprint author), Univ Complutense Madrid, Fac Chem, Dept Biochem & Mol Biol 1, E-28040 Madrid, Spain. EM lizarbe@bbm1.ucm.es RI Lizarbe, M Antonia/K-5219-2014; Turnay, Javier/K-4551-2014; OLMO LOPEZ, NIEVES/K-5266-2014; Lopez de Silanes, Isabel/K-4962-2015 OI Lizarbe, M Antonia/0000-0003-1722-1240; Turnay, Javier/0000-0002-6135-2179; OLMO LOPEZ, NIEVES/0000-0002-8013-5313; Lopez de Silanes, Isabel/0000-0001-6762-9792 NR 38 TC 27 Z9 27 U1 0 U2 7 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 2008 VL 409 BP 311 EP 320 DI 10.1042/BJ20070374 PN 1 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 251ZJ UT WOS:000252414300031 PM 17760565 ER PT J AU Rothman, RB Baumann, MH Prisinzano, TE Newman, AH AF Rothman, Richard B. Baumann, Michael H. Prisinzano, Thomas E. Newman, Amy Hauck TI Dopamine transport inhibitors based on GBR12909 and benztropine as potential medications to treat cocaine addiction SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE cocaine; GBR12909; benztropine; dopamine transporter; dopamine uptake inhibitor; medication discovery ID ABUSE THERAPEUTIC AGENTS; MONOAMINE REUPTAKE INHIBITORS; MOLECULAR-FIELD ANALYSIS; RHESUS-MONKEYS; PHARMACOLOGICAL CHARACTERIZATION; NONHUMAN-PRIMATES; 3-ALPHA-(DIPHENYLMETHOXY)TROPANE ANALOGS; 3-ALPHA-DIPHENYLMETHOXYTROPANE ANALOGS; BEHAVIORAL PHARMACOLOGY; PRECLINICAL EVALUATION AB The discovery and development of medications to treat addiction and notably, cocaine addiction, have been frustrated by both the complexity of the disorder and the lack of target validation in human subjects. The dopamine transporter has historically been a primary target for cocaine abuse medication development, but addictive liability and other confounds of such inhibitors of dopamine uptake have limited clinical evaluation and validation. Herein we describe efforts to develop analogues of the dopamine uptake inhibitors GBR 12909 and benztropine that show promising profiles in animal models of cocaine abuse that contrast to that of cocaine. Their unique pharmacological profiles have provided important insights into the reinforcing actions of cocaine and we propose that clinical investigation of novel dopamine uptake inhibitors will facilitate the discovery of cocaine-abuse medications. Published by Elsevier Inc. C1 [Newman, Amy Hauck] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, Natl Inst Hlth, Baltimore, MD 21224 USA. [Rothman, Richard B.; Baumann, Michael H.] Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, Natl Inst Hlth, Baltimore, MD 21224 USA. [Prisinzano, Thomas E.] Univ Iowa, Iowa City, IA USA. RP Newman, AH (reprint author), Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, Natl Inst Hlth, 333 Cassell Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov RI Prisinzano, Thomas/B-7877-2010 FU Intramural NIH HHS [Z01 DA000389-12, Z99 DA999999] NR 96 TC 46 Z9 47 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 1 PY 2008 VL 75 IS 1 BP 2 EP 16 DI 10.1016/j.bcp.2007.08.007 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 252YU UT WOS:000252484800002 PM 17897630 ER PT J AU Uhl, GR Drgon, T Johnson, C Fatusin, OO Liu, QR Contoreggi, C Li, CY Buck, K Crabbe, J AF Uhl, George R. Drgon, Tomas Johnson, Catherine Fatusin, Olutuatosin O. Liu, Qing-Rong Contoreggi, Carlo Li, Chuan-Yun Buck, Kari Crabbe, John TI "Higher order" addiction molecular genetics: Convergent data from genome-wide association in humans and mice SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE association genome scanning; substance dependence; microarray; pooled; neuronal connections ID ALDEHYDE DEHYDROGENASE GENOTYPES; ALCOHOL-METABOLIZING GENES; CELL-ADHESION MOLECULES; POPULATION-BASED SAMPLE; MILD MENTAL IMPAIRMENT; INBRED MOUSE STRAINS; NICOTINE DEPENDENCE; SUSCEPTIBILITY LOCI; LINKAGE ANALYSIS; SUBSTANCE-ABUSE AB Family, adoption and twin data each support substantial heritability for addictions. Most of this heritable influence is not substance-specific. The overlapping genetic vulnerability for developing dependence on a variety of addictive substances suggests large roles for "higher order" pharamacogenomics in addiction molecular genetics. We and others have now completed genome-wide association (GWA) studies of DNAs from individuals with dependence on a variety of addictive substances versus appropriate controls. Recently reported replicated GWA observations identify a number of genes based on comparisons between controls and European-American and African-American polysubstance abusers. Here we review the convergence between these results and data that compares control samples and (a) alcohol-dependent European-Americans, (b) methamphetamine-dependent Asians and (c) nicotine dependent samples from European backgrounds. We also compare these human data to quantitative trait locus (QTL) results from studies of addiction-related phenotypes in mice that focus on alcohol, methamphetamine and barbiturates. These comparisons support a genetic architecture built from largely polygenic contributions of common allelic variants to dependence on a variety of legal and illegal substances. Many of the gene variants identified in this way are likely to alter specification and maintenance of neuronal connections. Published by Elsevier Inc. C1 [Uhl, George R.; Drgon, Tomas; Johnson, Catherine; Fatusin, Olutuatosin O.; Liu, Qing-Rong] NIDA, Mol Neurobiol Branch, NIH, IRP, Baltimore, MD 21224 USA. [Contoreggi, Carlo] NIDA, Off Clin Director, NIH, IRP, Baltimore, MD 21224 USA. [Li, Chuan-Yun] Peking Univ, Coll Life Sci, Ctr Bioinformat, Beijing 100871, Peoples R China. [Buck, Kari; Crabbe, John] Oregon Hlth & Sci Univ, Potland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA. [Buck, Kari; Crabbe, John] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Uhl, GR (reprint author), Box 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS [Z01 DA000165-12, Z01 DA000401-10, Z01 DA000492-02]; NIAAA NIH HHS [AA011114, AA10760, P60 AA010760, R01 AA011114, R29 AA011114]; NIDA NIH HHS [DA05228, R01 DA005228] NR 99 TC 66 Z9 67 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 1 PY 2008 VL 75 IS 1 BP 98 EP 111 DI 10.1016/j.bcp.2007.06.042 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 252YU UT WOS:000252484800009 PM 17764662 ER PT J AU Wilbur, DS Hamlin, DK Chyan, MK Brechbiel, MW AF Wilbur, D. Scott Hamlin, Donald K. Chyan, Ming-Kuan Brechbiel, Martin W. TI Streptavidin in antibody pretargeting. 5. Chemical modification of recombinant streptavidin for labeling with the alpha-particle-emitting radionuclides Bi-213 and At-211 SO BIOCONJUGATE CHEMISTRY LA English DT Article ID AT-211-LABELED MONOCLONAL-ANTIBODY; IN-VIVO BIODISTRIBUTION; B-CELL LYMPHOMAS; CARCINOMA XENOGRAFTS; CHX-DTPA; RADIOLABELED STREPTAVIDIN; BIOTINYLATED ANTIBODY; THERAPEUTIC-EFFICACY; CANCER-THERAPY; MURINE MODEL AB We are investigating, the use of recombinant streptavidin (rSAv) as a carrier molecule for the short-lived alpha-particle emitting radionuclides Bi-213 (t(1/2) = 45.6 min) and At-211 (t(1/2) = 7.21 h) in cancer therapy. To utilize rSAv as a carrier, it must be modified in a manner that permits rapid chelation or bonding with these short-lived radionuclides and also modified in a manner that diminishes its natural propensity for localization in the kidney. Modification for labeling with Bi-213 was accomplished by conjugation of rSAv with the DTPA derivative p-isothiocyanatobenzyl-CHX-A '' (CHX-A ''), 3a. Modification for direct labeling with At-211 was accomplished by conjugation of rSAv with an isothiocyanatophenyl derivative of a nido-carborane (nCB), 3b, or an isothiocyanatophenyl-dPEG/decaborate(2-) derivative, 3c. After conjugation of the chelating or bonding moiety, rSAv was further modified by reaction with an excess (50-100 equivalents) of succinic anhydride. Succinylation of the lysine amines has previously been shown to greatly diminish kidney localization. rSAv modified by conjugation with 3a and succinylated rapidly radiolabeled with Bi-213 (<5 min), providing a 72% isolated yield. At-211 labeling of modified rSAv was accomplished in aqueous solution using chloramine-T as the oxidant. Astatination of rSAv conjugated with 3b and succinylated occurred very rapidly (<1 min), providing a 50% isolated radiochemical yield. Astatination of rSAv conjugated with 3c and succinylated was also very rapid (< 1 min) providing 66-71% isolated radiochemical yields. Astatination of succinylated rSAv, 2a, which did not have conjugated borane cage moieties, resulted in a much lower radiolabeling yield (18%). The Bi-213 or At-211-labeled modified rSAv preparations were mixed with the corresponding I-125-labeled rSAv, and dual-label in vivo distributions were obtained in athymic mice. The in vivo data show that Bi-213-labeled succinylated rSAv [Bi-213]6a has tissue concentrations similar to those of I-125- labeled modified rSAv [I-125]6b, suggesting that Bi-213 is quite stable toward release from the chelate in vivo. In vivo data also indicate that the At-211-labeled rSAv conjugated with 3b or 3c and succinylated are stable to in vivo deastatination, whereas succinylated rSAv lacking a boron cage moiety is subject to some deastatination. The modified rSAv conjugated with nido-carborane derivative 3b has a higher retention in many tissues than rSAv without the carborane conjugated. Interestingly, the rSAv conjugated with 3c, which also contains an m-dPEG(12) moiety, has significantly decreased concentrations in blood and other tissues when compared with those of direct-labeled rSAv, suggesting that it may be a good candidate for further study. In conclusion, rSAv that has been modified with CHX-A '' and succinylated (i.e., 5a) may be useful as a carrier of Bi-213. The encouraging results obtained with the PEGylated decaborate(2-) derivative 3c and succinylated (i.e., 5c) suggests that its further study as a carrier of At-211 in pretargeting protocols is warranted. C1 [Wilbur, D. Scott; Hamlin, Donald K.; Chyan, Ming-Kuan] Univ Washington, Dept Radiat Oncol, Seattle, WA 98105 USA. [Brechbiel, Martin W.] NCI, NIH, Bethesda, MD 20892 USA. RP Wilbur, DS (reprint author), Univ Washington, Dept Radiat Oncol, Box 355016,616 NE Northlake Pl, Seattle, WA 98105 USA. EM dswilbur@u.washington.edu FU Intramural NIH HHS; NCI NIH HHS [R01 CA113431-03, R01 CA113431, 5 R01 CA113431] NR 72 TC 10 Z9 10 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2008 VL 19 IS 1 BP 158 EP 170 DI 10.1021/bc7002428 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 253LS UT WOS:000252520300022 PM 18072725 ER PT J AU Otto, M AF Otto, Michael TI Targeted immunotherapy for staphylococcal infections - Focus on anti-MSCRAMM antibodies SO BIODRUGS LA English DT Article ID CLUMPING FACTOR-A; POLYSACCHARIDE CONJUGATE VACCINE; FIBRONECTIN-BINDING PROTEIN; CAPSULAR POLYSACCHARIDE; AUREUS INFECTIONS; IMMUNE EVASION; NASAL CARRIAGE; EPIDERMIDIS INFECTIONS; NOSOCOMIAL INFECTIONS; PROTECTIVE EFFICACY AB Staphylococcal infections represent an enormous burden to the public health system in the US and worldwide. While traditionally restricted to the hospital setting, highly virulent strains have recently emerged that may cause severe, even fatal, disease in healthy adults outside healthcare settings. This situation, together with the increasing resistance to many antibacterials in a wide variety of staphylococcal strains, requires that vaccine development for staphylococcal diseases be re-evaluated. Finding a vaccine for staphylococci is not trivial, as protective immunity to staphylococcal infections does not appear to exist at a significant degree, which may be partly due to the fact that our immune system is in constant contact with staphylococcal antigens and many strains are commensal organisms on human epithelia. Furthermore, the most virulent species, Staphylococcus aureus, produces protein A, a powerful means to evade acquired host defense. While two high-profile vaccine preparations have failed clinical trials within the last few years, promising results from novel approaches based on the combination of systematically selected antigens have been reported. These combinatory vaccines target microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), a family of bacterial proteins that bind to human extracellular matrix components. In addition, polysaccharide and other nonprotein antigens may represent suitable vaccine targets on the staphylococcal cell surface. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS NR 72 TC 34 Z9 35 U1 0 U2 1 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2008 VL 22 IS 1 BP 27 EP 36 PG 10 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 284AB UT WOS:000254676500003 PM 18215088 ER PT J AU Mason, JM Frydrychova, RC Biessmann, H AF Mason, James M. Frydrychova, Radmila Capkova Biessmann, Harald TI Drosophila telomeres: an exception providing new insights SO BIOESSAYS LA English DT Review ID HET-A RETROPOSONS; CHROMOSOME ENDS; HETEROCHROMATIN PROTEIN-1; P-ELEMENT; DNA-SEQUENCES; MELANOGASTER TELOMERES; GENOMIC ORGANIZATION; HISTONE MODIFICATION; DIFFERENT MECHANISMS; MAMMALIAN TELOMERES AB Drosophila telomeres comprise DNA sequences that differ dramatically from those of other eukaryotes. Telomere functions, however, are similar to those found in telomerase-based telomeres, even though the underlying mechanisms may differ. Drosophila telomeres use arrays of retrotransposons to maintain chromosome length, while nearly all other eukaryotes rely on telomerase-generated short repeats. Regardless of the DNA sequence, several end-binding proteins are evolutionarily conserved. Away from the end, the Drosophila telomeric and subtelomeric DNA sequences are complexed with unique combinations of proteins that also modulate chromatin structure elsewhere in the genome. Maintaining and regulating the transcriptional activity of the telomeric retrotransposons in Drosophila requires specific chromatin structures and, while telomeric silencing spreads from the terminal repeats in yeast, the source of telomeric silencing in Drosophila is the subterminal arrays. However, the subterminal arrays in both species may be involved in telomere-telomere associations and/or communication. C1 [Biessmann, Harald] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. [Mason, James M.; Frydrychova, Radmila Capkova] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC USA. RP Biessmann, H (reprint author), Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. EM hbiessma@uci.edu RI Capkova Frydrychova, Radmila/H-4187-2014 FU Intramural NIH HHS [Z01 ES101764-04]; NIGMS NIH HHS [GM-56729, R01 GM056729] NR 105 TC 68 Z9 71 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2008 VL 30 IS 1 BP 25 EP 37 DI 10.1002/bies.20688 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 250XM UT WOS:000252334600005 PM 18081009 ER PT J AU Gandia, J Lluis, C Ferre, S Franco, R Ciruela, F AF Gandia, Jorge Lluis, Carme Ferre, Sergi Franco, Rafael Ciruela, Francisco TI Light resonance energy transfer-based methods in the study of G protein-coupled receptor oligomerization SO BIOESSAYS LA English DT Article ID A(1) ADENOSINE RECEPTORS; LIVING CELLS; TRANSFER BRET; QUANTITATIVE ASSESSMENT; HORMONE-RECEPTOR; FLUORESCENCE; ACTIVATION; MEMBRANE; FRET; SURFACE AB Since most of the functions in cells are mediated by multimeric protein complexes, the determination of protein-protein interactions is an important step in the study of cellular mechanisms. Traditionally, after screening for possible target interactors by means of a yeast two-hybrid screen, several methods are used to validate the initial result before carrying out functional experiments. Nowadays, non-invasive fluorescence-based methods like Bioluminescence Resonance Energy Transfer (BRET) and Fluorescence Resonance Energy Transfer (FRET) are widely used in the study of protein-protein interactions in living cells. In the present review, we address the individual strengths and weaknesses of both RET approaches, providing information on their possible future use in the study of G protein-coupled receptor oligomerization. C1 [Gandia, Jorge; Ciruela, Francisco] Univ Barcelona, Fac Med, Dept Patol & Terapeut Expt, Unitat Farmacol, E-08007 Barcelona, Spain. [Lluis, Carme; Franco, Rafael] Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, E-08007 Barcelona, Spain. [Lluis, Carme; Franco, Rafael] Univ Barcelona, Fac Biol, Inst Invest Biomed August Pi & Sunyer, E-08007 Barcelona, Spain. [Ferre, Sergi] Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD USA. RP Ciruela, F (reprint author), Hosp Llobregat, Fac Med, Dept Patol & Terapeut Expt, Unitat Farmacol, Campus Bellvitge,Av Feixa Llarga S-N, Barcelona 08907, Spain. EM fciruela@ub.edu RI Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Gandia, Jorge/P-3373-2016 OI Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Gandia, Jorge/0000-0003-1711-8075 NR 38 TC 28 Z9 30 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2008 VL 30 IS 1 BP 82 EP 89 DI 10.1002/bies.20682 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 250XM UT WOS:000252334600011 PM 18081019 ER PT J AU Xu, XJ Zhao, YD Simon, R AF Xu, Xiaojiang Zhao, Yingdong Simon, Richard TI Gene Set Expression Comparison kit for BRB-ArrayTools SO BIOINFORMATICS LA English DT Article ID SEQUENCES; KNOWLEDGE; PROFILES; TOOLS; P53 AB A Gene Set Expression Comparison kit is developed as a module of BRB-ArrayTools for discovering biologically meaningful patterns in gene expression data. The kit consists of gene sets of transcription factor (TF) targets, gene sets containing genes whose protein products share the same protein domain and gene sets of microRNA targets. Using this module of BRB-ArrayTools, researchers can efficiently analyze pre-defined sets of gene whose expression is correlated with a categorical quantitative phenotype or patient survival. Supplementary information: Supplementary data are available at Bioinformatics online. C1 [Xu, Xiaojiang; Zhao, Yingdong; Simon, Richard] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 38 Z9 38 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN 1 PY 2008 VL 24 IS 1 BP 137 EP 139 DI 10.1093/bioinformatics/btm541 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 244KO UT WOS:000251865000021 PM 18006549 ER PT S AU Zaslavsky, L Tatusova, TA AF Zaslavsky, Leonid Tatusova, Tatiana A. BE Mandoiu, I Sunderraman, R Zelikovsky, A TI Accelerating the neighbor-joining algorithm using the adaptive bucket data structure SO BIOINFORMATICS RESEARCH AND APPLICATIONS SE LECTURE NOTES IN BIOINFORMATICS LA English DT Proceedings Paper CT 4th International Symposium on Bioinformatics Research and Applications CY MAY 06-09, 2008 CL Georgia State Univ, Atlanta, GA HO Georgia State Univ DE neighbor-joining algorithm; bucket data structure; adaptive; cache-efficient ID RECONSTRUCTION; PERFORMANCE AB The complexity of the neighbor joining method is determined by the complexity of the search for an optimal pair ("neighbors to join") performed globally at each iteration. Accelerating the neighborjoining method requires performing a smarter search for an optimal pair of neighbors, avoiding re-evaluation of all possible pairs of points at each iteration. We developed an acceleration technique for the neighbor-joining method that significantly decreases complexity for important applications without any change in the neighbor-joining method. This technique utilizes the bucket data structure. The pairs of nodes are arranged in buckets according to values of the goal function delta(ij) = u(i) + u(j) - d(ij). Buckets are adaptively re-arranged after each neighbor-joining step. While the pairs of nodes in the top bucket are re-evaluated at every iteration, pairs in lower buckets are accessed more rarely, when the algorithm determines that the elements of the bucket need to be re-evaluated based on new values of delta(ij). As a result, only a small portion of candidate pairs of nodes is examined at each iteration. The algorithm is cache efficient, since the bucket data structures are able to exploit locality and adjust to cache properties. C1 [Zaslavsky, Leonid; Tatusova, Tatiana A.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Zaslavsky, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 29 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-79449-3 J9 LECT N BIOINFORMAT PY 2008 VL 4983 BP 122 EP 133 PG 12 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BHS35 UT WOS:000255941000011 ER PT S AU Zeng, XQ Li, GZ Yang, JY Yang, MQ AF Zeng, Xue-Qiang Li, Guo-Zheng Yang, Jack Y. Yang, Mary Qu BE Mandoiu, I Sunderraman, R Zelikovsky, A TI A novel metric for redundant gene elimination based on discriminative contribution SO BIOINFORMATICS RESEARCH AND APPLICATIONS SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 4th International Symposium on Bioinformatics Research and Applications CY MAY 06-09, 2008 CL Georgia State Univ, Atlanta, GA HO Georgia State Univ ID FEATURE-SELECTION; CLASSIFICATION; MICROARRAY; RELEVANCE; PATTERNS; CANCER AB As a high dimensional problem, analysis of microarray data sets is a hard task, where many weakly relevant but redundant features hurt generalization performance of classifiers. There are previous works to handle this problem by using linear or nonlinear filters, but these filters do not consider discriminative contribution of each feature by utilizing the label information. Here we propose a novel metric based on discriminative contribution to perform redundant feature elimination. By the new metric, complementary features are likely to be reserved, which is beneficial for the final classification. Experimental results on several microarray data sets show our proposed metric for redundant feature elimination based on discriminative contribution is better than the previous state-of-arts linear or nonlinear metrics on the problem of analysis of microarray data sets. C1 [Zeng, Xue-Qiang; Li, Guo-Zheng] Shanghai Univ, Inst Syst Biol, Shanghai 200444, Peoples R China. [Zeng, Xue-Qiang; Li, Guo-Zheng] Shanghai Univ, Sch Engn & Comp Sci, Shanghai 200072, Peoples R China. [Yang, Mary Qu] NIH, NHGRI, US Dept HHS, Rockville, MD 20852 USA. RP Li, GZ (reprint author), Shanghai Univ, Inst Syst Biol, Shanghai 200444, Peoples R China. EM gzli@shu.edu.cn FU Natural Science Foundation of China [20503015]; STCSM "Innovation Action Plan" Project of China [07DZ19726]; Shanghai Leading Academic Discipline Project [J50103]; Systems Biology Research Foundation of Shanghai University; Scientific Research Fund of Jiangxi Provincial Education Departments [2007-57] FX This work was supported in part by the Natural Science Foundation of China under grant no. 20503015, the STCSM Innovation Action Plan Project of China under grant no. 07DZ19726, Shanghai Leading Academic Discipline Project under no. J50103, Systems Biology Research Foundation of Shanghai University and Scientific Research Fund of Jiangxi Provincial Education Departments under grant no. 2007-57. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-79449-3 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2008 VL 4983 BP 256 EP + PG 3 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BHS35 UT WOS:000255941000023 ER PT S AU Buetow, K AF Buetow, Kenneth BE Mandoiu, I Sunderraman, R Zelikovsky, A TI Invited keynote talk: Quiet revolution: Connectivity in the cancer research community SO BIOINFORMATICS RESEARCH AND APPLICATIONS SE LECTURE NOTES IN BIOINFORMATICS LA English DT Proceedings Paper CT 4th International Symposium on Bioinformatics Research and Applications CY MAY 06-09, 2008 CL Georgia State Univ, Atlanta, GA HO Georgia State Univ C1 NCI, Ctr Bioinformat, Rockville, MD USA. RP Buetow, K (reprint author), NCI, Ctr Bioinformat, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-79449-3 J9 LECT N BIOINFORMAT PY 2008 VL 4983 BP 280 EP 280 PG 1 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BHS35 UT WOS:000255941000025 ER PT S AU Berezkovskii, AM AF Berezkovskii, Alexander M. BE Dagdug, L Scherer, LGC TI Diffusion-controlled reaction with a spot on the side wall of a cylinder membrane channel SO BIOLOGICAL PHYSICS SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 3rd Mexican Meeting on Mathematical and Experimental Physics CY SEP 10-14, 2007 CL Colegio Nacl, Mexico City, MEXICO SP Univ Autonoma Metropolitana, CONACyT, CINVESTAV IPN HO Colegio Nacl DE diffusion; membrane channel; binding site ID PARTICLE NUMBER FLUCTUATIONS; ION-CHANNEL; TRANSPORT; BINDING; DYNAMICS; KINETICS; ESCAPE; SITE AB We develop a theory of diffusion-controlled reactions with a spot located on the sidewall of a cylindrical membrane channel that connects two reservoirs containing diffusing particles which are trapped by the site at the first contact. An expression for the Laplace transform of the rate coefficient k(t) is derived assuming that the size of the site is small compared to the channel radius. The expression is used to find the stationary value of the rate coefficient k(infinity), as a function of the length and radius of the channel, the radius of the site and its position inside the channel as well as the particle diffusion constants in the bulk and in the channel. Our derivation is based on the one-dimensional description of the particle motion in the channel including a binding site. The validity of the approximate one-dimensional description of diffusion was checked by three-dimensional Brownian dynamics simulations. We found that the one-dimensional description works reasonably well when the size of the site does not exceed 0.2 of the channel radius. C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Berezkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0497-7 J9 AIP CONF PROC PY 2008 VL 978 BP 11 EP 33 PG 23 WC Biophysics; Mathematics, Applied; Physics, Applied SC Biophysics; Mathematics; Physics GA BHJ40 UT WOS:000253559400002 ER PT J AU Diaz-Asper, CM Goldberg, TE Kolachana, BS Straub, RE Egan, MF Weinberger, DR AF Diaz-Asper, Catherine M. Goldberg, Terry E. Kolachana, Bhaskar S. Straub, Richard E. Egan, Michael F. Weinberger, Daniel R. TI Genetic variation in catechol-O-methyltransferase: Effects on working memory in schizophrenic patients, their siblings, and healthy controls SO BIOLOGICAL PSYCHIATRY LA English DT Article DE attention; catechol-O-methyltransferase; COMT; prefrontal cognition; schizophrenia; working memory ID COMT GENE; HUMAN BRAIN; FUNCTIONAL POLYMORPHISM; ENZYME-ACTIVITY; RELATIVE RISK; MET GENOTYPE; ASSOCIATION; COGNITION; DOPAMINE; ATTENTION AB Background: Catechol-O-methyltransferase (COMT) val(108/158) met (rs4680) is thought to affect dopamine regulated prefrontal cortical activity during working memory (WM) tasks, and to weakly increase risk for developing schizophrenia. Recently, other single nucleotide polymorphisms (SNPs) across the gene have emerged as additional risk factors for schizophrenia: namely rs737865, rs165599, and rs2097603. In a large sample, we examined whether these SNPs affect WM. Methods: Schizophrenic probands (n = 325), their nonpsychotic siblings (n = 359), and normal control subjects (n = 330) completed tests of WM function. Data were analyzed with a series of mixed model analyses of variance (ANOVAs). Results: Val homozygotes performed most poorly on all conditions of the n-back, irrespective of diagnosis. Additionally, there was a trend towards a disease-only val(108/158) met effect on a test of attentional set-shifting; val homozygote probands performed most poorly. Significant or near-significant effects of rs737865 were found on all conditions of the n-back, with G homozygotes performing worst. There also was a disease-only COMT rs737865 effect on the 0-back. None of the other SNPs showed main effects by themselves. A haplotype constructed from promoter and val(108/158)met SNPs showed main effects on WM parameters, consistent with inverted U models of doparmine signaling. Conclusions: We extended earlier findings of a val(108/158)met effect on WM function, and suggest that combinations of alleles within COMT may modulate the val(108/158). met effect in a nonlinear manner. C1 [Goldberg, Terry E.] Zucker Hillside Hosp, Albert Einstein Coll Med, Div Psychiat Res, Glen Oaks, NY 11004 USA. [Diaz-Asper, Catherine M.; Goldberg, Terry E.; Kolachana, Bhaskar S.; Straub, Richard E.; Egan, Michael F.; Weinberger, Daniel R.] NIMH, Natl Inst Hlth, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Goldberg, TE (reprint author), Zucker Hillside Hosp, Albert Einstein Coll Med, Div Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM Tgoldber@NSHS.edu FU NIMH NIH HHS [P50 MH080173] NR 52 TC 79 Z9 80 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2008 VL 63 IS 1 BP 72 EP 79 DI 10.1016/j.biopsych.2007.03.031 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 244KE UT WOS:000251864000012 PM 17707347 ER PT J AU Goldberg, TE Iudicello, J Russo, C Elvevag, B Straub, R Egan, MF Weinberger, DR AF Goldberg, Terry E. Iudicello, Jennifer Russo, Christine Elvevag, Brita Straub, Richard Egan, Michael F. Weinberger, Daniel R. TI BDNF Val(66) Met polymorphism significantly affects d ' in verbal recognition memory at short and long delays SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE BDNF; memory; cognition; genetics; encoding ID ACTIVITY-DEPENDENT SECRETION; FACTOR VAL66MET POLYMORPHISM; EPISODIC MEMORY; TERM POTENTIATION; FALSE MEMORIES; SCHIZOPHRENIA; HIPPOCAMPUS; ASSOCIATION; PERFORMANCE; INDUCTION AB A functional polymorphism at the val66met locus in the BDNF gene has significant effects on the pro-form of the protein in intracellular trafficking and activity-dependent, but not constitutive, secretion. These differences are thought to underlie several findings in humans related to this polymorphism, including markers of neuronal viability, BOLD activation in medial temporal Job regions, and some aspects of behavior. However, many important questions remain about the impact of BDNF on various mnemonic subprocesses at the behavioral level. In this study, we examined the impact of the val/met polymorphism in a verbal recognition memory paradigm involving manipulation of depth of encoding and differential delays for recall and analyses of hits for previously presented target words and correct rejections of foils. Twenty-four human val homozygous individuals and 24 met carrier individuals comprised the sample. All were healthy controls. IQ between the groups was equivalent. In the encoding phase of the study, words were presented and encoded either by a decision as to whether they were living or nonliving ("deep") or if they contained the letter "A" (shallow). After this phase, recognition was tested immediately, half an hour, and 24 It later. BDNF genotype had significant effects on hits and discriminability (d'), accounting for at least 10% of the variance, but not on correct rejections or beta. BDNF did not interact with level of encoding, nor did it interact with delay. In sum, BDNF genotypes impacted "hits" in a recognition memory paradigm, findings consistent with the general notion that BDNF plays a prominent role in memory subprocesses thought to engage the medial temporal lobe. (C) 2007 Published by Elsevier B.V. C1 [Goldberg, Terry E.; Iudicello, Jennifer; Russo, Christine; Elvevag, Brita; Straub, Richard; Egan, Michael F.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders, Bethesda, MD 20892 USA. [Goldberg, Terry E.] N Shore Long Island Jewish Hlth Syst, Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY 11004 USA. RP Goldberg, TE (reprint author), NIMH, Clin Brain Disorders, Bethesda, MD 20892 USA. EM tgoldberg@nshs.edu NR 27 TC 47 Z9 49 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JAN PY 2008 VL 77 IS 1 BP 20 EP 24 DI 10.1016/j.biopsycho.2007.08.009 PG 5 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 256YS UT WOS:000252766400003 PM 17988784 ER PT J AU Tomer, R Goldstein, RZ Wang, GJ Wong, C Volkow, ND AF Tomer, Rachel Goldstein, Rita Z. Wang, Gene-Jack Wong, Christopher Volkow, Nora D. TI Incentive motivation is associated with striatal dopamine asymmetry SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE dopamine; asymmetry; motivation; striatum ID POSITRON-EMISSION-TOMOGRAPHY; BASAL GANGLIA; PARKINSONS-DISEASE; PERSONALITY; RECEPTORS; CIRCUITS; BEHAVIOR; BINDING; CORTEX; BRAIN AB Dopamine plays an important role in modulating incentive motivation, expressed behaviorally as approach behavior. EEG studies report association between approach behavior and asymmetric pattern of activation in anterior cortical regions (as measured by the inverse of EEG alpha power). Therefore. individual differences in incentive motivation may reflect asymmetries in dopaminergic systems. We examined this hypothesis by studying the relationship between self-reported degree of incentive motivation, and asymmetry of D2 receptor availability in healthy volunteers. Nineteen healthy participants were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors in left and right striatum. Incentive motivation was assessed by the Achievement scale of the Multidimensional Personality Questionnaire. The Achievement score was negatively correlated with the Asymmetry Index ([R - L]/[R + L]) of D2 receptor availability (r = -.721, p = .001), suggesting that greater positive incentive motivation is associated with higher receptor availability in the left relative to the right hemisphere. (C) 2007 Elsevier B.V. All fights reserved. C1 [Tomer, Rachel] Univ Haifa, Dept Psychol, IL-31905 Haifa, Israel. [Goldstein, Rita Z.; Wang, Gene-Jack; Wong, Christopher] Univ Haifa, Brain & Behav Ctr, IL-31905 Haifa, Israel. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA. RP Tomer, R (reprint author), Univ Haifa, Dept Psychol, Mt Carmel, IL-31905 Haifa, Israel. EM rtomer@psy.haifa.ac.il RI tomer, rachel/E-5747-2013 FU NIAAA NIH HHS [R01 AA009481-09]; NIDA NIH HHS [K23 DA015517, K23 DA015517-05, R01 DA006891-10, R01 DA023579] NR 22 TC 55 Z9 55 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JAN PY 2008 VL 77 IS 1 BP 98 EP 101 DI 10.1016/j.biopsycho.2007.08.001 PG 4 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 256YS UT WOS:000252766400015 PM 17868972 ER PT J AU Kurnat-Thoma, EL AF Kurnat-Thoma, Emma L. TI Hereditary nonpolyposis colorectal cancer (Lynch syndrome): Molecular pathogenesis and clinical approaches to diagnosis and management for nurses SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Article DE HNPCC; Lynch syndrome; review; nursing; pathogenesis; screening; microsatellite instability (MSI); mismatch repair (MMR); family history; colorectal cancer ID DNA MISMATCH-REPAIR; REVISED BETHESDA GUIDELINES; PRIMARY-CARE PHYSICIANS; MICROSATELLITE INSTABILITY; COLON-CANCER; GERMLINE MUTATIONS; UNITED-STATES; GENE DEFECTS; IMMUNOHISTOCHEMISTRY; HNPCC AB Hereditary nonpolyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is the most common form of hereditary colorectal cancer and is responsible for 2% to 4% of all colorectal cancers in the Western hemisphere. Generally characterized by early-onset colorectal carcinoma with a mean age of presentation of 40 to 45 years, it can also manifest with extracolonic adenocarcinomas and cancers of the endometrium, ovaries, stomach, pancreas, small intestine, hepatobiliary tract, upper uroepithelial tract, brain, and skin. HNPCC is autosomal dominant and carries an 80% lifetime risk of cancer development. This review addresses the molecular underpinnings of HNPCC while providing a concise approach to clinical detection, diagnosis, and management of patients who may or may not test positive for an HNPCC-causing mutation. Although applicable to any patient-care setting in which cancer may be observed, this review specifically addresses the role of nurses in detecting, diagnosing, and clinically managing HNPCC. C1 [Kurnat-Thoma, Emma L.] Univ Utah, Grad Partnership Program Scholar, NINR, Natl Inst Hlth, Salt Lake City, UT USA. RP Kurnat-Thoma, EL (reprint author), Louis B Strokes Lab, Rm 5305 MSC 8004,50 S Dr, Bethesda, MD 20892 USA. EM kurnate@mail.nih.gov FU Intramural NIH HHS NR 66 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 J9 BIOL RES NURS JI Biol. Res. Nurs. PD JAN PY 2008 VL 9 IS 3 BP 185 EP 199 DI 10.1177/1099800407308558 PG 15 WC Nursing SC Nursing GA 242PG UT WOS:000251737100001 PM 18077771 ER PT J AU Kurnat-Thoma, EL AF Kurnat-Thoma, Emma L. TI Hereditary nonpolyposis cancer (Lynch syndrome): Response to commentary SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Editorial Material C1 [Kurnat-Thoma, Emma L.] NHGRI, Grad Partnership Program, NINR, NIH, Bethesda, MD 20892 USA. RP Kurnat-Thoma, EL (reprint author), NHGRI, Louis B Stokes Lab, Rm 5305 MSC 8004,50 S Drive, Bethesda, MD 20892 USA. EM kurnate@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 J9 BIOL RES NURS JI Biol. Res. Nurs. PD JAN PY 2008 VL 9 IS 3 BP 203 EP 204 DI 10.1177/1099800407309220 PG 2 WC Nursing SC Nursing GA 242PG UT WOS:000251737100003 ER PT J AU Teshima, T Wynn, TA Soiffer, RJ Matsuoka, KI Martin, PJ AF Teshima, Takanori Wynn, Thomas A. Soiffer, Robert J. Matsuoka, Ken-Ichi Martin, Paul J. TI Chronic graft-versus-host disease: How can we release Prometheus? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article C1 [Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Teshima, Takanori] Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. [Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH,DHHS, Bethesda, MD 20892 USA. [Soiffer, Robert J.; Matsuoka, Ken-Ichi] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Martin, PJ (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,1100 Fairview Ave N,D2-100, Seattle, WA 98109 USA. EM pmartin@fhcrc.org RI Wynn, Thomas/C-2797-2011; teshima, takanori/G-1671-2012; OI teshima, takanori/0000-0002-0941-271X NR 0 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2008 VL 14 IS 1 BP 142 EP + DI 10.1016/j.bbmt.2007.10.023 PG 3 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 250XB UT WOS:000252333500032 PM 18162235 ER PT J AU Jayes, F Rodriguez, K Couse, J Yates, M Korach, K AF Jayes, Friederike Rodriguez, Karina Couse, John Yates, Mariana Korach, Kenneth TI Estrogen receptor-beta action in the ovary, but not in the hypothalamic-pituitary axis, is required for the generation of normal luteinizing hormone surges in mice SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 [Jayes, Friederike; Rodriguez, Karina; Couse, John; Yates, Mariana; Korach, Kenneth] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 6 BP 52 EP 52 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300007 ER PT J AU Hu, W Gauthier, L Baibakov, B Dean, J AF Hu, Wei Gauthier, Lyn Baibakov, Boris Dean, Jurrien TI Ectopic expression of FIGLA in male germ cells represses testis-specific genes and disrupts fertility in transgenic mice SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 [Hu, Wei; Gauthier, Lyn; Baibakov, Boris; Dean, Jurrien] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 33 BP 59 EP 59 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300034 ER PT J AU Jefferson, W Padilla-Banks, E Goulding, E Williams, C Newbold, R AF Jefferson, Wendy Padilla-Banks, Elizabeth Goulding, Eugenia Williams, Carmen Newbold, Retha TI Neonatal exposure to genistein adversely affects MouseOocyte developmental competence SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 [Jefferson, Wendy; Padilla-Banks, Elizabeth; Goulding, Eugenia; Williams, Carmen; Newbold, Retha] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 135 BP 84 EP 84 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300126 ER PT J AU Zheng, P Dean, J AF Zheng, Ping Dean, Jurrien TI Filia, a maternal effect gene that regulates cleavage embryogenesis in mice SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 [Zheng, Ping; Dean, Jurrien] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 183 BP 95 EP 95 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300170 ER PT J AU Nakamura, N Dai, QS Eddy, M AF Nakamura, Noriko Dai, Qunsheng Eddy, Mitch TI A novel mouse enolase 1-like gene is expressed specifically in spermatogenic cells and encodes a protein present in the principal piece region of the sperm flagellum SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 [Nakamura, Noriko; Dai, Qunsheng; Eddy, Mitch] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 231 BP 107 EP 107 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300214 ER PT J AU Li, L Baibakov, B Dean, J AF Li, Lei Baibakov, Boris Dean, Jurrien TI Maternally encoded FLOPED complex required for early cleavage stage of mouse embryogenesis SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kailua Kona, HI SP Soc Study Reprod C1 [Li, Lei; Baibakov, Boris; Dean, Jurrien] NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 292 BP 122 EP 122 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300272 ER PT J AU Gahlay, G Dean, J AF Gahlay, Gagandeep Dean, Jurrien TI The cleavage status of ZP2 determines initial sperm-egg recognition in mice SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 [Gahlay, Gagandeep; Dean, Jurrien] NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 355 BP 138 EP 138 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300333 ER PT J AU Hines, E Kato, K Kuklenyik, Z VonEhrenstein, O Calafat, A Fenton, S AF Hines, Erin Kato, Kayoko Kuklenyik, Zsuzsanna VonEhrenstein, Ondine Calafat, Antonia Fenton, Suzanne TI Concentrations of perfluoroalkyl compounds in the serum and milk of lactating North Carolina women SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 US EPA, RTD, DBB, Res Triangle Pk, NC 27711 USA. CDC, DLS, NCEH, Atlanta, GA 30333 USA. NICHHD, CDC, SPR, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 467 BP 164 EP 164 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300436 ER PT J AU Ochoa, MIH Ringgold, K Leslie, T Gupta, R Flaws, J AF Ochoa, Maria Isabel Hernandez Ringgold, Kimberly Leslie, Traci Gupta, Rupesh Flaws, Jodi TI The ability of the aryl hydrocarbon receptor to regulate steroidogenesis may depend on sexual maturity in mice SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 Univ Illinois, Urbana, IL 61801 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 524 BP 178 EP 178 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300485 ER PT J AU Kokkinaki, M Lee, TL Golestaneh, N He, ZP Jiang, JJ Chan, WY Dym, M AF Kokkinaki, Maria Lee, Tin-Lap Golestaneh, Nady He, Zuping Jiang, Jiji Chan, Wai Yee Dym, Martin TI Gene expression analysis in spermatogonial stem cells from 6-day-, 21-day-, and 60-day-old mice SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kailua Kona, HI SP Soc Study Reprod C1 Georgetown Univ, Washington, DC USA. NICHHD, NIH, Bethesda, MD 20892 USA. RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 556 BP 185 EP 185 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300513 ER PT J AU Odet, F Duan, CW Willis, W Goulding, E Kung, A Eddy, M Goldberg, E AF Odet, Fanny Duan, Chongwen Willis, William Goulding, Eugenia Kung, Aisha Eddy, Mitch Goldberg, Erwin TI Lactate dehydrogenase-C-4 (LDH-C-4) is essential for sperm function SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Northwestern Univ, Evanston, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 567 BP 187 EP 187 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300523 ER PT J AU Geyer, C Inselman, A Sunman, J Bornstein, S Handel, M Eddy, M AF Geyer, Chris Inselman, Amy Sunman, Jeff Bornstein, Sheila Handel, Mary Eddy, Mitch TI A missense mutation is present in the Capza3 gene of ENC-generated repro32 male infertility mutants SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 [Geyer, Chris; Inselman, Amy; Sunman, Jeff; Bornstein, Sheila; Handel, Mary; Eddy, Mitch] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 603 BP 196 EP 196 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300559 ER PT J AU Zhang, Y Lin, L Cao, Y Chen, B Ge, R AF Zhang, Yunhui Lin, Ling Cao, Yang Chen, Bingheng Ge, Renshan TI Maternal exposure of phthalates in low-birth-weight newborns: A case-control study in Shanghai, China SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 Populat Council, New York, NY 10021 USA. Fudan Univ, Shanghai 200433, Peoples R China. NIEHS, Res Triangle Pk, NC 27709 USA. RI Cao, Yang/C-6185-2008 OI Cao, Yang/0000-0002-3552-9153 NR 0 TC 0 Z9 0 U1 0 U2 6 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 614 BP 198 EP 199 PG 2 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300570 ER PT J AU Haga, Y Nakamura, N Matsuno, Y Eddy, EM Mori, C AF Haga, Yosuke Nakamura, Noriko Matsuno, Yoshiharu Eddy, E. Mitch Mori, Chisato TI Expression levels of transcripts for spermatogenic cell-specific glycolytic enzymes (HK1S, GAPDHS and PGK2) in juvenile mice assayed using RNA isolated from germ cells by laser capture microdissection SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 Chiba Univ, Chiba, Japan. Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 747 BP 230 EP 230 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300688 ER PT J AU Armant, D Jessmon, P Petkova, A Romero, R Leach, R AF Armant, D. Jessmon, Philip Petkova, Anelia Romero, Roberto Leach, Richard TI Post-transcriptional regulation of a factor required for survival at low oxygen concentrations by human first-trimester cytotrophoblast cells SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT World Congress on Reproductive Biology CY MAY 24-25, 2008 CL Kailua Kona, HI C1 Wayne State Univ, Detroit, MI USA. NICHD, NIH, Bethesda, MD USA. Michigan State Univ, Grand Rapids, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 98 BP 307 EP 307 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300846 ER PT S AU Cantor, D AF Cantor, David BE Hannaway, C TI Radium and the Origins of the National Cancer Institute SO BIOMEDICINE IN THE TWENTIETH CENTURY: PRACTICES, POLICIES, AND POLITICS SE Biomedical and Health Research LA English DT Article; Book Chapter C1 [Cantor, David] Natl Lib Med, Bethesda, MD USA. [Cantor, David] NCI, Bethesda, MD 20892 USA. RP Cantor, D (reprint author), Natl Lib Med, Bethesda, MD USA. NR 217 TC 4 Z9 4 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0929-6743 BN 978-1-58603-832-8 J9 BIOMED HEALTH RES JI Biom. Health Res. PY 2008 VL 72 BP 95 EP 146 PG 52 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA BMB29 UT WOS:000271731200005 ER PT J AU Xie, YL Deng, SX Thomas, CJ Liu, YD Zhang, YQ Rinderspacher, A Huang, WW Gong, GL Wyler, M Cayanis, E Aulner, N Tobben, U Chung, C Pampou, S Southall, N Vidovic, D Schurer, S Branden, L Davis, RE Staudt, LM Inglese, J Austin, CP Landry, DW Smith, DH Auld, DS AF Xie, Yuli Deng, ShiXian Thomas, Craig J. Liu, Yidong Zhang, Ya-Qin Rinderspacher, Alison Huang, Wenwei Gong, Gangli Wyler, Michael Cayanis, Efithia Aulner, Nathalie Toebben, Udo Chung, Caty Pampou, Sergey Southall, Noel Vidovic, Dusica Schuerer, Stephan Branden, Lars Davis, R. Eric Staudt, Louis M. Inglese, James Austin, Christopher P. Landry, Donald W. Smith, Deborah H. Auld, Douglas S. TI Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-regulating NF kappa B activity within two separate high-throughput screens of NF kappa B activation SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID IN-VIVO; INHIBITORS; EXPRESSION; PATHWAYS; CELLS AB We describe here a series of N-(quinolin-8-yl)benzenesulfonamides capable of suppressing the NF kappa B pathway identified from two high-throughput screens run at two centers of the NIH Molecular Libraries Initiative. These small molecules were confirmed in both primary and secondary assays of NF kappa B activation and expanded upon through analogue synthesis. The series exhibited potencies in the cell-based assays at as low as 0.6 mu M, and several indications suggest that the targeted activity lies within a common region of the NF kappa B pathway. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Xie, Yuli; Deng, ShiXian; Liu, Yidong; Rinderspacher, Alison; Gong, Gangli; Landry, Donald W.] Columbia Univ, Dept Med, Div Clin Pharmacol & Expt Therapeut, New York, NY 10032 USA. [Thomas, Craig J.; Zhang, Ya-Qin; Huang, Wenwei; Southall, Noel; Inglese, James; Austin, Christopher P.; Smith, Deborah H.; Auld, Douglas S.] NHGRI, NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. [Wyler, Michael; Cayanis, Efithia; Aulner, Nathalie; Toebben, Udo; Pampou, Sergey; Branden, Lars; Smith, Deborah H.] Columbia Univ, Columbia Genome Ctr, MLSCN Ctr, New York, NY 10032 USA. [Chung, Caty; Vidovic, Dusica; Schuerer, Stephan] Scripps Res Inst, Jupiter, FL 33458 USA. [Davis, R. Eric; Staudt, Louis M.] NCI, NIH, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. RP Landry, DW (reprint author), Columbia Univ, Dept Med, Div Clin Pharmacol & Expt Therapeut, 630 W 168th St, New York, NY 10032 USA. EM dwll@columbia.edu; dauld@mail.nih.gov RI Southall, Noel/H-8991-2012; OI Southall, Noel/0000-0003-4500-880X; Branden, Lars/0000-0002-1904-0470 FU Intramural NIH HHS [, NIH0011934955]; PHS HHS [NIH0011934955] NR 24 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 1 PY 2008 VL 18 IS 1 BP 329 EP 335 DI 10.1016/j.bmcl.2007.10.100 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 270KS UT WOS:000253720300060 PM 18024113 ER PT J AU Zheng, JY Tsai, YC Kadimcherla, P Zhang, R Shi, J Oyler, GA Boustany, NN AF Zheng, Jing-Yi Tsai, Yien-Che Kadimcherla, Pradeep Zhang, Rong Shi, Julia Oyler, George A. Boustany, Nada N. TI The C-terminal transmembrane domain of Bcl-x(L) mediates changes in mitochondrial morphology SO BIOPHYSICAL JOURNAL LA English DT Article ID BCL-X-L; NUCLEOTIDE-INDUCED CONTRACTION; RAT-LIVER MITOCHONDRIA; CYTOCHROME-C; LIGHT-SCATTERING; MATRIX VOLUME; CELL-DEATH; OXIDATIVE-STRESS; PEPTIDE COMPLEX; BONGKREKIC ACID AB We investigate the effect of mitochondrial localization and the Bcl-x(L) C-terminal transmembrane (TM) domain on mitochondrial morphology and subcellular light scattering. CSM 14.1 cell lines stably expressed yellow fluorescent protein (YFP), YFP-Bcl-x(L), YFP-Bcl-x(L)-Delta TM, containing the remainder of Bcl-xL after deletion of the last 21 amino acids corresponding to the TM domain, or YFP-TM, consisting of YFP fused at its C-terminal to the last 21 amino acids of Bcl-x(L). YFP-Bcl-x(L) and YFP-TM localized to the mitochondria. Their expression decreased the intensity ratio of wide-to-narrow angle forward scatter by subcellular organelles, and correlated with an increase in the proportion of mitochondria with an expanded matrix having greatly reduced intracristal spaces as observed by electron microscopy. Cells expressing YFP-TM also exhibited significant autophagy. In contrast, YFP-Bcl-x(L)-Delta TM was diffusely distributed in the cells, and its expression did not alter light scattering or mitochondrial morphology compared with parental cells. Expression of YFP-Bcl-x(L) or YFP-Bcl-x(L)-Delta TM provided significant resistance to staurosporine-induced apoptosis. Surprisingly however, YFP-TM expression also conferred a moderate level of cell death resistance in response to staurosporine. Taken together, our results suggest the existence of a secondary Bcl-x(L) function that is mediated by the transmembrane domain, alters mitochondrial morphology, and is distinct from BH3 domain sequestration. C1 [Zheng, Jing-Yi; Kadimcherla, Pradeep; Boustany, Nada N.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. [Tsai, Yien-Che] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. [Zhang, Rong] Univ Florida, Dept Comp & Informat Sci & Engn, Gainesville, FL USA. [Shi, Julia] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Oyler, George A.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA. RP Boustany, NN (reprint author), Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. EM nboustan@rci.rutgers.edu OI Tsai, Yien Che/0000-0001-9624-1092 FU NCRR NIH HHS [R21RR015264] NR 68 TC 17 Z9 17 U1 1 U2 1 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 1 PY 2008 VL 94 IS 1 BP 286 EP 297 DI 10.1529/biophysj.107.104323 PG 12 WC Biophysics SC Biophysics GA 240VH UT WOS:000251615800033 PM 17766334 ER PT S AU Boukari, H Sackett, DL AF Boukari, Hacene Sackett, Dan L. BE Correia, JJ Detrich, HW TI Fluorescence correlation Spectroscopy and its application to the characterization of molecular properties and interactions SO BIOPHYSICAL TOOLS FOR BIOLOGISTS: VOL 1 IN VITRO TECHNIQUES SE Methods in Cell Biology LA English DT Review; Book Chapter ID CROSS-CORRELATION SPECTROSCOPY; PHOTON-COUNTING HISTOGRAM; FLUCTUATION SPECTROSCOPY; LIVING CELLS; DIFFUSION; PROTEINS; PARTICLES; DYNAMICS; BINDING; PROBE AB Fluorescence correlation spectroscopy (FCS) utilizes temporal fluctuations in fluorescence emission to extract quantitative measures of inter- or intramolecular dynamics or molecular motions of probe molecules, which occur on submicrosecond to second timescales. In typical experiments, one can readily obtain the probe's diffusion coefficient and concentration from small volumes of sample. Recent FCS applications have yielded information on interactions of the probe with changing or structured solvent, binding with other molecules, photophysical or conformational changes in the probe, polymerization, and other changes in the dynamics of the probe. In cross-correlation mode FCS promises to attract more applications as the technique can monitor interactions in a system with two or more probes with different fluorophores. C1 NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Boukari, H (reprint author), NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 39 TC 6 Z9 6 U1 0 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-372520-2 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2008 VL 84 BP 659 EP 678 DI 10.1016/S0091-679X(07)84021-0 PG 20 WC Cell Biology SC Cell Biology GA BGX35 UT WOS:000251127600021 PM 17964946 ER PT J AU Ireland, DC Wang, CKL Wilson, JA Gustafson, KR Craik, DJ AF Ireland, David C. Wang, Conan K. L. Wilson, Jennifer A. Gustafson, Kirk R. Craik, David J. TI Cyclotides as natural anti-HIV agents SO BIOPOLYMERS LA English DT Article DE circular proteins; cyclic cystine knot; HIV ID INHIBITORY MACROCYCLIC PEPTIDES; POLYPEPTIDE KALATA B1; CYCLIC CYSTINE KNOT; CIRCULAR PROTEINS; PLANT CYCLOTIDES; MOMORDICA-COCHINCHINENSIS; 3-DIMENSIONAL STRUCTURE; ANTIMICROBIAL PEPTIDES; CHASSALIA-PARVIFOLIA; OLDENLANDIA-AFFINIS AB Cyclotides are disulfide rich macrocyclic plant peptides that are defined by their unique topology in which a head-to-tail cyclized backbone is knotted by the interlocking arrangement of three disulfide bonds. This cyclic cystine knot motif gives the cyclotides exceptional resistance to thermal, chemical, or enzymatic degradation. Over 100 cyclotides have been reported and display a variety of biological activities, including a cytoprotective effect against HIV infected cells. It has been hypothesized that cyclotides from one subfamily, the Mobius subfamily, may be more appropriate than bracelet cyclotides as drug candidates given their lower toxicity to uninfected cells. Here, we report the anti-HIV and cytotoxic effects of three cyclotides, including two from the Mobius subfamily. We show that Mobius cyclotides have comparable inhibitory activity against HIV infection to bracelet cyclotides and that they are generally less cytotoxic to the target cells. To explore the structure activity relationships (SARs) of the 29 cyclotides tested so far for anti-HIV activity, we modeled the structures of the 21 cyclotides whose structures have not been previously solved. We show that within cyclotide subfamilies there is a correlation between hydrophobicity of certain loop regions and HIV inhibition. We also show that charged residues in these loops impact on the activity of the cyclotides, presumably by modulating membrane binding. In addition to providing new SAR data, this report is a mini-review that collates all cyclotide anti-HIV information reported so far and provides a resource for future studies on the therapeutic potential of cyclotides as natural anti-HIVagents. (C) 2007 Wiley Periodicals, Inc. C1 [Ireland, David C.; Wang, Conan K. L.; Craik, David J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. [Ireland, David C.; Wang, Conan K. L.; Craik, David J.] Univ Queensland, Australian Res Council, Special Res Ctr Funct & Appl Genom, Brisbane, Qld 4072, Australia. [Ireland, David C.] Univ Queensland, UQ Business Sch, Brisbane, Qld 4072, Australia. [Wilson, Jennifer A.; Gustafson, Kirk R.] NCI, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Craik, DJ (reprint author), Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. EM d.craik@imb.uq.edu.au RI Wang, Conan/D-1481-2010; Craik, David/B-1695-2010 OI Wang, Conan/0000-0002-7973-7632; Craik, David/0000-0003-0007-6796 NR 56 TC 63 Z9 66 U1 0 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2008 VL 90 IS 1 BP 51 EP 60 DI 10.1002/bip.20886 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 254ZS UT WOS:000252627100005 PM 18008336 ER PT J AU Murphy, MAC AF Murphy, M. Angela Corigliano TI The early years: Working at the bench with Bruce (1961-1968) SO BIOPOLYMERS LA English DT Biographical-Item C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Murphy, MAC (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2008 VL 90 IS 3 BP 189 EP 189 DI 10.1002/bip.20935 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 295AZ UT WOS:000255448700007 PM 18428163 ER PT J AU Jin, AJ Nossal, R AF Jin, A. J. Nossal, R. TI Mechanical rigidity of clathrin triskelions, cages and coated vesicles SO BIORHEOLOGY LA English DT Meeting Abstract C1 [Jin, A. J.] NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. [Nossal, R.] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. OI Jin, Albert/0000-0003-3826-1081 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0006-355X J9 BIORHEOLOGY JI Biorheology PY 2008 VL 45 IS 1-2 BP 92 EP 93 PG 2 WC Biophysics; Engineering, Biomedical; Hematology SC Biophysics; Engineering; Hematology GA 344LR UT WOS:000258929100121 ER PT J AU Kho, Y Kim, S Yoon, BS Moon, JH Kim, B Kwak, S Woo, J Oh, S Hong, K Kim, S Kim, H You, S Choi, Y AF Kho, Yoonjung Kim, Sungchan Yoon, Byung Sun Moon, Jai-Hee Kim, Bona Kwak, Suncwook Woo, Junghee Oh, Sejong Hong, Kichang Kim, Saehun Kim, Hyunggee You, Seungkwon Choi, Yunjaie TI Induction of serum amyloid A genes is associated with growth and apoptosis of HC11 mammary epithelial cells SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE serum amyloid A; apoptosis; cytokines; NF kappa B; mammary epithelial cell ID NF-KAPPA-B; ACUTE-PHASE REACTANT; TLH-R ISOFORMS; CASPASE ACTIVATION; GLAND INVOLUTION; MESSENGER-RNA; EXPRESSION; MOUSE; PROTEIN; DEATH AB In this study, we examined the expression and functions of serum amyloid A (SAA) isoforms during apoptosis of HC11 mammary gland epithelial cells. Expression of SAA mRNAs and apoptosis were increased in HC11 cells by serum withdrawal and gradually decreased upon the addition of serum, or epidermal growth factor (EGF). TNF alpha treatment of HC11 cells also induced expression of SAA genes, and the effect on SAA1 and SAA2 expression was suppressed by treatment with MG132, and in cells transfected with a dominant negative mutant form of I kappa B alpha. Similar results were observed in response to interleukin-1 (IL-1), IL-6 and interferon gamma (IFN gamma). Furthermore, overexpression of the SAA1 and SAA2 isoforms suppressed growth and accelerated apoptosis of HC11 cells by increasing caspase 3/7 and caspase 8 activities, but the apoptotic effect of tumor necrosis factor alpha (TNF alpha) on HC11 cells was not enhanced. We found that expression of SAA1 and SAA2, but not SAA3, was regulated by an NF kappa B-dependent pathway, and that overexpression of SAA isoforms accelerated the apoptosis of HC11 cells. C1 [Yoon, Byung Sun; Moon, Jai-Hee; Kim, Bona; Hong, Kichang; Kim, Saehun; Kim, Hyunggee; You, Seungkwon] Korea Univ, Lab Cell Growth & Funct Regulat, Coll Life Sci & Biotechnol, Seoul 136713, South Korea. [Kho, Yoonjung; Kwak, Suncwook; Choi, Yunjaie] Seoul Natl Univ, Coll Agr & Life Sci, Sch Agr & Biotechnol, Seoul 151742, South Korea. [Kim, Sungchan] Hallym Univ, Dept Biochem, Coll Med, Chunchon 200702, Gangwon Do, South Korea. [Woo, Junghee] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. [Oh, Sejong] Chonnam Natl Univ, Div Anim Sci, Coll Agr & Life Sci, Kwangju 500757, South Korea. RP You, S (reprint author), Korea Univ, Lab Cell Growth & Funct Regulat, Coll Life Sci & Biotechnol, Seoul 136713, South Korea. EM bioseung@korea.ac.kr; cyjcow@snu.ac.kr RI Kim, Hyunggee/F-2673-2013; Kang, Phil Jun/F-4716-2013; Choi, Yunjaie /B-4697-2014; You, Seungkwon/H-3067-2015 OI Kim, Hyunggee/0000-0002-4738-0990; NR 51 TC 11 Z9 11 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD JAN PY 2008 VL 72 IS 1 BP 70 EP 81 DI 10.1271/bbb.70374 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA 258BA UT WOS:000252842200010 PM 18175929 ER PT J AU Chen, YH Chatterjee, N Carroll, RJ AF Chen, Yi-Hau Chatterjee, Nilanjan Carroll, Raymond J. TI Retrospective analysis of haplotype-based case-control studies under a flexible model for gene-environment association SO BIOSTATISTICS LA English DT Article DE case control studies; EM algorithm; gene-environment interactions; haplotype; semiparametric methods ID LIKELIHOOD-BASED INFERENCE; ERRORS; PHASE AB Genetic epidemiologic studies often involve investigation of the association of a disease with a genomic region in terms of the underlying haplotypes, that is the combination of alleles at multiple loci along homologous chromosomes. In this article, we consider the problem of estimating haplotype-environment interactions from case-control studies when some of the environmental exposures themselves may be influenced by genetic susceptibility. We specify the distribution of the diplotypes ( haplotype pair) given environmental exposures for the underlying population based on a novel semiparametric model that allows haplotypes to be potentially related with environmental exposures, while allowing the marginal distribution of the diplotypes to maintain certain population genetics constraints such as Hardy-Weinberg equilibrium. The marginal distribution of the environmental exposures is allowed to remain completely nonparametric. We develop a semiparametric estimating equation methodology and related asymptotic theory for estimation of the disease odds ratios associated with the haplotypes, environmental exposures, and their interactions, parameters that characterize haplotype-environment associations and the marginal haplotype frequencies. The problem of phase ambiguity of genotype data is handled using a suitable expectation maximization algorithm. We study the finite-sample performance of the proposed methodology using simulated data. An application of the methodology is illustrated using a case-control study of colorectal adenoma, designed to investigate how the smoking-related risk of colorectal adenoma can be modified by "NAT2," a smoking-metabolism gene that may potentially influence susceptibility to smoking itself. C1 [Chatterjee, Nilanjan] Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20825 USA. [Chen, Yi-Hau] Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Chatterjee, N (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, 6120 Executive Blvd,EPS 8038, Rockville, MD 20825 USA. EM chattern@mail.nih.gov FU NCI NIH HHS [R01 CA057030, R37 CA057030, R37 CA057030-20, U01 CA057030]; NIEHS NIH HHS [P30 ES009106] NR 16 TC 15 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2008 VL 9 IS 1 BP 81 EP 99 DI 10.1093/biostatistics/kxm011 PG 19 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 241TT UT WOS:000251679400006 PM 17490987 ER PT J AU Pfeiffer, RM Carroll, RJ Wheeler, W Whitby, D Mbulaiteye, S AF Pfeiffer, Ruth M. Carroll, Raymond J. Wheeler, William Whitby, Denise Mbulaiteye, Sam TI Combining assays for estimating prevalence of human herpesvirus 8 infection using multivariate mixture models SO BIOSTATISTICS LA English DT Article DE diagnostic tests; mixture models; semi-nonparametric densities; semiparametrics; sensitivity; specificity; transformations ID DENSITY-ESTIMATION; IDENTIFICATION; TRANSFUSION; DIAGNOSIS AB For many diseases, it is difficult or impossible to establish a definitive diagnosis because a perfect "gold standard" may not exist or may be too costly to obtain. In this paper, we propose a method to use continuous test results to estimate prevalence of disease in a given population and to estimate the effects of factors that may influence prevalence. Motivated by a study of human herpesvirus 8 among children with sickle-cell anemia in Uganda, where 2 enzyme immunoassays were used to assess infection status, we fit 2-component multivariate mixture models. We model the component densities using parametric densities that include data transformation as well as flexible transformed models. In addition, we model the mixing proportion, the probability of a latent variable corresponding to the true unknown infection status, via a logistic regression to incorporate covariates. This model includes mixtures of multivariate normal densities as a special case and is able to accommodate unusual shapes and skewness in the data. We assess model performance in simulations and present results from applying various parameterizations of the model to the Ugandan study. C1 [Pfeiffer, Ruth M.] Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Wheeler, William] Informat Management Serv Inc, Rockville, MD 20852 USA. [Whitby, Denise; Mbulaiteye, Sam] NCI, Viral Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. RP Pfeiffer, RM (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, 6120 Executive Blvd,EPS-8030, Bethesda, MD 20892 USA. EM pfeiffer@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU NCI NIH HHS [CO-12400, CA-57030, N01CO12400, R01 CA057030, R37 CA057030, R37 CA057030-20, U01 CA057030]; NIEHS NIH HHS [P30 ES009106, P30-ES09106] NR 15 TC 8 Z9 8 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2008 VL 9 IS 1 BP 137 EP 151 DI 10.1093/biostatistics/kxm018 PG 15 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 241TT UT WOS:000251679400010 PM 17566074 ER PT J AU Nickel, JC Tripp, DA Chuai, S Litwin, MS McNaughton-Collins, M Landis, JR Alexander, RB Schaeffer, AJ O'Leary, MP Pontari, MA White, P Mullins, C Nyberg, L Kusek, J Grp, NCS AF Nickel, J. Curtis Tripp, Dean A. Chuai, Shannon Litwin, Mark S. McNaughton-Collins, Mary Landis, J. Richard Alexander, Richard B. Schaeffer, Anthony J. O'Leary, Michael P. Pontari, Michel A. White, Paige Mullins, Christopher Nyberg, Leroy Kusek, John Grp, N. I. H. C. P. C. R. N. Study TI Psychosocial variables affect the quality of life of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome SO BJU INTERNATIONAL LA English DT Article DE chronic prostatitis; chronic pelvic pain syndrome; quality of life; psychosocial ID VALIDATION; ADJUSTMENT; SYMPTOMS; COHORT; SCALE AB OBJECTIVE To examine interactions between demographic, pain, urinary, psychological and environmental predictors of quality of life (QOL) in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS In all, 253 men previously enrolled in the National Institutes of Health Chronic Prostatitis Cohort study in North American tertiary-care clinical centres (six in the USA and one in Canada) self-reported with validated instruments, including the QOL subscales of the Short Form-12 (physical, SF12-PCS; and mental, SF12-MCS), demographics, urinary symptoms, depression, current pain, pain coping, 'catastrophising' (catastrophic thinking about pain), pain control, social support and solicitous responses from a partner. Data were collected through a one-time survey. Covariates determined to be significant were entered into a multivariable regression model predicting SF12-PCS and SF12-MCS. RESULTS Adjusting for covariates, regression models showed that poorer SF12-PCS scores were predicted by worse urinary function (P < 0.001) and increased use of pain-contingent resting as a coping strategy (P = 0.026). Further, poorer SF12-MCS scores were predicted by greater pain catastrophizing (P = 0.002) and lower perceptions of social support (P < 0.001). In separate follow-up analyses, helplessness was the significant catastrophizing subscale (P < 0.001), while support from family and friends were the significant social support subscales (P = 0.002 and < 0.001). CONCLUSIONS These data suggest that specific coping and environmental factors (i.e. catastrophizing, pain-contingent resting, social support) are significant in understanding how patients with CP/CPPS adjust. These data can be used to develop specific cognitive-behavioural programmes for men with CP/CPPS who are refractory to standard medical therapy. C1 Queens Univ, Dept Urol, Kingston, ON, Canada. Queens Univ, Dept Psychol, Kingston, ON, Canada. Queens Univ, Dept Anaesthesiol & Urol, Kingston, ON, Canada. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Maryland, Sch Med, VA Maryland Hlth Care Syst, Baltimore, MD USA. N Western Univ, Chicago, IL USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Mississippi, University, MS 38677 USA. NIDDK, Bethesda, MD USA. RP Nickel, JC (reprint author), Queens Univ, Dept Urol, Kingston, ON, Canada. RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK NIH HHS [U01 DK53732, U01 DK53734, U01 DK53736, U01 DK53730, U01 DK53738, U01 DK53746, U01 DK53752] NR 20 TC 32 Z9 42 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2008 VL 101 IS 1 BP 59 EP 64 DI 10.1111/j.1464-410X.2007.07196.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 239FA UT WOS:000251503000013 PM 17924985 ER PT J AU Kigozi, G Watya, S Polis, CB Buwembo, D Kiggundu, V Wawer, MJ Serwadda, D Nalugoda, F Kiwanuka, N Bacon, MC Ssempijja, V Makumbi, F Gray, RH AF Kigozi, Godfrey Watya, Stephen Polis, Chelsea B. Buwembo, Denis Kiggundu, Valerian Wawer, Maria J. Serwadda, David Nalugoda, Fred Kiwanuka, Noah Bacon, Melanie C. Ssempijja, Victor Makumbi, Frederick Gray, Ronald H. TI The effect of male circumcision on sexual satisfaction and function, results from a randomized trial of male circumcision for human immunodeficiency virus prevention, Rakai, Uganda SO BJU INTERNATIONAL LA English DT Article DE male circumcision; HIV; randomized trial; sexual satisfaction and function; Uganda ID PENILE SENSITIVITY; ERECTILE FUNCTION; HIV PREVENTION; MEN; INTERVENTION; RISK AB OBJECTIVE To investigate the relationship between adult male circumcision and sexual satisfaction and function in men, as observational studies on the effect of adult male circumcision on sexual satisfaction show conflicting results. SUBJECTS AND METHODS We investigated self-reported sexual satisfaction and function among men enrolled in a randomized trial of male circumcision for human immunodeficiency virus (HIV) prevention conducted in Rakai, Uganda. In all, 4456 sexually experienced HIV-negative males aged 15-49 years were enrolled; 2210 were randomized to receive immediate circumcision (intervention arm) and 2246 to circumcision delayed for 24 months (control arm). Men were followed up at 6, 12 and 24 months, and information on sexual desire, satisfaction and erectile dysfunction was collected. These variables were compared between the study arms and over time within the study arms, using chi-square or Fisher's exact tests. The trial registration number is NCT00425984. RESULTS There were no differences between the study arms at enrolment and problems with sexual satisfaction and function were reported by < 2% of participants in both study arms at all time points. At 6 months, no difficulty with penetration was reported by 98.6% of circumcised men and 99.4% of controls (P = 0.02), and no pain on intercourse was reported by 99.4% circumcised and 98.8% of uncircumcised men (P = 0.05). There were no differences between the study arms in penetration or dyspareunia at later visits. Sexual satisfaction increased from 98.0% at enrolment to 99.9% at 2 years among the controls (P < 0.001), but there was no trend in satisfaction among circumcised men (enrolment 98.5%, 2 years 98.4%, P = 0.8). CONCLUSION Adult male circumcision does not adversely affect sexual satisfaction or clinically significant function in men. C1 Makerere Univ, Mulago Hosp, Inst Publ Hlth, Rakai Hlth Sci Program, Kampala, Uganda. Makerere Univ, Mulago Hosp, Dept Surg, Urol Unit, Kampala, Uganda. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Kigozi, G (reprint author), Makerere Univ, Mulago Hosp, Inst Publ Hlth, Rakai Hlth Sci Program, Kampala, Uganda. OI Polis, Chelsea/0000-0002-1031-7074 NR 18 TC 70 Z9 74 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2008 VL 101 IS 1 BP 65 EP 70 DI 10.1111/j.1464-410X.2007.07369.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 239FA UT WOS:000251503000014 PM 18086100 ER PT J AU Singh, AK Krieger, A Lattouf, JB Guion, P Grubb, RL Albert, PS Metzger, G Ullman, K Smith, S Fichtinger, G Ocak, I Choyke, P Menard, C Coleman, J AF Singh, Anurag K. Krieger, Axel Lattouf, Jean-Baptiste Guion, Peter Grubb, Robert L., III Albert, Paul S. Metzger, Greg Ullman, Karen Smith, Sharon Fichtinger, Gabor Ocak, Iclal Choyke, Peter Menard, Cynthia Coleman, Jonathan TI Patient selection determines the prostate cancer yield of dynamic contrast-enhanced magnetic resonance imaging-guided transrectal biopsies in a closed 3-Tesla scanner SO BJU INTERNATIONAL LA English DT Article DE dynamic contrast enhancement; PSA level; TRUS; image-guided; biopsy ID NEEDLE-BIOPSY; TUMOR FOCI; MRI; MEN; ANTIGEN; SPECTROSCOPY; CARCINOMA; ACCURACY; MRSI; PSA AB OBJECTIVE To evaluate the cancer yield of transrectal prostate biopsies in a 3-T magnetic resonance imaging (MRI) scanner in patients with elevated prostate specific antigen (PSA) levels and recent negative transrectal ultrasonography (TRUS)-guided prostate biopsies. PATIENTS AND METHODS Between July 2004 and November 2005, patients with at least one previous negative prostate biopsy within the previous 12 months had MRI-guided biopsy of the prostate in a 3-T MRI scanner. Patients with previous positive biopsies for cancer were excluded. Target selection was based on T2-weighted imaging and dynamic contrast-enhanced (DCE) imaging studies. RESULTS Thirteen patients were eligible; their median (range) age was 61 (47-74) years and PSA value 4.90 (1.3-12.3) ng/mL. Most patients had one previous negative biopsy (range 1-4). Four patients had a family history of prostate cancer. There were 37 distinct targets based on T2-weighted imaging. Fifteen of 16 distinct DCE abnormalities were co-localized with a target based on T2-weighted imaging. Despite this correlation, only one of 13 patients had a directed biopsy positive for cancer. Including systematic biopsies, two of 13 patients had a biopsy positive for prostate cancer. One patient had prostate intraepithelial neoplasia and one had atypical glands in the specimen. CONCLUSION The prostate-cancer yield of transrectal biopsies in a 3-T MRI scanner, among patients with recent negative TRUS-guided prostate biopsies, is similar to repeat systematic TRUS-guided biopsy. DCE correlates with T2-imaging but does not appear to improve prostate cancer yield in this population. C1 [Singh, Anurag K.; Guion, Peter; Ullman, Karen; Smith, Sharon] NCI, Radiat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Lattouf, Jean-Baptiste; Grubb, Robert L., III; Coleman, Jonathan] NCI, Urol Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biomet Res Branch, Natl Inst Hlth, DCTD, Bethesda, MD 20892 USA. [Ocak, Iclal; Choyke, Peter] NCI, Mol Imaging Program, Natl Inst Hlth, Bethesda, MD 20892 USA. [Krieger, Axel; Fichtinger, Gabor] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. [Metzger, Greg] Univ Minnesota, Ctr Magnet Resonance Hosp, Minneapolis, MN 55455 USA. [Menard, Cynthia] Univ Toronto, Princess Margaret Hosp, Radiat Med Program, Toronto, ON, Canada. RP Singh, AK (reprint author), NCI, Radiat Oncol Branch, Natl Inst Hlth, 10 Ctr Dr, Bethesda, MD 20892 USA. EM Anurag.Singh@RoswellPark.org OI Coleman, Jonathan/0000-0002-6428-7835 FU Intramural NIH HHS; NIBIB NIH HHS [EB002963-01] NR 23 TC 25 Z9 28 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2008 VL 101 IS 2 BP 181 EP 185 DI 10.1111/j.1464-410X.2007.07219.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 242ZF UT WOS:000251764000009 PM 17922874 ER PT J AU Machado, RF AF Machado, Roberto F. TI Amino acids and the erythrocyte under stress? SO BLOOD LA English DT Editorial Material ID SICKLE-CELL-DISEASE; NITRIC-OXIDE; PULMONARY-HYPERTENSION; HEMOGLOBIN; HEMOLYSIS AB In this issue of Blood, Morris and colleagues show that erythrocyte glutathione and glutamine levels are low in patients with sickle cell disease (SCD) and that these markers are linked to markers of hemolysis and pulmonary hypertension. C1 [Machado, Roberto F.] NHLBI, Bethesda, MD 20892 USA. RP Machado, RF (reprint author), NHLBI, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2008 VL 111 IS 1 BP 2 EP 2 DI 10.1182/blood-2007-09-113407 PG 1 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000002 ER PT J AU Uzel, G Tng, E Rosenzweig, SD Hsu, AP Shaw, JM Horwitz, ME Linton, GF Anderson, SM Kirby, MR Oliveira, JB Brown, MR Fleisher, TA Law, SKA Holland, SM AF Uzel, Gulbu Tng, Emilia Rosenzweig, Sergio D. Hsu, Amy P. Shaw, Jacqueline M. Horwitz, Mitchell E. Linton, Gilda F. Anderson, Stacie M. Kirby, Martha R. Oliveira, Jao B. Brown, Margaret R. Fleisher, Thomas A. Law, S. K. Alex Holland, Steven M. TI Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1) SO BLOOD LA English DT Article ID IN-VIVO REVERSION; SEVERE COMBINED IMMUNODEFICIENCY; ADENOSINE-DEAMINASE DEFICIENCY; WISKOTT-ALDRICH-SYNDROME; T-CELLS; INHERITED MUTATION; P150,95 GLYCOPROTEINS; REVERTANT MOSAICISM; SOMATIC MOSAICISM; MISSENSE MUTATION AB Leukocyte adhesion deficiency type-1 (LAD-1) is an autosomal recessive immunodeficiency caused by mutations in the beta 2 integrin, C1318, that impair CD11/CD18 heterodimer surface expression and/or function. Absence of functional CD11/CD18 integrins on leukocytes, particularly neutrophils, leads to their incapacity to adhere to the endothelium and migrate to sites of infection. We studied 3 LAD-1 patients with markedly diminished neutrophil CD18 expression, each of whom had a small population of lymphocytes with normal CD18 expression (CD18(+)). These CD18(+) lymphocytes were predominantly cytotoxic T cells, with a memory/effector phenotype. Microsatellite analyses proved patient origin of these cells. Sequencing of T-cell subsets showed that in each patient one CD18 allele had undergone further mutation. Interestingly, all 3 patients were young adults with inflammatory bowel disease. Somatic reversions of inherited mutations in primary T-cell immunodeficiencies are typically associated with milder clinical phenotypes. We hypothesize that these somatic revertant CD18(+) cytotoxic T lymphocytes (CTLs) may have altered immune regulation. The discovery of 3 cases of reversion mutations in LAD-1 at one center suggests that this may be a relatively common event in this rare disease. C1 [Uzel, Gulbu; Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Tng, Emilia; Shaw, Jacqueline M.; Law, S. K. Alex] Univ Oxford, Dept Biochem, Immunohistochem Unit, MRC, Oxford OX1 3QU, England. [Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Serv Immunol, Buenos Aires, DF, Argentina. [Horwitz, Mitchell E.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Linton, Gilda F.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Anderson, Stacie M.; Kirby, Martha R.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Oliveira, Jao B.; Brown, Margaret R.; Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Serv Immunol, Bethesda, MD 20892 USA. [Law, S. K. Alex] Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore. RP Uzel, G (reprint author), Bldg 10,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM guzel@mail.nih.gov; smh@nih.gov RI Law, Alex/A-2212-2011; OI Oliveira, Joao/0000-0001-9388-8173 FU Intramural NIH HHS NR 40 TC 33 Z9 34 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2008 VL 111 IS 1 BP 209 EP 218 DI 10.1182/blood-2007-04-082552 PG 10 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000032 PM 17875809 ER PT J AU Rezvani, K Yong, ASM Mielke, S Savani, BN Musse, L Superata, J Jafarpour, B Boss, C Barrett, AJ AF Rezvani, Katayoun Yong, Agnes S. M. Mielke, Stephan Savani, Bipin N. Musse, Laura Superata, Jeanine Jafarpour, Behnam Boss, Carol Barrett, A. John TI Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies SO BLOOD LA English DT Article ID TUMOR GENE WT1; CHRONIC MYELOGENOUS LEUKEMIA; RESIDUAL DISEASE DETECTION; POLYMERASE-CHAIN-REACTION; CANCER PROGRAM; LYMPHOCYTES; TRANSPLANTATION; PROTEINASE-3; EXPRESSION; TRANSCRIPTS AB We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1. Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor. Patients were reviewed weekly for 4 weeks to monitor toxicity and immunologic responses. Toxicity was limited to grades 1 to 2. Using peptide/HLA-A*0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination. To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination. Responses occurred as early as 1 week after vaccination. After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect. Conversely, loss of response was associated with reappearance of WT1 transcripts (P <.01). This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic. These results support further studies of combination immunization strategies in leukemia patients. This study is registered at http:// clinicaltrials.gov as NCT00313638. C1 [Rezvani, Katayoun; Yong, Agnes S. M.; Mielke, Stephan; Savani, Bipin N.; Musse, Laura; Superata, Jeanine; Jafarpour, Behnam; Boss, Carol; Barrett, A. John] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rezvani, K (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg,Hatfield CRC,Rm 3-5410,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM rezvanik@nhlbi.nih.gov NR 31 TC 215 Z9 227 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2008 VL 111 IS 1 BP 236 EP 242 DI 10.1182/blood-2007-08-108241 PG 7 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000035 PM 17875804 ER PT J AU Du, X Nagata, S Ise, T Stetler-Stevenson, M Pastan, I AF Du, Xing Nagata, Satoshi Ise, Tomoko Stetler-Stevenson, Maryalice Pastan, Ira TI FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia, and B-cell non-Hodgkin lymphoma as a target of immunotoxins SO BLOOD LA English DT Article ID RECEPTOR-LIKE MOLECULES; PHASE-I TRIAL; MONOCLONAL-ANTIBODIES; MULTIPLE-MYELOMA; MALIGNANCIES; EXPRESSION; PROTEIN; TISSUE; IDENTIFICATION; ANTIGEN AB FCRL1 (Fc receptor-like 1) is a cell-surface membrane protein belonging to FCRL family and is preferentially expressed on B cells. To evaluate FcRL1 as an immunotherapy target for B-cell malignancies, we prepared anti-FCRL1 mAbs without cross-reactivity to other FCRL family proteins and analyzed FCRL1 protein expression on malignant cells from patients and on B-cell lines. Frequent FCRL1 expression was observed by flow cytometry on 12 B-cell non-Hodgkin lymphoma (B-NHL) cell lines and many patient samples: 12 of 14 chronic lymphocytic leukemia (CLL), 7 of 7 follicular lymphoma (FL), 13 of 17 hairy cell leukemia (HCL), and 2 of 3 mantle cell lymphoma (MCL). Two recombinant immunotoxins, E3(Fv)-PE38 and E9(Fv)-PE38, were constructed. Both immunotoxins bound to FCRL1-positive cells with similar affinities (3.4 and 3.2 nM) and were cytotoxic to cell lines, but E9(Fv)-PE38 was 4- to 20-fold more cytotoxic than E3(Fv)-PE38. The concentrations that inhibited response by 50% (IC(50)s) of E9(Fv)-PE38 on 11 different FCRL1-positive cell lines ranged from 1.0 ng/mL to 90 ng/mL and correlated with the FCRL1 expression levels. Our results suggest that anti-FCRL1 immunotoxin E9(Fv)-PE38 exhibits remarkably specific cytotoxicity and merits further evaluation for the treatment of FCRL1-positive malignancies, including CLL, HCL, FL, MCL, and other B-NHL. C1 [Du, Xing; Nagata, Satoshi; Ise, Tomoko; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Rm 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov RI Du, Xing/B-1113-2011 FU Intramural NIH HHS NR 33 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2008 VL 111 IS 1 BP 338 EP 343 DI 10.1182/blood-2007-07-102350 PG 6 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000047 PM 17895404 ER PT J AU Bessette, K Lang, ML Fava, RA Grundy, M Heinen, J Horne, L Spolski, R Al-Shami, A Morse, HC Leonard, WJ Kelly, JA AF Bessette, Katherine Lang, Mark L. Fava, Roy A. Grundy, Martin Heinen, Jennifer Horne, Laurie Spolski, Rosanne Al-Shami, Amin Morse, Herbert C., III Leonard, Warren J. Kelly, John A. TI Stat5b transgene is capable of inducing CD8(+) lymphoblastic lymphoma in the absence of normal TCR/MHC signaling SO BLOOD LA English DT Article ID T-CELL DEVELOPMENT; FUNCTIONALLY DISTINCT SUBSETS; LINEAGE COMMITMENT; GENE-EXPRESSION; THYMOCYTE DEVELOPMENT; RECEPTOR-ALPHA; FLOW-CYTOMETRY; DEFICIENT MICE; GAMMA-DELTA; NKT-CELLS AB Stat5 proteins are critical signaling molecules activated by many cytokines. Within the immune system, Stat5 plays important roles related to the development of thymocytes and proliferation of T cells. Stat5 has been implicated in malignant transformation, and moreover, the activated tyrosine phosphorylated form of Stat5 is frequently observed in human lymphomas. We previously demonstrated the oncogenic potential of Stat5, with thymic lymphoblastic lymphomas developing in a significant proportion of trans-genic (TG) mice overexpressing Stat5a or Stat5b in lymphocytes. In addition, immunization or expression of a T-cell receptor (TCR) transgene augmented the rate of tumor formation. Here, we investigate the mechanism of Stat5-mediated lymphomagenesis by exploring the contributions of major histocompatibility complex (MHC)/TCR and pre-TCR signals. We present data demonstrating that Stat5b TG mice unexpectedly develop CD8(+) lymphoma even in the absence of eithertion. Indeed, acceleration of Stat5b transgene-mediated lymphoma occurred on TCR alpha(-/-) and pre-TCR alpha(-/-) backgrounds. In light of these data, we propose a model in which alterations in T-cell development at the double-negative/double-positive (DN/DP) stages cooperate with cytokine-mediated pathways in immature thymocytes to give rise to lymphoblastic T-cell lymphomas in Stat5b TG mice. C1 [Bessette, Katherine; Fava, Roy A.; Grundy, Martin; Heinen, Jennifer; Kelly, John A.] White River Junct Vet Assoc, White River Jct, VT USA. [Bessette, Katherine] Dartmouth Med Sch, Dept Microimmunol, Lebanon, NH USA. [Spolski, Rosanne; Al-Shami, Amin; Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. [Morse, Herbert C., III] NIAID, Immunopathol Lab, Rockville, MD USA. RP Kelly, JA (reprint author), 2-123 Bldg 44,215 N Main St, White River Jct, VT 05009 USA. EM john.a.kelly@dartmouth.edu RI Al-Shami, Amin/D-3889-2009 FU Intramural NIH HHS; NCRR NIH HHS [P20 RR016437, 2P20RR016437-06] NR 70 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2008 VL 111 IS 1 BP 344 EP 350 DI 10.1182/blood-2007-04-084707 PG 7 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000048 PM 17890450 ER PT J AU Shevach, EM AF Shevach, Ethan M. TI Response: Anti-human FOXP3 mAb PCH101 stains activated human nalive T cells nonspecifically SO BLOOD LA English DT Letter C1 [Shevach, Ethan M.] NIH, NIAID, Immunol Lab, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIH, NIAID, Immunol Lab, 10 Ctr Dr,Bldg 10,Rm 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2008 VL 111 IS 1 BP 464 EP 466 PG 3 WC Hematology SC Hematology GA 246IZ UT WOS:000252002000065 ER PT J AU Buonaguro, L Monaco, A Arico, E Wang, E Tornesello, ML Lewis, GK Marincola, FM Buonaguro, FM AF Buonaguro, Luigi Monaco, Alessandro Arico, Eleonora Wang, Ena Tornesello, Maria Lina Lewis, George K. Marincola, Franco M. Buonaguro, Franco M. TI Gene expression profile of peripheral blood mononuclear cells in response to HIV-VLPs stimulation SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Italian-Society-of-Bioinformatics CY APR 26-28, 2007 CL Naples, ITALY SP Italian Soc Bioinformat ID VIRUS-LIKE PARTICLES; HUMAN DENDRITIC CELLS; CROSS-PRESENTATION; NEUTRALIZING ANTIBODIES; T-LYMPHOCYTES; CLADE-A; MATURATION; ACTIVATION; INDUCTION; CHEMOKINE AB Background: Baculovirus-expressed HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs) induce maturation and activation of monocyte-derived dendritic cells (MDDCs) with a production of Th1-and Th2-specific cytokines. Results: The analysis of genomic transcriptional profile of MDDCs, obtained from normal healthy donors and activated by HIV-VLPs, show the modulation of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. Similar data are obtained using peripheral blood mononuclear cells (PBMCs), without further selection, showing the feasibility of a direct and "simplified" experimental procedure. Conclusions: The results here described show that the maturation pattern induced by HIV-VLPs in ex vivo generated MDDCs, can be observed also in CD14-expressing freshly derived PBMCs, with the possible identification of genetic predictors of individual response to immunogens. C1 [Buonaguro, Luigi; Tornesello, Maria Lina; Buonaguro, Franco M.] Ist Nazl Tumori Fond D Pascale, Lab Viral Oncogenesis & Immunotherapies, I-80131 Naples, Italy. [Buonaguro, Luigi; Tornesello, Maria Lina; Buonaguro, Franco M.] Ist Nazl Tumori Fond D Pascale, Dept Expt Oncol, AIDS Reference Ctr, I-80131 Naples, Italy. [Monaco, Alessandro; Wang, Ena; Marincola, Franco M.] NIH, Dept Transfus Med, Immunogenet Sect, Bethesda, MD 20892 USA. [Lewis, George K.] Univ Maryland, Inst Human Virol, Sch Med, Baltimore, MD 21201 USA. [Arico, Eleonora] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. RP Buonaguro, FM (reprint author), Ist Nazl Tumori Fond D Pascale, Lab Viral Oncogenesis & Immunotherapies, I-80131 Naples, Italy. EM irccsvir@unina.it; monacoal@cc.nih.gov; aricoe@cc.nih.gov; EWang@mail.cc.nih.gov; irccsvir@unina.it; glewis@ihv.umaryland.edu; FMarincola@mail.cc.nih.gov; irccsvir@unina.it RI Tornesello, Maria Lina/A-1564-2009; Monaco, Alessandro/O-5338-2015; OI Tornesello, Maria Lina/0000-0002-3523-3264; Monaco, Alessandro/0000-0002-9941-7003; Buonaguro, Luigi/0000-0002-6380-7114 NR 39 TC 24 Z9 24 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 2 AR S5 DI 10.1186/1471-2105-9-S2-S5 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345UP UT WOS:000259022900005 PM 18387207 ER PT J AU Demner-Fushman, D Ananiadou, S Cohen, KB Pestian, J Tsujii, J Webber, B AF Demner-Fushman, Dina Ananiadou, Sophia Cohen, K. Bretonnel Pestian, John Tsujii, Jun'ichi Webber, Bonnie TI Themes in biomedical natural language processing: BioNLP08 SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT Natural Language Processing in Biomedicine (BioNLP), ACL Workshop CY JUN 19, 2008 CL Columbus, OH SP ACL C1 [Demner-Fushman, Dina] US Natl Lib Med, Bethesda, MD 20894 USA. [Ananiadou, Sophia; Tsujii, Jun'ichi] Univ Manchester, Manchester M7 1DN, Lancs, England. [Cohen, K. Bretonnel] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. [Pestian, John] Cincinnati Childrens Hosp & Med Ctr, Computat Med Ctr, Cincinnati, OH 45229 USA. [Tsujii, Jun'ichi] Univ Tokyo, Tokyo 1138654, Japan. [Webber, Bonnie] Univ Edinburgh, Edinburgh EH8 9LW, Midlothian, Scotland. RP Demner-Fushman, D (reprint author), US Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM ddemner@mail.nih.gov; sophia.ananiadou@manchester.ac.uk; Kevin.Cohen@gmail.com; john.pestian@cchmc.org; tsujii@is.s.u-tokyo.ac.jp; bonnie@inf.ed.ac.uk FU Biotechnology and Biological Sciences Research Council [BB/E004431/1] NR 11 TC 1 Z9 1 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 11 AR S1 DI 10.1186/1471-2105-9-S11-S1 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 381JR UT WOS:000261532700001 PM 19025685 ER PT J AU Li, GZ Meng, HH Lu, WC Yang, JY Yang, MQ AF Li, Guo-Zheng Meng, Hao-Hua Lu, Wen-Cong Yang, Jack Y. Yang, Mary Qu TI Asymmetric bagging and feature selection for activities prediction of drug molecules SO BMC BIOINFORMATICS LA English DT Article CT Symposium of Computations in Bioinformatics and Bioscience (SCBB07) CY AUG 13-15, 2007 CL Iowa City, IA ID SUPPORT VECTOR MACHINES; QSAR; CLASSIFICATION; DISCOVERY; MODELS; DESCRIPTORS; ENSEMBLES; RELEVANCE; AGENTS; PLS AB Background: Activities of drug molecules can be predicted by QSAR ( quantitative structure activity relationship) models, which overcomes the disadvantages of high cost and long cycle by employing the traditional experimental method. With the fact that the number of drug molecules with positive activity is rather fewer than that of negatives, it is important to predict molecular activities considering such an unbalanced situation. Results: Here, asymmetric bagging and feature selection are introduced into the problem and asymmetric bagging of support vector machines (asBagging) is proposed on predicting drug activities to treat the unbalanced problem. At the same time, the features extracted from the structures of drug molecules affect prediction accuracy of QSAR models. Therefore, a novel algorithm named PRIFEAB is proposed, which applies an embedded feature selection method to remove redundant and irrelevant features for asBagging. Numerical experimental results on a data set of molecular activities show that asBagging improve the AUC and sensitivity values of molecular activities and PRIFEAB with feature selection further helps to improve the prediction ability. Conclusion: Asymmetric bagging can help to improve prediction accuracy of activities of drug molecules, which can be furthermore improved by performing feature selection to select relevant features from the drug molecules data sets. C1 [Yang, Mary Qu] US Dept HHS, NHGRI, NIH, Bethesda, MD 20852 USA. [Li, Guo-Zheng] Shanghai Univ, Inst Syst Biol, Shanghai 200444, Peoples R China. [Li, Guo-Zheng; Meng, Hao-Hua] Shanghai Univ, Sch Comp Engn & Sci, Shanghai 200072, Peoples R China. [Lu, Wen-Cong] Shanghai Univ, Sch Sci, Dept Chem, Shanghai 200444, Peoples R China. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02140 USA. RP Yang, MQ (reprint author), US Dept HHS, NHGRI, NIH, Bethesda, MD 20852 USA. EM gzli@shu.edu.cn; mhhtj@shu.edu.cn; wclu@staff.shu.edu.cn; jyang@bwh.harvard.edu; yangma@mail.NIH.GOV RI Li, Guo-Zheng /D-5744-2011 OI Li, Guo-Zheng /0000-0001-5568-0347 NR 42 TC 17 Z9 20 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 AR S7 DI 10.1186/1471-2105-9-S6-S7 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345UW UT WOS:000259023700007 PM 18541060 ER PT J AU Neveol, A Shooshan, SE Claveau, V AF Neveol, Aurelie Shooshan, Sonya E. Claveau, Vincent TI Automatic inference of indexing rules for MEDLINE SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT Natural Language Processing in Biomedicine (BioNLP), ACL Workshop CY JUN 19, 2008 CL Columbus, OH SP ACL AB Background: Indexing is a crucial step in any information retrieval system. In MEDLINE, a widely used database of the biomedical literature, the indexing process involves the selection of Medical Subject Headings in order to describe the subject matter of articles. The need for automatic tools to assist MEDLINE indexers in this task is growing with the increasing number of publications being added to MEDLINE. Methods: In this paper, we describe the use and the customization of Inductive Logic Programming (ILP) to infer indexing rules that may be used to produce automatic indexing recommendations for MEDLINE indexers. Results: Our results show that this original ILP-based approach outperforms manual rules when they exist. In addition, the use of ILP rules also improves the overall performance of the Medical Text Indexer (MTI), a system producing automatic indexing recommendations for MEDLINE. Conclusion: We expect the sets of ILP rules obtained in this experiment to be integrated into MTI. C1 [Neveol, Aurelie; Shooshan, Sonya E.] Natl Lib Med, Bethesda, MD 20894 USA. [Claveau, Vincent] CNRS, IRISA, F-35042 Rennes, France. RP Neveol, A (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM neveola@nlm.nih.gov; sonya@nlm.nih.gov; vincent.claveau@irisa.fr FU Intramural NIH HHS NR 21 TC 6 Z9 6 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 11 AR S11 DI 10.1186/1471-2105-9-S11-S11 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 381JR UT WOS:000261532700011 PM 19025687 ER PT J AU Shi, LM Jones, WD Jensen, RV Harris, SC Perkins, RG Goodsaid, FM Guo, L Croner, LJ Boysen, C Fang, H Qian, F Amur, S Bao, WJ Barbacioru, CC Bertholet, V Cao, XM Chu, TM Collins, PJ Fan, XH Frueh, FW Fuscoe, JC Guo, X Han, J Herman, D Hong, HX Kawasaki, ES Li, QZ Luo, YL Ma, YQ Mei, N Peterson, RL Puri, RK Shippy, R Su, ZQ Sun, YA Sun, HM Thorn, B Turpaz, Y Wang, C Wang, SJ Warrington, JA Willey, JC Wu, J Xie, Q Zhang, L Zhang, L Zhong, S Wolfinger, RD Tong, WD AF Shi, Leming Jones, Wendell D. Jensen, Roderick V. Harris, Stephen C. Perkins, Roger G. Goodsaid, Federico M. Guo, Lei Croner, Lisa J. Boysen, Cecilie Fang, Hong Qian, Feng Amur, Shashi Bao, Wenjun Barbacioru, Catalin C. Bertholet, Vincent Cao, Xiaoxi Megan Chu, Tzu-Ming Collins, Patrick J. Fan, Xiaohui Frueh, Felix W. Fuscoe, James C. Guo, Xu Han, Jing Herman, Damir Hong, Huixiao Kawasaki, Ernest S. Li, Quan-Zhen Luo, Yuling Ma, Yunqing Mei, Nan Peterson, Ron L. Puri, Raj K. Shippy, Richard Su, Zhenqiang Sun, Yongming Andrew Sun, Hongmei Thorn, Brett Turpaz, Yaron Wang, Charles Wang, Sue Jane Warrington, Janet A. Willey, James C. Wu, Jie Xie, Qian Zhang, Liang Zhang, Lu Zhong, Sheng Wolfinger, Russell D. Tong, Weida TI The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 5th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY FEB 23-24, 2008 CL Oklahoma City, OK SP MidSouth Computat Biol & Bioinformat Soc ID QUALITY-CONTROL; OLIGONUCLEOTIDE MICROARRAYS; PLATFORM CONSISTENCY; ALTERED EXPRESSION; DNA MICROARRAY; CANCER; ARRAYS; DISCOVERY; NOISE; HYBRIDIZATION AB Background: Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists. Results: Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan - the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent P-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on P-value ranking is an expected mathematical consequence of the high variability of the t-values; the more stringent the P-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations. Conclusion: We recommend the use of FC-ranking plus a non-stringent P cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the P-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and P-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the P criterion balances sensitivity and specificity. C1 [Shi, Leming; Harris, Stephen C.; Guo, Lei; Fan, Xiaohui; Fuscoe, James C.; Mei, Nan; Su, Zhenqiang; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jones, Wendell D.] Express Anal Inc, Durham, NC 27713 USA. [Jensen, Roderick V.] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. [Perkins, Roger G.; Fang, Hong; Qian, Feng; Cao, Xiaoxi Megan; Hong, Huixiao; Sun, Hongmei; Thorn, Brett; Wu, Jie; Xie, Qian] US FDA, Z Tech Corp, NCTR, Jefferson, AR 72079 USA. [Goodsaid, Federico M.; Amur, Shashi; Frueh, Felix W.; Wang, Sue Jane] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Croner, Lisa J.] Biogen Idec Inc, San Diego, CA 92122 USA. [Boysen, Cecilie] ViaLogy Inc, Altadena, CA 91001 USA. [Bao, Wenjun; Chu, Tzu-Ming; Wolfinger, Russell D.] SAS Inst Inc, Cary, NC 27513 USA. [Barbacioru, Catalin C.; Sun, Yongming Andrew] Applied Biosyst, Foster City, CA 94404 USA. [Bertholet, Vincent] Eppendorf Array Technol, B-5000 Namur, Belgium. [Collins, Patrick J.] Agilent Technol, Santa Clara, CA 95051 USA. [Fan, Xiaohui; Turpaz, Yaron] Zhejiang Univ, Pharmaceut Informat Inst, Hangzhou 310027, Peoples R China. [Guo, Xu; Warrington, Janet A.] Affymetrix Inc, Santa Clara, CA 95051 USA. [Han, Jing; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Herman, Damir] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Kawasaki, Ernest S.] Natl Canc Inst, Adv Technol Ctr, Gaithersburg, MD 20877 USA. [Li, Quan-Zhen] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Luo, Yuling; Ma, Yunqing] Panomics Inc, Fremont, CA 94555 USA. [Peterson, Ron L.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Shippy, Richard] GE Healthcare, Tempe, AZ 85284 USA. [Wang, Charles] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Willey, James C.] Ohio Med Univ, Toledo, OH 43614 USA. [Zhang, Liang] CapitalBio Corp, Beijing 102206, Peoples R China. [Zhang, Lu] Solexa Inc, Hayward, CA 94545 USA. [Zhong, Sheng] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov; wjones@expressionanalysis.com; rvjensen@vt.edu; stephen.harris@fda.hhs.gov; roger.perkins@fda.hhs.gov; federico.goodsaid@fda.hhs.gov; lei.guo@fda.hhs.gov; lisa.croner@biogenidec.com; cecilie.boysen@vialogy.com; hong.fang@fda.hhs.gov; feng.qian@fda.hhs.gov; shashi.amur@fda.hhs.gov; wenjun.bao@sas.com; catalin.barbacioru@appliedbiosystems.com; bertholet.v@eppendorf.be; xiaoxicao@gmail.com; tzu-ming.chu@sas.com; jim_collins@affymetrix.com; xiao-hui.fan@fda.hhs.gov; felix@genpad.com; james.fuscoe@fda.hhs.gov; xu_guo@affymetrix.com; jing.han@fda.hhs.gov; damir.herman@gmail.com; huixiao.hong@fda.hhs.gov; kawasaki4244@yahoo.com; quan.li@utsouthwestern.edu; yluo@panomics.com; yma@panomics.com; nan.mei@fda.hhs.gov; ron.peterson@novartis.com; raj.puri@fda.hhs.gov; richard_shippy@affymetrix.com; zhenqiang.su@fda.hhs.gov; sunya@appliedbiosystems.com; hong_mei_sun@yahoo.com; brett.thorn@fda.hhs.gov; turpazmaqc@hotmail.com; charles.wang@cshs.org; suejane.wang@fda.hhs.gov; janet.warrington@jestech.net; jwilley@meduohio.edu; jiewu3@gmail.com; qianxie133@gmail.com; lzhang@capitalbio.com; lzhang@illumina.com; szhong@uiuc.edu; russ.wolfinger@sas.com; weida.tong@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011; Su, Zhenqiang/H-3914-2012; OI mei, nan/0000-0002-3501-9014; Croner, Lisa/0000-0002-3921-1484 NR 56 TC 125 Z9 127 U1 0 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 9 AR S10 DI 10.1186/1471-2105-9-S9-S10 PG 19 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345VE UT WOS:000259024600010 PM 18793455 ER PT J AU Yang, MQ Taylor, J Elnitski, L AF Yang, Mary Qu Taylor, James Elnitski, Laura TI Comparative analyses of bidirectional promoters in vertebrates SO BMC BIOINFORMATICS LA English DT Article CT Symposium of Computations in Bioinformatics and Bioscience (SCBB07) CY AUG 13-15, 2007 CL Iowa City, IA ID GENE ORGANIZATION; HUMAN GENOME AB Background: Orthologous genes with deep phylogenetic histories are likely to retain similar regulatory features. In this report we utilize orthology assignments for pairs of genes co-regulated by bidirectional promoters to map the ancestral history of the promoter regions. Results: Our mapping of bidirectional promoters from humans to fish shows that many such promoters emerged after the divergence of chickens and fish. Furthermore, annotations of promoters in deep phylogenies enable detection of missing data or assembly problems present in higher vertebrates. The functional importance of bidirectional promoters is indicated by selective pressure to maintain the arrangement of genes regulated by the promoter over long evolutionary time spans. Characteristics unique to bidirectional promoters are further elucidated using a technique for unsupervised classification, known as ESPERR. Conclusion: Results of these analyses will aid in our understanding of the evolution of bidirectional promoters, including whether the regulation of two genes evolved as a consequence of their proximity or if function dictated their co-regulation. C1 [Yang, Mary Qu; Elnitski, Laura] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Taylor, James] NYU, Courant Inst Math Sci, New York, NY 10003 USA. RP Elnitski, L (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM yangma@mail.nih.gov; james@cims.nyu.edu; elnitski@mail.nih.gov RI Taylor, James/F-1026-2011 OI Taylor, James/0000-0001-5079-840X FU Intramural NIH HHS NR 9 TC 19 Z9 22 U1 2 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 AR S9 DI 10.1186/1471-2105-9-S6-S9 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345UW UT WOS:000259023700009 PM 18541062 ER PT J AU Zeng, XQ Li, GZ Yang, JY Yang, MQ Wu, GF AF Zeng, Xue-Qiang Li, Guo-Zheng Yang, Jack Y. Yang, Mary Qu Wu, Geng-Feng TI Dimension reduction with redundant gene elimination for tumor classification SO BMC BIOINFORMATICS LA English DT Article CT Symposium of Computations in Bioinformatics and Bioscience (SCBB07) CY AUG 13-15, 2007 CL Iowa City, IA ID PARTIAL LEAST-SQUARES; FEATURE-SELECTION; CANCER CLASSIFICATION; EXPRESSION DATA; PREDICTION AB Background: Analysis of gene expression data for tumor classification is an important application of bioinformatics methods. But it is hard to analyse gene expression data from DNA microarray experiments by commonly used classifiers, because there are only a few observations but with thousands of measured genes in the data set. Dimension reduction is often used to handle such a high dimensional problem, but it is obscured by the existence of amounts of redundant features in the microarray data set. Results: Dimension reduction is performed by combing feature extraction with redundant gene elimination for tumor classification. A novel metric of redundancy based on DIScriminative Contribution (DISC) is proposed which estimates the feature similarity by explicitly building a linear classifier on each gene. Compared with the standard linear correlation metric, DISC takes the label information into account and directly estimates the redundancy of the discriminative ability of two given features. Based on the DISC metric, a novel algorithm named REDISC (Redundancy Elimination based on Discriminative Contribution) is proposed, which eliminates redundant genes before feature extraction and promotes performance of dimension reduction. Experimental results on two microarray data sets show that the REDISC algorithm is effective and reliable to improve generalization performance of dimension reduction and hence the used classifier. Conclusion: Dimension reduction by performing redundant gene elimination before feature extraction is better than that with only feature extraction for tumor classification, and redundant gene elimination in a supervised way is superior to the commonly used unsupervised method like linear correlation coefficients. C1 [Zeng, Xue-Qiang; Li, Guo-Zheng; Wu, Geng-Feng] Shanghai Univ, Sch Comp Engn & Sci, Shanghai 200072, Peoples R China. [Li, Guo-Zheng] Nanjing Univ, State Key Lab Novel Software Technol, Nanjing 210093, Peoples R China. [Yang, Jack Y.] Harvard Univ, Harvard Med Sch, Cambridge, MA 02140 USA. [Yang, Mary Qu] US Dept HHS, NHGRI, NIH, Bethesda, MD 20852 USA. RP Li, GZ (reprint author), Shanghai Univ, Sch Comp Engn & Sci, Shanghai 200072, Peoples R China. EM stamina_zeng@shu.edu.cn; gzli@shu.edu.cn; yang@hadron.mgh.harvard.edu; yangma@mail.NIH.GOV; gfwu@shu.edu.cn RI Li, Guo-Zheng /D-5744-2011 OI Li, Guo-Zheng /0000-0001-5568-0347 NR 23 TC 11 Z9 12 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 AR S8 DI 10.1186/1471-2105-9-S6-S8 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345UW UT WOS:000259023700008 PM 18541061 ER PT J AU Habib, T Zhang, CY Yang, JY Yang, MQ Deng, YP AF Habib, Tanwir Zhang, Chaoyang Yang, Jack Y. Yang, Mary Qu Deng, Youping TI Supervised learning method for the prediction of subcellular localization of proteins using amino acid and amino acid pair composition SO BMC GENOMICS LA English DT Article AB Background: Occurrence of protein in the cell is an important step in understanding its function. It is highly desirable to predict a protein's subcellular locations automatically from its sequence. Most studied methods for prediction of subcellular localization of proteins are signal peptides, the location by sequence homology, and the correlation between the total amino acid compositions of proteins. Taking amino-acid composition and amino acid pair composition into consideration helps improving the prediction accuracy. Results: We constructed a dataset of protein sequences from SWISS-PROT database and segmented them into 12 classes based on their subcellular locations. SVM modules were trained to predict the subcellular location based on amino acid composition and amino acid pair composition. Results were calculated after 10-fold cross validation. Radial Basis Function (RBF) outperformed polynomial and linear kernel functions. Total prediction accuracy reached to 71.8% for amino acid composition and 77.0% for amino acid pair composition. In order to observe the impact of number of subcellular locations we constructed two more datasets of nine and five subcellular locations. Total accuracy was further improved to 79.9% and 85.66%. Conclusions: A new SVM based approach is presented based on amino acid and amino acid pair composition. Result shows that data simulation and taking more protein features into consideration improves the accuracy to a great extent. It was also noticed that the data set needs to be crafted to take account of the distribution of data in all the classes. C1 [Habib, Tanwir; Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Zhang, Chaoyang] Univ So Mississippi, Sch Comp, Hattiesburg, MS 39406 USA. [Yang, Jack Y.] Harvard Univ, Sch Med, Cambridge, MA 02140 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20852 USA. RP Deng, YP (reprint author), Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. EM tanwir.habib@usm.edu; chaoyang.zhang@usm.edu; jyang@bwh.harvard.edu; yangma@mail.nih.gov; youping.deng@usm.edu FU NCRR NIH HHS [2P0RR016476-04] NR 22 TC 12 Z9 14 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR S16 DI 10.1186/1471-2164-9-S1-S16 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100017 PM 18366605 ER PT J AU Li, GZ Bu, HL Yang, MQ Zeng, XQ Yang, JY AF Li, Guo-Zheng Bu, Hua-Long Yang, Mary Qu Zeng, Xue-Qiang Yang, Jack Y. TI Selecting subsets of newly extracted features from PCA and PLS in microarray data analysis SO BMC GENOMICS LA English DT Article ID PARTIAL LEAST-SQUARES; SUPPORT VECTOR MACHINES; GENE-EXPRESSION DATA; TUMOR CLASSIFICATION; DIMENSION REDUCTION; CANCER CLASSIFICATION; PREDICTION; REGRESSION AB Background: Dimension reduction is a critical issue in the analysis of microarray data, because the high dimensionality of gene expression microarray data set hurts generalization performance of classifiers. It consists of two types of methods, i.e. feature selection and feature extraction. Principle component analysis (PCA) and partial least squares (PLS) are two frequently used feature extraction methods, and in the previous works, the top several components of PCA or PLS are selected for modeling according to the descending order of eigenvalues. While in this paper, we prove that not all the top features are useful, but features should be selected from all the components by feature selection methods. Background: Dimension reduction is a critical issue in the analysis of microarray data, because the high dimensionality of gene expression microarray data set hurts generalization performance of classifiers. It consists of two types of methods, i.e. feature selection and feature extraction. Principle component analysis (PCA) and partial least squares (PLS) are two frequently used feature extraction methods, and in the previous works, the top several components of PCA or PLS are selected for modeling according to the descending order of eigenvalues. While in this paper, we prove that not all the top features are useful, but features should be selected from all the components by feature selection methods. Conclusion: Not only the top features newly extracted by PCA or PLS are important, therefore, feature selection should be performed to select subsets from new features to improve generalization performance of classifiers. C1 [Yang, Jack Y.] Harvard Univ, Sch Med, Cambridge, MA 02140 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept HHS, Bethesda, MD 20852 USA. [Li, Guo-Zheng; Bu, Hua-Long; Zeng, Xue-Qiang] Shanghai Univ, Sch Comp Sci & Engn, Shanghai 200072, Peoples R China. [Li, Guo-Zheng] Tongji Univ, Dept Control Sci & Engn, Shanghai 201804, Peoples R China. RP Yang, JY (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02140 USA. EM drgzli@gmail.com; fellowbhl@shu.edu.cn; yangma@mail.NIH.GOV; stamina_zeng@shu.edu.cn; yang@hadron.mgh.harvard.edu RI Li, Guo-Zheng /D-5744-2011 OI Li, Guo-Zheng /0000-0001-5568-0347 NR 34 TC 12 Z9 15 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 2 AR S24 DI 10.1186/1471-2164-9-S2-S24 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JQ UT WOS:000206244200025 PM 18831790 ER PT J AU Liu, QZ Yang, J Chen, ZX Yang, MQ Sung, AH Huang, XD AF Liu, Qingzhong Yang, Jack Chen, Zhongxue Yang, Mary Qu Sung, Andrew H. Huang, Xudong TI Supervised learning-based tagSNP selection for genome-wide disease classifications SO BMC GENOMICS LA English DT Article AB Background: Comprehensive evaluation of common genetic variations through association of single nucleotide polymorphisms (SNPs) with complex human diseases on the genome-wide scale is an active area in human genome research. One of the fundamental questions in a SNP-disease association study is to find an optimal subset of SNPs with predicting power for disease status. To find that subset while reducing study burden in terms of time and costs, one can potentially reconcile information redundancy from associations between SNP markers. Results: We have developed a feature selection method named Supervised Recursive Feature Addition (SRFA). This method combines supervised learning and statistical measures for the chosen candidate features/SNPs to reconcile the redundancy information and, in doing so, improve the classification performance in association studies. Additionally, we have proposed a Support Vector based Recursive Feature Addition (SVRFA) scheme in SNP-disease association analysis. Conclusions: We have proposed using SRFA with different statistical learning classifiers and SVRFA for both SNP selection and disease classification and then applying them to two complex disease data sets. In general, our approaches outperform the well-known feature selection method of Support Vector Machine Recursive Feature Elimination and logic regression-based SNP selection for disease classification in genetic association studies. Our study further indicates that both genetic and environmental variables should be taken into account when doing disease predictions and classifications for the most complex human diseases that have gene-environment interactions. C1 [Liu, Qingzhong; Sung, Andrew H.] New Mexico Inst Min & Technol, Dept Comp Sci, Socorro, NM 87801 USA. [Liu, Qingzhong; Sung, Andrew H.] New Mexico Inst Min & Technol, Inst Complex Addit Syst Anal, Socorro, NM 87801 USA. [Yang, Jack; Huang, Xudong] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02120 USA. [Yang, Jack; Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02120 USA. [Chen, Zhongxue] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Yang, Mary Qu] US DOE, Oak Ridge Natl Lab, Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. RP Sung, AH (reprint author), New Mexico Inst Min & Technol, Dept Comp Sci, Socorro, NM 87801 USA. EM liu@cs.nmt.edu; jyang@bwh.harvard.edu; zhongxuechen@gmail.com; yangma@mail.nih.gov; sung@cs.nmt.edu; xhuang3@partners.org RI Chen, Zhongxue/K-1372-2013 OI Chen, Zhongxue/0000-0003-2537-7843 NR 37 TC 5 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR S6 DI 10.1186/1471-2164-9-S1-S6 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100007 PM 18366619 ER PT J AU Pirooznia, M Gong, P Yang, JY Yang, MQ Perkins, EJ Deng, YP AF Pirooznia, Mehdi Gong, Ping Yang, Jack Y. Yang, Mary Qu Perkins, Edward J. Deng, Youping TI ILOOP - a web application for two-channel microarray interwoven loop design SO BMC GENOMICS LA English DT Article AB Microarray technology is widely applied to address complex scientific questions. However, there remain fundamental issues on how to design experiments to ensure that the resulting data enables robust statistical analysis. Interwoven loop design has several advantages over other designs. However it suffers in the complexity of design. We have implemented an online web application which allows users to find optimal loop designs for two-color microarray experiments. Given a number of conditions (such as treatments or time points) and replicates, the application will find the best possible design of the experiment and output experimental parameters. It is freely available from http://mcbc.usm.edu/iloop. C1 [Pirooznia, Mehdi; Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Gong, Ping] SpecPro Inc, Vicksburg, MS 39180 USA. [Yang, Jack Y.] Harvard Univ, Sch Med, Cambridge, MA 02140 USA. [Yang, Mary Qu] Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20852 USA. [Perkins, Edward J.] USA, Environm Lab, Engineer Res & Dev Ctr, Vicksburg, MS 39180 USA. RP Deng, YP (reprint author), Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. EM mehdi.pirooznia@usm.edu; Ping.Gong@erdc.usace.army.mil; jyang@bwh.harvard.edu; jyang@bwh.harvard.edu; Edward.J.Perkins@erdc.usace.army.mil; Youping.Deng@usm.edu OI Pirooznia, Mehdi/0000-0002-4210-6458 FU NCRR NIH HHS [2P20RR016476-04, P20 RR016476] NR 22 TC 5 Z9 6 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 2 AR S11 DI 10.1186/1471-2164-9-S2-S11 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JQ UT WOS:000206244200012 PM 18831776 ER PT J AU Pirooznia, M Yang, JY Yang, MQ Deng, YP AF Pirooznia, Mehdi Yang, Jack Y. Yang, Mary Qu Deng, Youping TI A comparative study of different machine learning methods on microarray gene expression data SO BMC GENOMICS LA English DT Article AB Background: Several classification and feature selection methods have been studied for the identification of differentially expressed genes in microarray data. Classification methods such as SVM, RBF Neural Nets, MLP Neural Nets, Bayesian, Decision Tree and Random Forrest methods have been used in recent studies. The accuracy of these methods has been calculated with validation methods such as v-fold validation. However there is lack of comparison between these methods to find a better framework for classification, clustering and analysis of microarray gene expression results. Results: In this study, we compared the efficiency of the classification methods including; SVM, RBF Neural Nets, MLP Neural Nets, Bayesian, Decision Tree and Random Forrest methods. The v-fold cross validation was used to calculate the accuracy of the classifiers. Some of the common clustering methods including K-means, DBC, and EM clustering were applied to the datasets and the efficiency of these methods have been analysed. Further the efficiency of the feature selection methods including support vector machine recursive feature elimination (SVM-RFE), Chi Squared, and CSF were compared. In each case these methods were applied to eight different binary (two class) microarray datasets. We evaluated the class prediction efficiency of each gene list in training and test cross-validation using supervised classifiers. Conclusions: We presented a study in which we compared some of the common used classification, clustering, and feature selection methods. We applied these methods to eight publicly available datasets, and compared how these methods performed in class prediction of test datasets. We reported that the choice of feature selection methods, the number of genes in the gene list, the number of cases (samples) substantially influence classification success. Based on features chosen by these methods, error rates and accuracy of several classification algorithms were obtained. Results revealed the importance of feature selection in accurately classifying new samples and how an integrated feature selection and classification algorithm is performing and is capable of identifying significant genes. C1 [Pirooznia, Mehdi; Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Yang, Jack Y.] Harvard Univ, Sch Med, Cambridge, MA 02140 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20852 USA. RP Deng, YP (reprint author), Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. EM mehdi.pirooznia@usm.edu; jyang@bwh.harvard.edu; yangma@mail.nih.gov; youping.deng@usm.edu OI Pirooznia, Mehdi/0000-0002-4210-6458 FU NCRR NIH HHS [P20 RR016476, 2P20RR016476-04] NR 40 TC 55 Z9 58 U1 3 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR S13 DI 10.1186/1471-2164-9-S1-S13 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100014 PM 18366602 ER PT J AU Yang, JY Yang, MQ Arabnia, HR Deng, YP AF Yang, Jack Y. Yang, Mary Qu Arabnia, Hamid R. Deng, Youping TI Genomics, molecular imaging, bioinformatics, and bio-nano-info integration are synergistic components of translational medicine and personalized healthcare research SO BMC GENOMICS LA English DT Editorial Material AB Supported by National Science Foundation (NSF), International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design and International Journal of Functional Informatics and Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more than 600 papers and 500 researchers and medical doctors. It was the only synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7 Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including 11 Special Research Interest Sessions that were designed dynamically at Harvard in response to the current research trends and advances. The committee was very grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice-President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Andy Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of Health) and other world-class scientific leaders. The Harvard meeting was a large academic event 100% full-sponsored by IEEE financially and academically. After a rigorous peer-review process, the committee selected 27 high-quality research papers from 600 submissions. The committee is grateful for contributions from keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on combining simulation and machine learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac? punumber=4425386) and Dr. Jack Y.Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2- 4, 2007, Silicon Valley, California, USA. C1 [Yang, Jack Y.] Harvard Univ, Sch Med, Cambridge, MA 02115 USA. [Yang, Mary Qu] Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20852 USA. [Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. RP Yang, JY (reprint author), Harvard Univ, Sch Med, POB 400888, Cambridge, MA 02115 USA. EM jyang@bwh.Harvard.edu; yangma@mail.nih.gov; hra@cs.uga.edu; youping.deng@usm.edu NR 38 TC 2 Z9 4 U1 0 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 2 AR I1 DI 10.1186/1471-2164-9-S2-I1 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JQ UT WOS:000206244200001 PM 18366597 ER PT J AU Yang, JY Yang, MQ Luo, ZJ Ma, Y Li, JL Deng, YP Huang, XD AF Yang, Jack Y. Yang, Mary Qu Luo, Zuojie Ma, Yan Li, Jianling Deng, Youping Huang, Xudong TI A hybrid machine learning-based method for classifying the Cushing's Syndrome with comorbid adrenocortical lesions SO BMC GENOMICS LA English DT Article AB Background: The prognosis for many cancers could be improved dramatically if they could be detected while still at the microscopic disease stage. It follows from a comprehensive statistical analysis that a number of antigens such as hTERT, PCNA and Ki-67 can be considered as cancer markers, while another set of antigens such as P27KIP1 and FHIT are possible markers for normal tissue. Because more than one marker must be considered to obtain a classification of cancer or no cancer, and if cancer, to classify it as malignant, borderline, or benign, we must develop an intelligent decision system that can fullfill such an unmet medical need. Results: We have developed an intelligent decision system using machine learning techniques and markers to characterize tissue as cancerous, non-cancerous or borderline. The system incorporates learning techniques such as variants of support vector machines, neural networks, decision trees, self-organizing feature maps (SOFM) and recursive maximum contrast trees (RMCT). These variants and algorithms we have developed, tend to detect microscopic pathological changes based on features derived from gene expression levels and metabolic profiles. We have also used immunohistochemistry techniques to measure the gene expression profiles from a number of antigens such as cyclin E, P27KIP1, FHIT, Ki-67, PCNA, Bax, Bcl-2, P53, Fas, FasL and hTERT in several particular types of neuroendocrine tumors such as pheochromocytomas, paragangliomas, and the adrenocortical carcinomas (ACC), adenomas (ACA), and hyperplasia (ACH) involved with Cushing's syndrome. We provided statistical evidence that higher expression levels of hTERT, PCNA and Ki-67 etc. are associated with a higher risk that the tumors are malignant or borderline as opposed to benign. We also investigated whether higher expression levels of P27KIP1 and FHIT, etc., are associated with a decreased risk of adrenomedullary tumors. While no significant difference was found between cell-arrest antigens such as P27KIP1 for malignant, borderline, and benign tumors, there was a significant difference between expression levels of such antigens in normal adrenal medulla samples and in adrenomedullary tumors. Conclusions: Our frame work focused on not only different classification schemes and feature selection algorithms, but also ensemble methods such as boosting and bagging in an effort to improve upon the accuracy of the individual classifiers. It is evident that when all sorts of machine learning and statistically learning techniques are combined appropriately into one integrated intelligent medical decision system, the prediction power can be enhanced significantly. This research has many potential applications; it might provide an alternative diagnostic tool and a better understanding of the mechanisms involved in malignant transformation as well as information that is useful for treatment planning and cancer prevention. C1 [Yang, Jack Y.; Huang, Xudong] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Yang, Mary Qu] NHGRI, Genom Funct Anal Lab, NIH, US Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Luo, Zuojie; Ma, Yan; Li, Jianling] Guangxi Med Univ, Affiliated Hosp 1, Dept Endocrinol, Nanning 530021, Guangxi, Peoples R China. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. RP Luo, ZJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. EM jyang@bwh.harvard.edu; yangma@mail.nih.gov; zluo888@yahoo.com.cn; youping.deng@usm.edu; xhuang3@partners.org NR 111 TC 2 Z9 4 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR S23 DI 10.1186/1471-2164-9-S1-S23 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100024 PM 18366613 ER PT J AU Yang, JY Li, GZ Meng, HH Yang, MQ Deng, YP AF Yang, Jack Y. Li, Guo-Zheng Meng, Hao-Hua Yang, Mary Qu Deng, Youping TI Improving prediction accuracy of tumor classification by reusing genes discarded during gene selection SO BMC GENOMICS LA English DT Article AB Background: Since the high dimensionality of gene expression microarray data sets degrades the generalization performance of classifiers, feature selection, which selects relevant features and discards irrelevant and redundant features, has been widely used in the bioinformatics field. Multitask learning is a novel technique to improve prediction accuracy of tumor classification by using information contained in such discarded redundant features, but which features should be discarded or used as input or output remains an open issue. Results: We demonstrate a framework for automatically selecting features to be input, output, and discarded by using a genetic algorithm, and propose two algorithms: GA-MTL (Genetic algorithm based multi-task learning) and e-GA-MTL (an enhanced version of GA-MTL). Experimental results demonstrate that this framework is effective at selecting features for multitask learning, and that GA-MTL and e-GA-MTL perform better than other heuristic methods. Conclusions: Genetic algorithms are a powerful technique to select features for multi-task learning automatically; GA-MTL and e-GA-MTL are shown to to improve generalization performance of classifiers on microarray data sets. C1 [Li, Guo-Zheng; Meng, Hao-Hua] Shanghai Univ, Sch Engn & Comp Sci, Shanghai 200072, Peoples R China. [Yang, Jack Y.] Harvard Univ, Sch Med, Cambridge, MA 02140 USA. [Li, Guo-Zheng] Shanghai Univ, Inst Syst Biol, Shanghai 200072, Peoples R China. [Yang, Mary Qu] NHGRI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. RP Li, GZ (reprint author), Shanghai Univ, Sch Engn & Comp Sci, Shanghai 200072, Peoples R China. EM jyang@bwh.harvard.edu; gzli@shu.edu.cn; mhhtj@shu.edu.cn; yangma@mail.nih.gov; youping.deng@usm.edu RI Li, Guo-Zheng /D-5744-2011 OI Li, Guo-Zheng /0000-0001-5568-0347 NR 23 TC 6 Z9 7 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR S3 DI 10.1186/1471-2164-9-S1-S3 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100004 PM 18366616 ER PT J AU Yang, JY Yang, MQ Zhu, M Arabnia, HR Deng, YP AF Yang, Jack Y. Yang, Mary Qu Zhu, Mengxia (Michelle) Arabnia, Hamid R. Deng, Youping TI Promoting synergistic research and education in genomics and bioinformatics SO BMC GENOMICS LA English DT Article AB Bioinformatics and Genomics are closely related disciplines that hold great promises for the advancement of research and development in complex biomedical systems, as well as public health, drug design, comparative genomics, personalized medicine and so on. Research and development in these two important areas are impacting the science and technology. High throughput sequencing and molecular imaging technologies marked the beginning of a new era for modern translational medicine and personalized healthcare. The impact of having the human sequence and personalized digital images in hand has also created tremendous demands of developing powerful supercomputing, statistical learning and artificial intelligence approaches to handle the massive bioinformatics and personalized healthcare data, which will obviously have a profound effect on how biomedical research will be conducted toward the improvement of human health and prolonging of human life in the future. The International Society of Intelligent Biological Medicine (http://www.isibm.org) and its official journals, the International Journal of Functional Informatics and Personalized Medicine (http://www.inderscience.com/ijfipm) and the International Journal of Computational Biology and Drug Design (http://www.inderscience.com/ijcbdd) in collaboration with International Conference on Bioinformatics and Computational Biology (Biocomp), touch tomorrow's bioinformatics and personalized medicine throughout today's efforts in promoting the research, education and awareness of the upcoming integrated inter/multidisciplinary field. The 2007 international conference on Bioinformatics and Computational Biology (BIOCOMP07) was held in Las Vegas, the United States of American on June 25-28, 2007. The conference attracted over 400 papers, covering broad research areas in the genomics, biomedicine and bioinformatics. The Biocomp 2007 provides a common platform for the cross fertilization of ideas, and to help shape knowledge and scientific achievements by bridging these two very important disciplines into an interactive and attractive forum. Keeping this objective in mind, Biocomp 2007 aims to promote interdisciplinary and multidisciplinary education and research. 25 high quality peer-reviewed papers were selected from 400+ submissions for this supplementary issue of BMC Genomics. Those papers contributed to a wide-range of important research fields including gene expression data analysis and applications, high-throughput genome mapping, sequence analysis, gene regulation, protein structure prediction, disease prediction by machine learning techniques, systems biology, database and biological software development. We always encourage participants submitting proposals for genomics sessions, special interest research sessions, workshops and tutorials to Professor Hamid R. Arabnia (hra@cs.uga.edu) in order to ensure that Biocomp continuously plays the leadership role in promoting inter/multidisciplinary research and education in the fields. Biocomp received top conference ranking with a high score of 0.95/1.00. Biocomp is academically cosponsored by the International Society of Intelligent Biological Medicine and the Research Laboratories and Centers of Harvard University - Massachusetts Institute of Technology, Indiana University - Purdue University, Georgia Tech Emory University, UIUC, UCLA, Columbia University, University of Texas at Austin and University of Iowa etc. Biocomp - Worldcomp brings leading scientists together across the nation and all over the world and aims to promote synergistic components such as keynote lectures, special interest sessions, workshops and tutorials in response to the advances of cutting-edge research. C1 [Yang, Jack Y.] Harvard Univ, Cambridge, MA 02140 USA. [Yang, Mary Qu] NHGRI, NIH, US Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Zhu, Mengxia (Michelle)] So Illinois Univ, Dept Comp Sci, Carbondale, IL 62901 USA. [Arabnia, Hamid R.] Univ Georgia, Dept Comp Sci, Athens, GA 30602 USA. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. RP Yang, JY (reprint author), Harvard Univ, POB 400888, Cambridge, MA 02140 USA. EM jyang@bwh.harvard.edu; yangma@mail.nih.gov; mzhu@cs.siu.edu; hra@cs.uga.edu; youping.deng@usm.edu NR 25 TC 9 Z9 9 U1 3 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR 11 DI 10.1186/1471-2164-9-S1-11 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100001 ER PT J AU Yang, JY Niemierko, A Yang, MQ Deng, YP AF Yang, Jack Y. Niemierko, Andrzej Yang, Mary Qu Deng, Youping TI Analyzing adjuvant radiotherapy suggests a non monotonic radio-sensitivity over tumor volumes SO BMC GENOMICS LA English DT Article AB Background: Adjuvant Radiotherapy (RT) after surgical removal of tumors proved beneficial in long-term tumor control and treatment planning. For many years, it has been well concluded that radio-sensitivities of tumors upon radiotherapy decrease according to the sizes of tumors and RT models based on Poisson statistics have been used extensively to validate clinical data. Results: We found that Poisson statistics on RT is actually derived from bacterial cells despite of many validations from clinical data. However cancerous cells do have abnormal cellular communications and use chemical messengers to signal both surrounding normal and cancerous cells to develop new blood vessels and to invade, to metastasis and to overcome intercellular spatial confinements in general. We therefore investigated the cell killing effects on adjuvant RT and found that radio-sensitivity is actually not a monotonic function of volume as it was believed before. We present detailed analysis and explanation to justify above statement. Based on EUD, we present an equivalent radio-sensitivity model. Conclusion: We conclude that radio sensitivity is a sophisticated function over tumor volumes, since tumor responses upon radio therapy also depend on cellular communications. C1 [Yang, Jack Y.; Niemierko, Andrzej] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Yang, Jack Y.; Niemierko, Andrzej] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Yang, Mary Qu] Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20852 USA. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Bioinformat & Canc Biol Lab, Hattiesburg, MS 39406 USA. RP Niemierko, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jyang@bwh.harvard.edu; aniemierko@partners.org; yangma@mail.NIH.gov; youping.deng@usm.edu FU NCI NIH HHS [R01 CA50628, R01 CA050628] NR 16 TC 2 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 2 AR S9 DI 10.1186/1471-2164-9-S2-S9 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JQ UT WOS:000206244200010 PM 18831800 ER PT J AU Yang, JY Yang, MQ Dunker, KA Deng, YP Huang, XD AF Yang, Jack Y. Yang, Mary Qu Dunker, Keith A. Deng, Youping Huang, Xudong TI Investigation of transmembrane proteins using a computational approach SO BMC GENOMICS LA English DT Article AB Background: An important subfamily of membrane proteins are the transmembrane a-helical proteins, in which the membrane-spanning regions are made up of a-helices. Given the obvious biological and medical significance of these proteins, it is of tremendous practical importance to identify the location of transmembrane segments. The difficulty of inferring the secondary or tertiary structure of transmembrane proteins using experimental techniques has led to a surge of interest in applying techniques from machine learning and bioinformatic stoinfer secondary structure from primary structure in these proteins. We are therefore interested in determining which physicochemical properties are most useful for discriminating transmembrane segments from non-transmembrane segments in transmembrane proteins, and for discriminating intrinsically unstructured segments from intrinsically structured segments in transmembrane proteins, and in using the results of these investigations to develop classifiers to identify transmembrane segments in transmembrane proteins. Results: We determined that the most useful properties for discriminating transmembrane segments from non-transmembrane segments and for discriminating intrinsically unstructured segments from intrinsically structured segments in transmembrane proteins were hydropathy, polarity, and flexibility, and used the results of this analysis to construct classifiers to discriminate transmembrane segments from non-transmembrane segments using four classification techniques: two variants of the Self-Organizing Global Ranking algorithm, a decision tree algorithm, and a support vector machine algorithm. All four techniques exhibited good performance, with out-of-sample accuracies of approximately 75%. Conclusions: Several interesting observations emerged from our study: intrinsically unstructured segments and transmembrane segments tend to have opposite properties; transmembrane proteins appear to be much richer in intrinsically unstructured segments than other proteins; and, in approximately 70% of transmembrane proteins that contain intrinsically unstructured segments, the intrinsically unstructured segments are close to transmembrane segments. C1 [Yang, Jack Y.; Huang, Xudong] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Deng, Youping] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. [Yang, Jack Y.; Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yang, Mary Qu] NHGRI, NIH, Bethesda, MD 20892 USA. [Dunker, Keith A.] Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Dunker, Keith A.] Indiana Univ, Sch Informat, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. RP Deng, YP (reprint author), Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA. EM jyang@bwh.harvard.edu; yangma@mail.nih.gov; kedunker@iupui.edu; youping.deng@usm.edu; xhuang3@partners.org NR 40 TC 10 Z9 11 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR S7 DI 10.1186/1471-2164-9-S1-S7 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100008 PM 18366620 ER PT J AU Yang, MQ Elnitski, L AF Yang, Mary Qu Elnitski, Laura TI Prediction-based approaches to characterize bidirectional promoters in the mammalian genome SO BMC GENOMICS LA English DT Article AB Background: Machine learning approaches are emerging as a way to discriminate various classes of functional elements. Previous attempts to create Regulatory Potential ( RP) scores to discriminate functional DNA from nonfunctional DNA included using Markov models trained to identify sequences from promoters and enhancers from ancestral repeats. We proposed that knowledge gleaned from those methods could be further refined using a multiple class predictor to separate classes of promoter elements from enhancers or nonfunctional DNA. Results: We extended our previous work, which identified over 5,000 candidate bidirectional promoters in the human genome, to map the orthologous promoter regions in the mouse genome. Our algorithm measured the robustness of evidence provided by the spliced EST annotations and incorporated evidence from annotations of UCSC Known Genes and GenBank mRNA. In preparation for de novo prediction of this promoter type, we examined characteristic features of the dataset as a whole. For instance, bidirectional promoters score very highly among all functional elements for Regulatory Potential Scores. This result was unexpected due to the limited sequence conservation found in these noncoding regions. We demonstrate that bidirectional promoters can be classified apart from other genomic features including non-bidirectional promoters, i. e. those promoters having no nearby upstream genes. Furthermore bidirectional promoters consistently score at the level of very highly conserved functional elements in the genome-developmental enhancers. The high scores are due to sequence- based characteristics within the promoters, not the surrounding exons. These results indicate that high-scoring RP regions can be deconvoluted into various functional classes of genomic elements. Using a multiple class predictor we are able to discriminate bidirectional promoters from enhancers, non-bidirectional promoters, and non-promoter regions on the basis of RP scores and CpG islands. Conclusions: We examine orthology at bidirectional promoters, use discriminatory machine learning approaches to differentiate multiple types of promoters from other functional and nonfunctional features in the genome and begin the process of deconvoluting classes of functional regions that score well with RP scores. These types of approaches precede supervised learning techniques to discover unannotated promoter regions. C1 [Yang, Mary Qu; Elnitski, Laura] NHGRI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Elnitski, L (reprint author), NHGRI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM yangma@mail.nih.gov; elnitski@mail.nih.gov FU Intramural NIH HHS NR 14 TC 11 Z9 13 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 1 AR S2 DI 10.1186/1471-2164-9-S1-S2 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JP UT WOS:000206244100003 PM 18366609 ER PT J AU Yang, MQ Elnitski, L AF Yang, Mary Qu Elnitski, Laura TI Diversity of core promoter elements comprising human bidirectional promoters SO BMC GENOMICS LA English DT Article AB Background: Bidirectional promoters lie between adjacent genes, which are transcribed from opposite strands of DNA. The functional mechanisms underlying the activation of bidirectional promoters are currently uncharacterised. To define the core promoter elements of bidirectional promoters in human, we mapped motifs for TATA, INR, BRE, DPE, INR, as well as CpG-islands. Results: We found a consistently high correspondence between C+G content, CpG-island presence and an average expression level increasing the median level for all genes in bidirectional promoters. These CpG-rich promoters showed discrete initiation patterns rather than broad regions of transcription initiation, as are typically seen for CpG-island promoters. CpG-islands encompass both TSSs within bidirectional promoters, providing an explanation for the symmetrical co-expression patterns of many of these genes. In contrast, TATA motifs appear to be asymmetrically positioned at one TSS or the other. Conclusion: Our findings demonstrate that bidirectional promoters utilize a variety of core promoter elements to initiate transcription. CpG-islands dominate the regulatory landscape of this group of promoters. C1 [Yang, Mary Qu; Elnitski, Laura] Natl Human Genome Res Inst, Natl Inst Hlth, Rockville, MD 20852 USA. RP Elnitski, L (reprint author), Natl Human Genome Res Inst, Natl Inst Hlth, Rockville, MD 20852 USA. EM yangma@mail.nih.gov; elnitski@mail.nih.gov FU Intramural NIH HHS NR 15 TC 36 Z9 40 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 2 AR S3 DI 10.1186/1471-2164-9-S2-S3 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JQ UT WOS:000206244200004 PM 18831794 ER PT J AU Locatis, C Vega, A Bhagwat, M Liu, WL Conde, J AF Locatis, Craig Vega, Anibal Bhagwat, Medha Liu, Wei-Li Conde, Jose TI A virtual computer lab for distance biomedical technology education SO BMC MEDICAL EDUCATION LA English DT Article AB Background: The National Library of Medicine's National Center for Biotechnology Information offers mini-courses which entail applying concepts in biochemistry and genetics to search genomics databases and other information sources. They are highly interactive and involve use of 3D molecular visualization software that can be computationally taxing. Methods: Methods were devised to offer the courses at a distance so as to provide as much functionality of a computer lab as possible, the venue where they are normally taught. The methods, which can be employed with varied videoconferencing technology and desktop sharing software, were used to deliver mini-courses at a distance in pilot applications where students could see demonstrations by the instructor and the instructor could observe and interact with students working at their remote desktops. Results: Student ratings of the learning experience and comments to open ended questions were similar to those when the courses are offered face to face. The real time interaction and the instructor's ability to access student desktops from a distance in order to provide individual assistance and feedback were considered invaluable. Conclusion: The technologies and methods mimic much of the functionality of computer labs and may be usefully applied in any context where content changes frequently, training needs to be offered on complex computer applications at a distance in real time, and where it is necessary for the instructor to monitor students as they work. C1 [Locatis, Craig; Liu, Wei-Li] Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD USA. [Vega, Anibal; Conde, Jose] Univ Puerto Rico, Ctr Informat Architecture Res, San Juan, PR 00936 USA. [Bhagwat, Medha] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Locatis, C (reprint author), Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD USA. EM locatis@nlm.nih.gov; avega@rcm.upr.edu; bhagwat@ncbi.nlm.nih.gov; wliu@mail.nih.gov; jconde@rcm.upr.edu FU National Center for Research Resources (NCRR) [G12RR03051]; NIH FX AV and JC's contributions were supported through funding provided by Grant Number G12RR03051(RCMI Program, University of Puerto Rico Medical Sciences Campus) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). CL, MB, WL contributions were supported by NIH intramural research. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. NR 23 TC 4 Z9 5 U1 3 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6920 J9 BMC MED EDUC JI BMC Med. Educ. PY 2008 VL 8 AR 12 DI 10.1186/1472-6920-8-12 PG 8 WC Education & Educational Research; Education, Scientific Disciplines SC Education & Educational Research GA V14LE UT WOS:000207735100012 PM 18366629 ER PT J AU Blauwkamp, MN Yu, JC Schin, MA Burke, KA Berry, MJ Carlson, BA Brosius, FC Koenig, RJ AF Blauwkamp, Marsha N. Yu, Jingcheng Schin, MaryLee A. Burke, Kathleen A. Berry, Marla J. Carlson, Bradley A. Brosius, Frank C., III Koenig, Ronald J. TI Podocyte specific knock out of selenoproteins does not enhance nephropathy in streptozotocin diabetic C57BL/6 mice SO BMC NEPHROLOGY LA English DT Article AB Background: Selenoproteins contain selenocysteine (Sec), commonly considered the 21(st) genetically encoded amino acid. Many selenoproteins, such as the glutathione peroxidases and thioredoxin reductases, protect cells against oxidative stress by functioning as antioxidants and/or through their roles in the maintenance of intracellular redox balance. Since oxidative stress has been implicated in the pathogenesis of diabetic nephropathy, we hypothesized that selenoproteins protect against this complication of diabetes. Methods: C57BL/6 mice that have a podocyte-specific inability to incorporate Sec into proteins (denoted in this paper as PodoTrsp(-/-)) and control mice were made diabetic by intraperitoneal injection of streptozotocin, or were injected with vehicle. Blood glucose, body weight, microalbuminuria, glomerular mesangial matrix expansion, and immunohistochemical markers of oxidative stress were assessed. Results: After 3 and 6 months of diabetes, control and PodoTrsp(-/-) mice had similar levels of blood glucose. There were no differences in urinary albumin/creatinine ratios. Periodic acid-Schiff staining to examine mesangial matrix expansion also demonstrated no difference between control and PodoTrsp(-/-) mice after 6 months of diabetes, and there were no differences in immunohistochemical stainings for nitrotyrosine or NAD(P) H dehydrogenase, quinone 1. Conclusion: Loss of podocyte selenoproteins in streptozotocin diabetic C57BL/6 mice does not lead to increased oxidative stress as assessed by nitrotyrosine and NAD(P) H dehydrogenase, quinone 1 immunostaining, nor does it lead to worsening nephropathy. C1 [Blauwkamp, Marsha N.; Yu, Jingcheng; Koenig, Ronald J.] Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. [Blauwkamp, Marsha N.; Koenig, Ronald J.] Univ Michigan, Cell & Mol Biol Grad Program, Ann Arbor, MI 48109 USA. [Schin, MaryLee A.; Burke, Kathleen A.; Brosius, Frank C., III] Univ Michigan, Div Nephrol, Ann Arbor, MI 48109 USA. [Berry, Marla J.] Univ Hawaii Manoa, Dept Cell & Mol Biol, Honolulu, HI 96813 USA. [Carlson, Bradley A.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Koenig, RJ (reprint author), Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. EM mousman@umich.edu; jingyu@umich.edu; mschin@umich.edu; kathleen_burke@brown.edu; mberry@hawaii.edu; carlsonb@mail.nih.gov; fbrosius@umich.edu; rkoenig@umich.edu FU Pilot and Feasibility; Cell and Molecular Biology Core of the Michigan Diabetes Research and Training Center (NIH) [P60 DK020572] FX We thank Dr. L. B. Holzman for providing the podocin-Cre mice. This work was supported by a Pilot and Feasibility grant and the Cell and Molecular Biology Core of the Michigan Diabetes Research and Training Center (NIH P60 DK020572). NR 22 TC 11 Z9 11 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2369 J9 BMC NEPHROL JI BMC Nephrol. PY 2008 VL 9 AR 7 DI 10.1186/1471-2369-9-7 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA V13KC UT WOS:000207664700007 PM 18647412 ER PT S AU Krushkal, J Puljic, M Yan, B Barbe, JF Mahadevan, R Postier, B O'Neil, RA Reguera, G Leang, C DiDonato, LN Nunez, C Methe, BA Adkins, RM Lovley, DR AF Krushkal, Julia Puljic, Marko Yan, Bin Barbe, Jose F. Mahadevan, Radhakrishnan Postier, Bradley O'Neil, Regina A. Reguera, Gemma Leang, Ching DiDonato, Laurie N. Nunez, Cinthia Methe, Barbara A. Adkins, Ronald M. Lovley, Derek R. GP IEEE TI Genome regions involved in multiple regulatory pathways identified using GSEL, a genome-wide database of regulatory sequence elements of Geobacter sulfurreducens SO BMEI 2008: PROCEEDINGS OF THE INTERNATIONAL CONFERENCE ON BIOMEDICAL ENGINEERING AND INFORMATICS, VOL 1 SE International Conference on Biomedical Engineering and Informatics LA English DT Proceedings Paper CT 1st International Conference on Biomedical Engineering and Informatics CY MAY 27-30, 2008 CL Sanya, PEOPLES R CHINA SP Tianjin Univ Technol, IEEE Comp Soc ID ESCHERICHIA-COLI; GENE-EXPRESSION; REDUCTION; FE(III); SITES; RPOS AB Organisms from the metal-reducing family Geobacteraceae participate in bioremediation of contaminated environments and in energy harvesting. We have developed a database and an accompanying online query system, GSEL, for Geobacter Sequence Elements (available from http://www.geobacter.org/research/gsel/). It compiles information on predicted transcription regulatory elements in the genome of G. sulfurreducens. These elements were derived from analyses that employed genome-wide transcription profiling, comparative genomics, and similarity searches. Clustering was employed to group overlapping sequence elements with similar genome locations. Subsequent scoring and sorting allowed us to identify individual sequence elements and regulatory clusters that were predicted by the highest number of independent microarray gene expression and sequence comparison data sets. These sequence elements and genome regions are likely to be involved in gene regulation under a variety of conditions or in multiple biological pathways. C1 [Krushkal, Julia; Puljic, Marko; Yan, Bin; Barbe, Jose F.; Adkins, Ronald M.] Univ Tennessee, Ctr Hlth Sci, 66 N Pauline,Ste 633, Memphis, TN 38163 USA. [Yan, Bin] Natl Inst Hlth, NIDCD, Bethesda, MD USA. [Mahadevan, Radhakrishnan] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Postier, Bradley; O'Neil, Regina A.; Reguera, Gemma; Leang, Ching; DiDonato, Laurie N.; Nunez, Cinthia; Lovley, Derek R.] Univ Massachusetts, Amherst, MA 01003 USA. [Postier, Bradley] Washington Univ, St Louis, MO 63130 USA. [Reguera, Gemma] Michigan State Univ, E Lansing, MI 48824 USA. [Nunez, Cinthia] UNAM, Inst Biotechnol, Cuernavaca, Morelos, Mexico. [Methe, Barbara A.] J Craig Venter Inst, Rockville, MD USA. RP Krushkal, J (reprint author), Univ Tennessee, Ctr Hlth Sci, 66 N Pauline,Ste 633, Memphis, TN 38163 USA. EM jkrushka@utmem.edu RI Mahadevan, Radhakrishnan/A-8502-2008 OI Mahadevan, Radhakrishnan/0000-0002-1270-9063 FU Office of Science (BER), U.S. Department of Energy [DE-FC02-02ER63446] FX This research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FC02-02ER63446. NR 19 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 SN 1948-2914 BN 978-0-7695-3118-2 J9 INT CONF BIOMED PY 2008 BP 424 EP + DI 10.1109/BMEI.2008.226 PG 3 WC Engineering, Biomedical; Mathematical & Computational Biology SC Engineering; Mathematical & Computational Biology GA BHW79 UT WOS:000257096000081 ER PT J AU Choi, SJ Song, IS Ryu, OH Choi, SW Hart, PS Wu, WW Shen, RF Hart, TC AF Choi, Sun Jin Song, In Sun Ryu, Ok Hee Choi, Sung Won Hart, P. Suzanne Wu, Wells W. Shen, Rong-Fong Hart, Thomas C. TI A 4 bp deletion mutation in DLX3 enhances osteoblastic differentiation and bone formation in vitro SO BONE LA English DT Article DE Distal-less 3; Tricho-Dento-Osseous syndrome; osteoblast differentiation; osteocalcin; collagen ID TRICHODENTOOSSEOUS SYNDROME; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVITY; MORPHOGENETIC PROTEIN-2; CLINICAL HETEROGENEITY; VERTEBRATE DEVELOPMENT; CELL-DIFFERENTIATION; MOUSE KERATINOCYTES; MATRIX PROTEINS; HOMEOBOX GENES AB A 4 base-pair deletion mutation in the Distal-less 3 (DLX3) gene is etiologic for Tricho-Dento-Osseous syndrome (TDO). A cardinal feature of TDO is an increased thickness and density of bone. We tested the effects of the DLX3 gene mutation responsible for TDO on the osteoblastic differentiation of preosteoblastic MC3T3E1 cells and multipontent mesenchymal C2C12 cells. Differential expression analysis of C2C12 cells transfected with wild type DLX3 or mutant DLX3 was performed and desmin gene expression, an early myoblastic differentiation marker in mesenchymal cells, was evaluated by RT-PCR, western blot analysis, and desmin promoter transcriptional activity. Transfection of wild type DLX3 into MC3T3E1 and C2C12 cells increased alkaline phosphatase-2 activity, mineral deposition, and promoter activities of the osteocalcin and type I collagen genes compared to empty vector transfected cells. Transfection of mutant DLX3 into these cells further enhanced alkaline phosphatase activity, mineral deposition, and osteocalcin promoter activities, but did not further enhance type I collagen promoter activity. Transfection of mutant DLX3 into C2C12 cells markedly down regulated desmin gene expression, and protein expression of desmin and MyoD, while increasing protein expression of osterix and Runx2. These results demonstrate that the DLX3 deletion mutation associated with TDO enhances mesenchymal cell differentiation to an osteoblastic lineage rather than a myoblastic lineage by changing the fate of mesenchymal cells. This DLX3 mutation also accelerates the differentiation of osteoprogenitor cells to osteoblasts at later stages of osteogenesis. Published by Elsevier Inc. C1 [Choi, Sun Jin; Song, In Sun; Ryu, Ok Hee; Choi, Sung Won; Hart, Thomas C.] Natl Inst Dent & Craniofacial Res, Human Craniofacial Genet Sect, NIH, Bethesda, MD 20892 USA. [Hart, P. Suzanne] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Wu, Wells W.; Shen, Rong-Fong] NHLBI, Proteo Core Facil, NIH, Bethesda, MD 20892 USA. RP Hart, TC (reprint author), 10 Ctr Dr,Bldg 10,Room 5-2531, Bethesda, MD 20892 USA. EM thart@mail.nih.gov FU Intramural NIH HHS [Z01 DE000711-04] NR 38 TC 17 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JAN PY 2008 VL 42 IS 1 BP 162 EP 171 DI 10.1016/j.bone.2007.08.047 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KW UT WOS:000252518100019 PM 17950683 ER PT J AU Schuck-Paim, C Alonso, WJ Ottoni, EB AF Schuck-Paim, Cynthia Alonso, Wladimir J. Ottoni, Eduardo B. TI Cognition in an ever-changing world: Climatic variability is associated with brain size in neotropical parrots SO BRAIN BEHAVIOR AND EVOLUTION LA English DT Review DE brain size; cognitive ability; encephalization; intelligence; climate; environmental variability; behavioral flexibility; parrots ID PHYLOGENETICALLY INDEPENDENT CONTRASTS; FOREBRAIN SIZE; HISTORICAL BIOGEOGRAPHY; BEHAVIORAL FLEXIBILITY; MOLECULAR SYSTEMATICS; CONFIDENCE-INTERVALS; DEVELOPMENTAL RATES; INVASION SUCCESS; INNOVATION RATE; NEST PREDATION AB Research on the conditions favoring the evolution of complex cognition and its underlying neural structures has increasingly stressed the role of environmental variability. These studies suggest that the ability to learn, behave flexibly and innovate would be favored under unpredictable variations in the availability of resources, as it would enable organisms to adjust to novel conditions. Despite the growing number of studies based on the idea that larger-brained organisms would be better prepared to cope with environmental challenges, direct testing of the association between brain size and environmental variability per se remains scant. Here we focus on Neotropical parrots as our model group and test the hypothesis that if relatively larger brains were favored in climatically variable environments, larger-brained species should currently tolerate a higher degree of environmental uncertainty. Although we show that there are also other factors underlying the dynamics of brain size variation in this group, our results support the hypothesis that proportionally larger-brained species are more tolerant to climatic variability, both on a temporal and spatial scale. Additionally, they suggest that the differences in relative brain size among Neotropical parrots represent multiple, recent events in the evolutionary history of the group, and are particularly tied to an increased dependence on more open and climatically unstable habitats. As this is the first study to present evidence of the link between brain size and climatic variability in birds, our findings provide a step towards understanding the potential benefits underlying variation in brain size and the maintenance of highly enlarged brains in this and other groups. Copyright (C) 2008 S. Karger AG, Basel. C1 [Schuck-Paim, Cynthia; Ottoni, Eduardo B.] Univ Sao Paulo, Inst Psychol, Dept Expt Psychol, Lab Cognit Ethol, BR-01455010 Sao Paulo, Brazil. [Alonso, Wladimir J.] NIH, Fogarty Int Ctr, Bethesda, MD USA. RP Schuck-Paim, C (reprint author), Univ Sao Paulo, Inst Psychol, Dept Expt Psychol, Lab Cognit Ethol, R Tucuma 141-A102, BR-01455010 Sao Paulo, Brazil. EM cynthia@origem.info RI Ottoni, Eduardo/E-4941-2012 OI Ottoni, Eduardo/0000-0003-1288-8345 NR 113 TC 33 Z9 35 U1 6 U2 49 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-8977 J9 BRAIN BEHAV EVOLUT JI Brain Behav. Evol. PY 2008 VL 71 IS 3 BP 200 EP 215 DI 10.1159/000119710 PG 16 WC Behavioral Sciences; Neurosciences; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Zoology GA 289XQ UT WOS:000255087600004 PM 18322361 ER PT J AU Ahmed, S Maranian, M Gregory, CS Udler, M Field, HI Tyrer, J Hesketh, R Metcalfe, JC Scollen, S Stuewing, JP Ponder, BAJ Pharoah, PDP Easton, DF Dunning, AM AF Ahmed, S. Maranian, M. Gregory, C. S. Udler, M. Field, H. I. Tyrer, J. Hesketh, R. Metcalfe, J. C. Scollen, S. Stuewing, J. P. Ponder, B. A. J. Pharoah, P. D. P. Easton, D. F. Dunning, A. M. TI From association to cause: fine mapping of the TNRC9 gene region, a novel susceptibility locus identified in the first genome-wide association study for breast cancer SO BREAST CANCER RESEARCH LA English DT Meeting Abstract CT Breast Cancer Research Meeting CY MAY 13, 2008 CL London, ENGLAND SP Royal Soc C1 [Ahmed, S.; Maranian, M.; Gregory, C. S.; Udler, M.; Field, H. I.; Tyrer, J.; Ponder, B. A. J.; Pharoah, P. D. P.; Dunning, A. M.] Univ Cambridge, Canc Res UK, Dept Oncol, Strangeways Res Lab, Cambridge, England. [Hesketh, R.; Metcalfe, J. C.; Scollen, S.] Univ Cambridge, Dept Biochem, Cambridge CB2 1TN, England. [Stuewing, J. P.] US Natl Canc Inst, Lab Populat Genet, Bethesda, MD USA. [Easton, D. F.] Univ Cambridge, Strangeways Res Lab, Genet Epidemiol Unit, Dept Publ Hlth & Primary Care,Canc Res UK, Cambridge, England. NR 2 TC 1 Z9 1 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 SU 2 MA P49 BP S26 EP S26 AR P49 DI 10.1186/bcr1933 PG 1 WC Oncology SC Oncology GA 302BI UT WOS:000255940900055 ER PT J AU Mendez-Catala, CF Cherhukhin, I Docquier, F Farrar, D Pugacheva, E Vostrov, A Klenova, E AF Mendez-Catala, C. F. Cherhukhin, I. Docquier, F. Farrar, D. Pugacheva, E. Vostrov, A. Klenova, E. TI Investigation into the molecular mechanism of the antiapoptotic functions of CTCF in breast cancer cells using a proteomics approach SO BREAST CANCER RESEARCH LA English DT Meeting Abstract CT Breast Cancer Research Meeting CY MAY 13, 2008 CL London, ENGLAND SP Royal Soc C1 [Mendez-Catala, C. F.; Cherhukhin, I.; Docquier, F.; Farrar, D.; Klenova, E.] Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. [Pugacheva, E.; Vostrov, A.] NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 SU 2 MA P19 BP S12 EP S12 DI 10.1186/bcr1903 PG 1 WC Oncology SC Oncology GA 302BI UT WOS:000255940900026 ER PT J AU Azzato, EM Driver, KE Lesueur, F Shah, M Greenberg, D Easton, DF Teschendorff, AE Caldas, C Caporaso, NE Pharoah, PDP AF Azzato, Elizabeth M. Driver, Kristy E. Lesueur, Fabienne Shah, Mitul Greenberg, David Easton, Douglas F. Teschendorff, Andrew E. Caldas, Carlos Caporaso, Neil E. Pharoah, Paul D. P. TI Effects of common germline genetic variation in cell cycle control genes on breast cancer survival: results from a population-based cohort SO BREAST CANCER RESEARCH LA English DT Article ID PEPSINOGEN-C; EXPRESSION; ASSOCIATION; PROTEIN; TUMORS; IDENTIFICATION; PROGNOSIS; MARKERS; CCND1 AB Introduction Somatic alterations have been shown to correlate with breast cancer prognosis and survival, but less is known about the effects of common inherited genetic variation. Of particular interest are genes involved in cell cycle pathways, which regulate cell division. Methods We examined associations between common germline genetic variation in 13 genes involved in cell cycle control (CCND1, CCND2, CCND3, CCNE1, CDK2 [p33], CDK4, CDK6, CDKN1A [p21, Cip1], CDKN1B [p27, Kip1], CDKN2A [p16], CDKN2B [p15], CDKN2C [p18], and CDKN2D [p19]) and survival among women diagnosed with invasive breast cancer participating in the SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity) breast cancer study. DNA from up to 4,470 women was genotyped for 85 polymorphisms that tag the known common polymorphisms (minor allele frequency > 0.05) in the genes. The genotypes of each polymorphism were tested for association with survival using Cox regression analysis. Results The rare allele of the tagging single nucleotide polymorphism (SNP) rs2479717 is associated with an increased risk of death (hazard ratio = 1.26 per rare allele carried, 95% confidence interval: 1.12 to 1.42; P = 0.0001), which was not attenuated after adjusting for tumour stage, grade, and treatment. This SNP is part of a large linkage disequilibrium block, which contains CCND3, BYSL, TRFP, USP49, C6ofr49, FRS3, and PGC. We evaluated the association of survival and somatic expression of these genes in breast tumours using expression microarray data from seven published datasets. Elevated expression of the C6orf49 transcript was associated with breast cancer survival, adding biological interest to the finding. Conclusion It is possible that CCND3 rs2479717, or another variant it tags, is associated with prognosis after a diagnosis of breast cancer. Further study is required to validate this finding. C1 [Azzato, Elizabeth M.; Driver, Kristy E.; Lesueur, Fabienne; Shah, Mitul; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England. [Azzato, Elizabeth M.; Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Greenberg, David] Eastern Canc Registrat & Informat Ctr, Unit C Magog Court, Cambridge CB22 3AD, England. [Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 8RN, England. [Teschendorff, Andrew E.; Caldas, Carlos] Univ Cambridge, Cambridge Res Inst, Canc Res UK, Li Ka Shing Ctr, Cambridge CB2 0RE, England. [Teschendorff, Andrew E.; Caldas, Carlos] Univ Cambridge, Dept Oncol, Li Ka Shing Ctr, Cambridge CB2 0RE, England. RP Azzato, EM (reprint author), Univ Cambridge, Dept Oncol, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England. EM ema32@cam.ac.uk RI Azzato, Elizabeth/A-1902-2009; Caldas, Carlos/A-7543-2008 FU Cancer Research UK [10118, ] NR 38 TC 20 Z9 21 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 3 AR R47 DI 10.1186/bcr2100 PG 10 WC Oncology SC Oncology GA 329LR UT WOS:000257869600015 PM 18507837 ER PT J AU Bennett, CN Green, JE AF Bennett, Christina N. Green, Jeffrey E. TI Unlocking the power of cross-species genomic analyses: identification of evolutionarily conserved breast cancer networks and validation of preclinical models SO BREAST CANCER RESEARCH LA English DT Review ID ESTROGEN-RECEPTOR-ALPHA; MAMMARY-TUMOR PROGRESSION; GENE-EXPRESSION PATTERNS; TRANSGENIC MICE; MOUSE MAMMARY; EXTRACELLULAR-MATRIX; DUCTAL MORPHOGENESIS; MOLECULAR PORTRAITS; INITIATING CELLS; MMTV-ERBB2 MICE AB The application of high-throughput genomic technologies has revealed that individual breast tumors display a variety of molecular features that require more personalized approaches to treatment. Several recent studies have demonstrated that a cross-species analytic approach provides a powerful means to filter through genetic complexity by identifying evolutionarily conserved genetic networks that are fundamental to the oncogenic process. Mouse-human tumor comparisons will provide insights into cellular origins of tumor subtypes, define interactive oncogenetic networks, identify potential novel therapeutic targets, and further validate as well as guide the selection of genetically engineered mouse models for preclinical testing. C1 [Bennett, Christina N.; Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, Bldg 37,Rm 4054,37 Convent Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov NR 85 TC 15 Z9 15 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 5 AR 213 DI 10.1186/bcr2125 PG 10 WC Oncology SC Oncology GA 381TO UT WOS:000261559000005 PM 18828875 ER PT J AU Booth, BW Boulanger, CA Smith, GH AF Booth, Brian W. Boulanger, Corinne A. Smith, Gilbert H. TI Selective segregation of DNA strands persists in long label retaining mammary cells during pregnancy SO BREAST CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; EPITHELIAL-CELLS; STEM-CELLS; OVARIAN HORMONES; PROGESTERONE-RECEPTOR; GLAND; MOUSE; CYCLE; BREAST; CANCER AB Introduction During pregnancy the mammary epithelial compartment undergoes extreme proliferation and differentiation, facilitated by stem/progenitor cells. Mouse mammary epithelium in nonpregnant mice contains long label-retaining epithelial cells (LREC) that divide asymmetrically and retain their template DNA strands. The role of LREC during alveogenesis has not been determined. Methods We performed immunohistochemistry and autoradiography on murine mammary glands that had been labeled with 5-bromodeoxyuridine (5BrdU) during allometric ductal growth to investigate the co-expression of DNA label retention and estrogen receptor-alpha or progesterone receptor during pregnancy. A second DNA label ([(3)H]-thymidine) was administered during pregnancy to identify label-retaining cells (LRC), which subsequently enter the cell cycle. Use of this methodology allowed us to investigate the co-localization of 5BrdU with smooth muscle actin, CD31, cytokeratin, and desmin in periductal or peri-acinar LRC in mammary tissue from pregnant mice subsequent to a long chase period in order to identify LRC. Results Estrogen receptor-alpha positive and progesterone receptor positive cells represented approximately 30% to 40% of the LREC, which is under 1.0% of the epithelial subpopulation. Pregnancy altered the percentage of LREC expressing estrogen receptor-alpha. LRC situated in periductal or peri-acinar positions throughout the gland do not express epithelial, endothelial, or myoepithelial markers, and these undefined LRCs persist throughout pregnancy. Additionally, new cycling LREC ([(3)H]-thymidine retaining) appear during alveologenesis, and LRC found in other tissue types (for example, endothelium and nerve) within the mammary fat pad become double labeled during pregnancy, which indicates that they may also divide asymmetrically. Conclusions Our findings support the premise that there is a subpopulation of LREC in the mouse mammary gland that persists during alveologenesis. These cells react to hormonal cues during pregnancy and enter the cell cycle while continuing to retain, selectively, their original template DNA. In addition, nonepithelial LRC are found in periductal or peri-acinar positions. These LRC also enter the cell cycle during pregnancy. During alveologenesis, newly created label-retaining ([(3)H]thymidine) epithelial cells appear within the expanding alveoli and continue to cycle and retain their original template DNA ([(3)H]-thymidine) strands, as determined by a second pulse of 5BrdU. C1 [Booth, Brian W.; Boulanger, Corinne A.; Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Convent Dr, Bethesda, MD 20892 USA. EM gs4d@nih.gov FU Center for Cancer Research; NCI; NIH FX We acknowledge the outstanding technical assistance of Gayle DeSalvo and SAIC, Frederick Cancer Research Center, in preparation of the animals, their tissues, the autoradiography, and the immunohistochemical staining. This work was supported entirely by the intramural research program of the Center for Cancer Research, NCI, NIH. NR 35 TC 22 Z9 23 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 5 AR R90 DI 10.1186/bcr2188 PG 11 WC Oncology SC Oncology GA 381TO UT WOS:000261559000027 PM 18950502 ER PT J AU Gierach, GL Lacey, JV Schatzkin, A Leitzmann, MF Richesson, D Hollenbeck, AR Brinton, LA AF Gierach, Gretchen L. Lacey, James V., Jr. Schatzkin, Arthur Leitzmann, Michael F. Richesson, Douglas Hollenbeck, Albert R. Brinton, Louise A. TI Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study SO BREAST CANCER RESEARCH LA English DT Article ID HORMONE-RECEPTOR STATUS; REGULAR ASPIRIN USE; LOW-DOSE ASPIRIN; LARGE COHORT; NSAID USE; WOMENS HEALTH; ASSOCIATION; POPULATION; ACETAMINOPHEN; PREVENTION AB Introduction By inhibiting cyclooxygenase-2, nonsteroidal anti-inflammatory drugs (NSAIDs) decrease aromatase activity and might reduce breast cancer risk by suppressing estrogen synthesis. Epidemiologic evidence for a protective role of NSAIDs in breast cancer, however, is equivocal. Methods We tested NSAID use for its association with breast cancer incidence in the National Institutes of Health-AARP Diet and Health Study, where 127,383 female AARP (formerly known as the American Association of Retired Persons) members with no history of cancer, aged 51 to 72 years, completed a mailed questionnaire (1996 to 1997). We estimated relative risks of breast cancer for NSAID exposures using multivariate Cox proportional hazards regression models. The state cancer registry and mortality index linkage identified 4,501 primary incident breast cancers through 31 December 2003, including 1,439 estrogen receptor (ER)-positive cancers and 280 ER-negative cancers. Results Proportional hazards models revealed no statistically significant association between overall NSAIDs and total breast cancer. As cyclooxygenase inhibition by aspirin (but not other NSAIDs) is irreversible, we tested associations by NSAID type. Although we observed no significant differences in risk for daily use (versus nonuse) of aspirin (relative risk = 0.93, 95% confidence interval = 0.85 to 1.01) or nonaspirin NSAIDS (relative risk = 0.96, 95% confidence interval = 0.87 to 1.05), risk of ER-positive breast cancer was significantly reduced with daily aspirin use (relative risk = 0.84, 95% confidence interval = 0.71 to 0.98) - a relationship not observed for nonaspirin NSAIDS. Neither aspirin nor nonaspirin NSAIDs were associated with risk of ER-negative breast cancer. Conclusion Breast cancer risk was not significantly associated with NSAID use, but daily aspirin use was associated with a modest reduction in ER-positive breast cancer. Our results provide support for further evaluating relationships by NSAID type and breast cancer subtype. C1 [Gierach, Gretchen L.; Lacey, James V., Jr.; Richesson, Douglas; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Res, Div Canc Epidemiol, NIH, Rockville, MD 20852 USA. [Gierach, Gretchen L.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Schatzkin, Arthur; Leitzmann, Michael F.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Hollenbeck, Albert R.] AARP, Org & Tracking Res Dept, Washington, DC 20049 USA. RP Gierach, GL (reprint author), NCI, Hormonal & Reprod Epidemiol Res, Div Canc Epidemiol, NIH, 6120 Execut Blvd,Suite 550, Rockville, MD 20852 USA. EM gierachg@mail.nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 FU Intramural NIH HHS NR 49 TC 51 Z9 54 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 2 AR R38 DI 10.1186/bcr2089 PG 13 WC Oncology SC Oncology GA 302BJ UT WOS:000255941100026 PM 18447943 ER PT J AU Leitzmann, MF Moore, SC Peters, TM Lacey, JV Schatzkin, A Schairer, C Brinton, LA Albanes, D AF Leitzmann, Michael F. Moore, Steven C. Peters, Tricia M. Lacey, James V., Jr. Schatzkin, Arthur Schairer, Catherine Brinton, Louise A. Albanes, Demetrius TI Prospective study of physical activity and risk of postmenopausal breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID HORMONE-RECEPTOR STATUS; RANDOMIZED CLINICAL-TRIAL; UNITED-STATES; RECREATIONAL EXERCISE; PROSPECTIVE COHORT; COLLEGE ALUMNI; BODY-SIZE; WOMEN; HEALTH; POPULATION AB Introduction To prospectively examine the relation of total, vigorous and non-vigorous physical activity to postmenopausal breast cancer risk. Methods We studied 32,269 women enrolled in the Breast Cancer Detection Demonstration Project Follow-up Study. Usual physical activity (including household, occupational and leisure activities) throughout the previous year was assessed at baseline using a self-administered questionnaire. Postmenopausal breast cancer cases were identified through self-reports, death certificates and linkage to state cancer registries. A Cox proportional hazards regression was used to estimate the relative risk and 95% confidence intervals of postmenopausal breast cancer associated with physical activity. Results During 269,792 person-years of follow-up from 1987 to 1998, 1506 new incident cases of postmenopausal breast cancer were ascertained. After adjusting for potential risk factors of breast cancer, a weak inverse association between total physical activity and postmenopausal breast cancer was suggested (relative risk comparing extreme quintiles = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.21). That relation was almost entirely contributed by vigorous activity (relative risk comparing extreme categories = 0.87; 95% confidence interval = 0.74 to 1.02; p for trend = 0.08). The inverse association with vigorous activity was limited to women who were lean (ie, body mass index <25.0 kg/m(2): relative risk = 0.68; 95% confidence interval = 0.54 to 0.85). In contrast, no association with vigorous activity was noted among women who were overweight or obese (ie, body mass index >= 25.0 kg/m(2): relative risk = 1.18; 95% confidence interval = 0.93 to 1.49; p for interaction = 0.008). Non-vigorous activity showed no relation to breast cancer (relative risk comparing extreme quintiles = 1.02; 95% confidence interval = 0.87 to 1.19; p for trend = 0.86). The physical activity and breast cancer relation was not specific to a certain hormone receptor subtype. Conclusions In this cohort of postmenopausal women, breast cancer risk reduction appeared to be limited to vigorous forms of activity; it was apparent among normal weight women but not overweight women, and the relation did not vary by hormone receptor status. Our findings suggest that physical activity acts through underlying biological mechanisms that are independent of body weight control. C1 [Leitzmann, Michael F.; Moore, Steven C.; Peters, Tricia M.; Schatzkin, Arthur; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Leitzmann, Michael F.] Univ Hosp Regensburg, Inst Epidemiol & Prevent Med, D-93053 Regensburg, Germany. [Lacey, James V., Jr.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Schairer, Catherine] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Leitzmann, MF (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,MSC 7232, Bethesda, MD 20892 USA. EM michael.leitzmann@klinik.uni-regensburg.de RI Albanes, Demetrius/B-9749-2015; Brinton, Louise/G-7486-2015; Moore, Steven/D-8760-2016 OI Brinton, Louise/0000-0003-3853-8562; Moore, Steven/0000-0002-8169-1661 FU NIGMS NIH HHS [T32 GM008444] NR 53 TC 36 Z9 36 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 5 AR R92 DI 10.1186/bcr2190 PG 11 WC Oncology SC Oncology GA 381TO UT WOS:000261559000029 PM 18976449 ER PT J AU Park, SK Kang, D McGlynn, KA Garcia-Closas, M Kim, Y Yoo, KY Brinton, LA AF Park, Sue Kyung Kang, Daehee McGlynn, Katherine A. Garcia-Closas, Montserrat Kim, Yeonju Yoo, Keun Young Brinton, Louise A. TI Intrauterine environments and breast cancer risk: meta-analysis and systematic review SO BREAST CANCER RESEARCH LA English DT Review ID UMBILICAL-CORD BLOOD; SERUM UNCONJUGATED ESTRIOL; IN-UTERO EXPOSURES; BIRTH-WEIGHT; PARENTAL AGE; UNITED-STATES; YOUNG-WOMEN; PERINATAL FACTORS; SUBSEQUENT RISK; SWEDISH WOMEN AB Introduction Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. Methods We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. Results We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 95% confidence interval [ CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [ 95% CI 1.01 to 1.31] for >= 4,000 g relative to < 3,000 g) and two birth weight categories (OR 1.09 [ 95% CI 1.02 to 1.18] for >= 3,000 g relative to < 3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. Conclusion Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood. C1 [Park, Sue Kyung; Kang, Daehee; Kim, Yeonju; Yoo, Keun Young] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. [Park, Sue Kyung; McGlynn, Katherine A.; Garcia-Closas, Montserrat; Brinton, Louise A.] NIH, Div Canc Epidemiol & Genet, NCI, Rockville, MD 20892 USA. [Park, Sue Kyung; Kang, Daehee] Seoul Natl Univ, Canc Res Inst, Seoul 110799, South Korea. [Yoo, Keun Young] Natl Canc Ctr, Goyang Si 410769, Gyeonggi Do, South Korea. RP Park, SK (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. EM suepark@snu.ac.kr RI Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Park, Sue Kyung/J-2757-2012; Kim, Yeonju/D-8948-2013; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562 FU Intramural NIH HHS NR 99 TC 69 Z9 72 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 1 AR R8 DI 10.1186/bcr1850 PG 34 WC Oncology SC Oncology GA 285YF UT WOS:000254811400015 PM 18205956 ER PT J AU Simeone, AM McMurtry, V Nieves-Alicea, R Saavedra, JE Keefer, LK Johnson, MM Tari, AM AF Simeone, Ann-Marie McMurtry, Vanity Nieves-Alicea, Rene Saavedra, Joseph E. Keefer, Larry K. Johnson, Marcella M. Tari, Ana M. TI TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells SO BREAST CANCER RESEARCH LA English DT Article ID S-TRANSFERASE-PI; IN-VITRO; MATRIX METALLOPROTEINASE-2; TISSUE INHIBITORS; GENE SUPPRESSES; PROTEIN-KINASE; TUMOR-GROWTH; METASTASIS; CYCLOOXYGENASE-2; EXPRESSION AB Introduction Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. High concentrations of nitric oxide (NO) suppress tumor invasion and metastasis in vivo. NO prodrugs generate large amounts of NO upon metabolism by appropriate intracellular enzymes, and therefore could have potential in the prevention and therapy of metastatic breast cancer. Methods The present study was designed to determine the effects of the NO-releasing prodrug O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JSK) on breast cancer invasion and the mechanisms involved. MDA-MB-231, MDA-MB-231/F10, and MCF-7/COX-2 were the three breast cancer cell lines tested. NO levels were determined spectrophotometrically using a NO assay kit. Invasion and the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs were determined using Matrigel invasion assays, an MMP array kit and ELISAs. The activity and expression of extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase mitogen-activated protein kinases were determined using western blot analyses. Results Under conditions by which JS-K was not cytotoxic, JS-K significantly decreased (P < 0.05) the invasiveness of breast cancer cells across the Matrigel basement membrane, which was directly correlated with NO production. JS-43-126, a non-NO-releasing analog of JS-K, had no effect on NO levels or invasion. JS-K increased (P < 0.05) TIMP-2 production, and blocking TIMP-2 activity with a neutralizing antibody significantly increased (P < 0.05) the invasive activity of JS-K-treated cells across Matrigel. JS-K decreased p38 activity, whereas the activity and the expression of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase were unaffected. Conclusion We report the novel findings that JS-K inhibits breast cancer invasion across the Matrigel basement membrane, and NO production is vital for this activity. Upregulation of TIMP-2 production is one mechanism by which JS-K mediates its anti-invasive effects. JS-K and other NO prodrugs may represent an innovative biological approach in the prevention and treatment of metastatic breast cancer. C1 [Simeone, Ann-Marie; McMurtry, Vanity; Nieves-Alicea, Rene; Tari, Ana M.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Saavedra, Joseph E.] NCI, SAIC Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Ft Detrick, MD 21702 USA. [Johnson, Marcella M.] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. RP Tari, AM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. EM atari@mdanderson.org RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural NIH HHS; NCI NIH HHS [CA 096300, N01-CO12400, N01CO12400, U54 CA096300]; PHS HHS [IDO1-014 U54] NR 45 TC 32 Z9 34 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 3 AR R44 DI 10.1186/bcr2095 PG 10 WC Oncology SC Oncology GA 329LR UT WOS:000257869600012 PM 18474097 ER PT J AU Smith, GH Medina, D AF Smith, Gilbert H. Medina, Daniel TI Re-evaluation of mammary stem cell biology based on in vivo transplantation SO BREAST CANCER RESEARCH LA English DT Review ID ESTROGEN-RECEPTOR-ALPHA; TEMPLATE DNA STRANDS; EPITHELIAL-CELLS; GLAND DEVELOPMENT; PRENEOPLASTIC PHENOTYPE; PROGESTERONE-RECEPTOR; LIFE SPAN; MOUSE; GROWTH; TISSUE AB Over nearly half a century, transplantation methods have been employed to regenerate the mammary gland in vivo. Recent highly cited reports claim to have demonstrated the regeneration of an entire functional mammary gland from a single mammary epithelial cell. Nevertheless, re- examination of the literature on the transplantation biology of mammary gland regeneration reveals that a complex, combinatorial interaction between variously differentiated mammary epithelial cells and the mammary fat pad stroma is indispensable to this process. In the present article, these issues are reviewed and discussed to provide a greater understanding of the complexity of these multiplex interactions. C1 [Smith, Gilbert H.] NIH, Mammary Stem Cell Biol Sect, Mammary Biol & Tumorigenesis Lab, CCR,NCI, Bethesda, MD 20892 USA. [Medina, Daniel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Smith, GH (reprint author), NIH, Mammary Stem Cell Biol Sect, Mammary Biol & Tumorigenesis Lab, CCR,NCI, 37 Convent Dr,Bldg 37,Rm 1106, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 37 TC 37 Z9 39 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 1 AR 203 DI 10.1186/bcr1856 PG 6 WC Oncology SC Oncology GA 285YF UT WOS:000254811400005 PM 18304381 ER PT J AU Smith, GH Medina, D AF Smith, Gilbert H. Medina, Daniel TI The future of mammary stem cell biology: the power of in vivo transplants - authors' response SO BREAST CANCER RESEARCH LA English DT Letter C1 [Smith, Gilbert H.] NCI, Mammary Stem Cell Biol Sect, Mammary Biol & Tumorigenesis Lab, CCR,NIH, Bethesda, MD 20892 USA. [Medina, Daniel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Smith, GH (reprint author), NCI, Mammary Stem Cell Biol Sect, Mammary Biol & Tumorigenesis Lab, CCR,NIH, Bethesda, MD 20892 USA. EM gs4d@nih.gov NR 3 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 3 AR 403 DI 10.1186/bcr1993 PG 1 WC Oncology SC Oncology GA 329LR UT WOS:000257869600006 ER PT J AU Woditschka, S Haag, JD Mau, B Lubet, RA Gould, MN AF Woditschka, Stephan Haag, Jill D. Mau, Bob Lubet, Ronald A. Gould, Michael N. TI Chemopreventive effects of celecoxib are limited to hormonally responsive mammary carcinomas in the neu-induced retroviral rat model SO BREAST CANCER RESEARCH LA English DT Article ID BREAST-CANCER; CYCLOOXYGENASE-2 INHIBITOR; EPITHELIAL-CELLS; IN-SITU; PREVENTION; EXPRESSION; TAMOXIFEN; AROMATASE; TUMORIGENESIS; INDUCTION AB Introduction While current breast cancer chemoprevention strategies using selective estrogen response modulators and aromatase inhibitors are quite successful, their effects are limited to hormonally responsive breast cancer. Hormonally nonresponsive breast cancer (including estrogen receptor-negative cancer) is associated with poor prognosis for patients, and few chemoprevention agents exist for this type of cancer. The cyclooxygenase-2 inhibitor celecoxib (Celebrex((R))) is a nonsteroidal anti-inflammatory drug and as such is a potential candidate for the prevention of hormonally nonresponsive breast cancer. Methods The chemopreventive effects of celecoxib were evaluated in the neu-induced retroviral rat mammary carcinogenesis model, to assess the efficacy of celecoxib on hormonally responsive and hormonally nonresponsive mammary carcinomas. Results Dietary celecoxib at 1,200 mg/kg diet was highly efficacious in the prevention of hormonally responsive mammary carcinomas in intact rats, decreasing tumor multiplicity by 56% (P < 0.0001) and by 74% (P = 0.0002) in two independent experiments. No significant effect was found, however, on hormonally nonresponsive mammary carcinomas of ovariectomized rats. Treatment with a combination diet, consisting of tamoxifen at 2 mg/kg diet and celecoxib at 1,200 mg/kg diet, reduced tumor multiplicity by 72% (P = 0.0002) in intact rats. This reduction was not statistically different from that observed with celecoxib alone. Furthermore, long-term treatment with celecoxib was not associated with reductions in tumor volume in either intact rats or ovariectomized rats. In contrast, tamoxifen treatment and the combination regimen caused significant reductions in tumor volumes in intact rats (P = 0.01 and P = 0.004, respectively). Consistent with these data, decreases in proliferation and increases in apoptosis were detected in tamoxifen-treated and combination diet-treated tumors. No such modulations were observed in celecoxibtreated tumors. Conclusion The chemopreventive effects of celecoxib appear to be limited to modulations in multiplicity of hormonally responsive mammary carcinomas. The fact that no synergistic or additive effects were observed in combination diet-treated rats raises the question of whether celecoxib is suitable for the prevention of hormonally nonresponsive breast cancer or for use in combination therapy with selective estrogen response modulators or aromatase inhibitors. C1 [Woditschka, Stephan; Haag, Jill D.; Gould, Michael N.] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. [Mau, Bob] Univ Wisconsin, Genom Ctr Wisconsin, Madison, WI 53706 USA. [Lubet, Ronald A.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Gould, MN (reprint author), Univ Wisconsin, McArdle Lab Canc Res, 1400 Univ Ave, Madison, WI 53706 USA. EM gould@oncology.wisc.edu RI Gould, Michael/C-7414-2014 FU NCI NIH HHS [R01 CA101201, CA101201] NR 28 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 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 1 AR R18 DI 10.1186/bcr1864 PG 9 WC Oncology SC Oncology GA 285YF UT WOS:000254811400025 PM 18279516 ER PT J AU Wright, MH Calcagno, AM Salcido, CD Carlson, MD Ambudkar, SV Varticovski, L AF Wright, Mollie H. Calcagno, Anna Maria Salcido, Crystal D. Carlson, Marisa D. Ambudkar, Suresh V. Varticovski, Lyuba TI Brca1 breast tumors contain distinct CD44(+)/CD24(-) and CD133(+) cells with cancer stem cell characteristics SO BREAST CANCER RESEARCH LA English DT Article ID DNA-DAMAGE RESPONSE; MAMMARY-GLAND CELLS; OVARIAN-CANCER; INHIBITOR 17-(DIMETHYLAMINOETHYLAMINO)-17-DEMETHOXYGELDANAMYCIN; SIGNALING PATHWAY; SPORADIC BREAST; MOUSE MODELS; IDENTIFICATION; MUTATIONS; GENE AB Introduction Whether cancer stem cells occur in BRCA1-associated breast cancer and contribute to therapeutic response is not known. Methods We generated and characterized 16 cell lines from five distinct Brca1deficient mouse mammary tumors with respect to their cancer stem cell characteristics. Results All cell lines derived from one tumor included increased numbers of CD44(+)/ CD24(-) cells, which were previously identified as human breast cancer stem cells. All cell lines derived from another mammary tumor exhibited low levels of CD44+/ CD24- cells, but they harbored 2% to 5.9% CD133(+) cells, which were previously associated with cancer stem cells in other human and murine tumors. When plated in the absence of attachment without presorting, only those cell lines that were enriched in either stem cell marker formed spheroids, which were further enriched in cells expressing the respective cancer stem cell marker. In contrast, cells sorted for CD44+/ CD24- or CD133+ markers lost their stem cell phenotype when cultured in monolayers. As few as 50 to 100 CD44+/ CD24- or CD133+ sorted cells rapidly formed tumors in nonobese diabetic/ severe combined immunodeficient mice, whereas 50- fold to 100- fold higher numbers of parental or stem cell depleted cells were required to form few, slow- growing tumors. Expression of stem cell associated genes, including Oct4, Notch1, Aldh1, Fgfr1, and Sox1, was increased in CD44+/ CD24- and CD133+ cells. In addition, cells sorted for cancer stem cell markers and spheroid- forming cells were significantly more resistant to DNA-damaging drugs than were parental or stem cell depleted populations, and they were sensitized to the drugs by the heat shock protein- 90 inhibitor 17- DMAG ( 17-dimethylaminoethylamino- 17- demethoxygeldanamycin hydrochloride). Conclusion Brca1- deficient mouse mammary tumors harbor heterogeneous cancer stem cell populations, and CD44+/ CD24- cells represent a population that correlates with human breast cancer stem cells. C1 [Wright, Mollie H.; Salcido, Crystal D.; Carlson, Marisa D.; Varticovski, Lyuba] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Calcagno, Anna Maria; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Varticovski, L (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM varticol@mail.nih.gov RI Ambudkar, Suresh/B-5964-2008; Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU Intramural NIH HHS NR 46 TC 314 Z9 348 U1 5 U2 35 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2008 VL 10 IS 1 AR R10 DI 10.1186/bcr1855 PG 16 WC Oncology SC Oncology GA 285YF UT WOS:000254811400017 PM 18241344 ER PT J AU Lissowska, J Gaudet, MM Brinton, LA Peplonska, B Sherman, M Szeszenia-Dabrowska, N Zatonski, W Garcia-Closas, M AF Lissowska, Jolanta Gaudet, Mia M. Brinton, Louise A. Peplonska, Beata Sherman, Mark Szeszenia-Dabrowska, Neonila Zatonski, Witold Garcia-Closas, Montserrat TI Intake of fruits, and vegetables in relation to breast cancer risk by hormone receptor status SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE fruit; vegetables; breast cancer risk; estrogen receptor; progesterone receptor ID DIET; CONSUMPTION AB The inconsistent associations between fruit and vegetable intake and breast cancer risk may be due to heterogeneity of associations by estrogen (ER) and progesterone receptor (PR) status of the tumors. We evaluated this hypothesis in a large (2,386 cases and 2,503 controls) population-based case-control study in Poland, conducted between 2000 and 2003. We observed significant associations between reduced overall risk of breast cancer and increasing levels of total fruit intake (odds ratio (OR) for highest versus lowest quartile = 0.76, 95%CI = 0.63-0.91; p-trend = 0.01), but not for total vegetable intake (1.13 (0.93-1.37), p-trend = 0.25), after controlling for age, energy intake and known risk factors for breast cancer. The inverse association with total fruit intake was stronger for risk of ER+ (0.69 (0.54-0.88), p-trend = 0.01) than ER- tumors (0.89 (0.67-1.19), p-trend = 0.57) (p-heterogeneity = 0.02). In conclusion, this study suggests that fruit intake might have differential associations for breast tumor subtypes defined by ER status. C1 Ctr Canc, Marie Curie Sklodowska Inst Oncol, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. NIH, NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Nofer Inst Occupant Med, Dept Environm & Occupat Epidemiol, Lodz, Poland. RP Lissowska, J (reprint author), Ctr Canc, Marie Curie Sklodowska Inst Oncol, Dept Canc Epidemiol & Prevent, WK Roentgena 5, PL-02781 Warsaw, Poland. EM lissowsj@coi.waw.pl RI Peplonska, Beata/F-6004-2010; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 NR 20 TC 16 Z9 16 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2008 VL 107 IS 1 BP 113 EP 117 DI 10.1007/s10549-007-9524-9 PG 5 WC Oncology SC Oncology GA 235LI UT WOS:000251235200013 PM 17318377 ER PT J AU Rosenberg, PS Alter, BP Link, DC Stein, S Rodger, E Bolyard, AA Aprikyan, AA Bonilla, MA Dror, Y Kannourakis, G Newburger, PE Boxer, LA Dale, DC AF Rosenberg, Philip S. Alter, Blanche P. Link, Daniel C. Stein, Steven Rodger, Elin Bolyard, Audrey A. Aprikyan, Andrew A. Bonilla, Mary A. Dror, Yigal Kannourakis, George Newburger, Peter E. Boxer, Laurence A. Dale, David C. TI Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE severe congenital neutropenia; neutrophil elastase ELA2; acute myeloid leukaemia; myelodysplastic syndromes; granulocyte colony-stimulating factor ID COLONY-STIMULATING FACTOR; FOLLOW-UP; THERAPY AB Severe congenital neutropenia (SCN) is a heterogeneous bone marrow failure syndrome predisposing to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We studied 82 North American and Australian SCN patients enrolled in the Severe Chronic Neutropenia International Registry who were on long-term treatment with granulocyte colony-stimulating factor and for whom the neutrophil elastase (ELA2) gene was sequenced. There was no significant difference in the risk of MDS/AML in patients with mutant versus wild-type ELA2: the respective cumulative incidences at 15 years were 36% and 25% (P = 0.96). Patients with either mutant or wild-type ELA2 should be followed closely for leukaemic transformation. C1 [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA. [Link, Daniel C.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Stein, Steven; Rodger, Elin; Bolyard, Audrey A.; Aprikyan, Andrew A.; Dale, David C.] Univ Washington, Dept Med, Seattle, WA USA. [Bonilla, Mary A.] St Josephs Childrens Hosp, Dept Pediat Hematol Oncol, Paterson, NJ USA. [Dror, Yigal] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Kannourakis, George] Univ Ballart, Ballart Canc Res Ctr, Wendouree, Vic, Australia. [Newburger, Peter E.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA. [Boxer, Laurence A.] Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 USA. RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd, Rockville, MD 20852 USA. EM rosenbep@mail.nih.gov OI Newburger, Peter/0000-0002-8615-673X FU Intramural NIH HHS [Z99 CA999999]; NIAID NIH HHS [1R24AI049392, K08 AI049392]; NIDDK NIH HHS [R01 DK054369, R01 DK054369-09, R01DK54369] NR 11 TC 49 Z9 50 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2008 VL 140 IS 2 BP 210 EP 213 DI 10.1111/j.1365-2141.2007.06897.x PG 4 WC Hematology SC Hematology GA 247AC UT WOS:000252048500010 PM 18028488 ER PT J AU Pacher, P Hasko, G AF Pacher, P. Hasko, G. TI Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE ischaemia-reperfusion; preconditioning; endocannabinoids; cannabinoid receptors; inflammation; leukocyte chemotaxis and adhesion ID ACID AMIDE HYDROLASE; FOCAL CEREBRAL-ISCHEMIA; RAT ISOLATED HEARTS; CB2 RECEPTOR; ENDOGENOUS CANNABINOIDS; MYOCARDIAL-ISCHEMIA; NITRIC-OXIDE; ENDOTHELIAL-CELLS; CIRRHOTIC CARDIOMYOPATHY; N-ACYLETHANOLAMINES AB Ischaemia-reperfusion (I/R) is a pivotal mechanism of organ injury during stroke, myocardial infarction, organ transplantation and vascular surgeries. Ischaemic preconditioning (IPC) is a potent endogenous form of tissue protection against I/R injury. On the one hand, endocannabinoids have been implicated in the protective effects of IPC through cannabinoid CB1/CB2 receptor-dependent and-independent mechanisms. However, there is evidence suggesting that endocannabinoids are overproduced during various forms of I/R, such as myocardial infarction or whole body I/R associated with circulatory shock, and may contribute to the cardiovascular depressive state associated with these pathologies. Previous studies using synthetic CB1 receptor agonists or knockout mice demonstrated CB1 receptor-dependent protection against cerebral I/R injury in various animal models. In contrast, several follow-up reports have shown protection afforded by CB1 receptor antagonists, but not agonists. Excitedly, emerging studies using potent CB2 receptor agonists and/or knockout mice have provided compelling evidence that CB2 receptor activation is protective against myocardial, cerebral and hepatic I/R injuries by decreasing the endothelial cell activation/inflammatory response (for example, expression of adhesion molecules, secretion of chemokines, and so on), and by attenuating the leukocyte chemotaxis, rolling, adhesion to endothelium, activation and transendothelial migration, and interrelated oxidative/nitrosative damage. This review is aimed to discuss the role of endocannabinoids and CB receptors in various forms of I/R injury (myocardial, cerebral, hepatic and circulatory shock) and preconditioning, and to delineate the evidence supporting the therapeutic utility of selective CB2 receptor agonists, which are devoid of psychoactive effects, as a promising new approach to limit I/R-induced tissue damage. C1 [Pacher, P.] NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Hasko, G.] UMDNJ New Jersey Med Sch, Dept Surg, Newark, NJ USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9143, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999] NR 128 TC 122 Z9 126 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2008 VL 153 IS 2 BP 252 EP 262 DI 10.1038/sj.bjp.0707582 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258QV UT WOS:000252883900009 PM 18026124 ER PT J AU Rajesh, M Mukhopadhyay, P Hasko, G Huffman, JW Mackie, K Pacher, P AF Rajesh, M. Mukhopadhyay, P. Hasko, G. Huffman, J. W. Mackie, K. Pacher, P. TI CB2 cannabinoid receptor agonists attenuate TNF-alpha-induced human vascular smooth muscle cell proliferation and migration SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE cannabinoids; cannabinoid 2 receptor; smooth muscle; proliferation; migration; antibodies ID TUMOR-NECROSIS-FACTOR; PHARMACOLOGICAL INHIBITION; ENDOTHELIAL-CELLS; NITRIC-OXIDE; IN-VIVO; ATHEROSCLEROSIS; ACTIVATION; ANGIOGENESIS; EXPRESSION; DISEASE AB Background and purpose: Vascular smooth muscle proliferation and migration triggered by inflammatory stimuli are involved in the development and progression of atherosclerosis and restenosis. Cannabinoids may modulate cell proliferation in various cell types through cannabinoid 2 (CB2) receptors. Here, we investigated the effects of CB2 receptor agonists on TNF-alpha-induced proliferation, migration and signal transduction in human coronary artery smooth muscle cells (HCASMCs). Experimental approach: HCASMCs were stimulated with TNF-alpha. Smooth muscle proliferation was determined by the extent of BrdU incorporation and the migration was assayed by modified Boyden chamber. CB2 and/or CB1 receptor expressions were determined by immunofluorescence staining, western blotting, RT-PCR, real-time PCR and flow cytometry. Key results: Low levels of CB2 and CB1 receptors were detectable in HCASMCs compared to the high levels of CB2 receptors expressed in THP-1 monocytes. TNF-alpha triggered up to similar to 80% increase (depending on the method used) in CB2 receptor mRNA and/or protein expression in HCASMCs, and induced Ras, p38 MAPK, ERK 1/2, SAPK/JNK and Akt activation, while increasing proliferation and migration. The CB2 agonists, JWH-133 and HU-308, dose-dependently attenuated these effects of TNF-alpha. Conclusions and implications: Since the above-mentioned TNF-alpha-induced phenotypic changes are critical in the initiation and progression of atherosclerosis and restenosis, our findings suggest that CB2 agonists may offer a novel approach in the treatment of these pathologies by decreasing vascular smooth muscle proliferation and migration. C1 [Rajesh, M.; Mukhopadhyay, P.; Pacher, P.] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Hasko, G.] UMDNJ New Jersey Med Sch, Dept Surg, Newark, NJ USA. [Huffman, J. W.] Clemson Univ, Howard L Hunter Chem Lab, Clemson, SC 29634 USA. [Mackie, K.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Mackie, Kenneth/B-7358-2011; Pacher, Pal/B-6378-2008; Mackie, Ken/E-3715-2013 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Mackie, Ken/0000-0001-8501-6199 FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999]; NIDA NIH HHS [DA03590, DA11322, R01 DA003590, R01 DA011322] NR 52 TC 85 Z9 90 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2008 VL 153 IS 2 BP 347 EP 357 DI 10.1038/sj.bjp.0707569 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258QV UT WOS:000252883900019 PM 17994109 ER PT J AU Le Foll, B Justinova, Z Tanda, G Goldberg, SR AF Le Foll, Bernard Justinova, Zuzana Tanda, Gianlugi Goldberg, Steven R. TI Future medications for tobacco and cannabis dependence SO BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE LA French DT Article DE tobacco; nicotine; cannabis; behavior, addictive/therapeutics ID DOPAMINE D-3 RECEPTOR; CONDITIONED PLACE PREFERENCES; NICOTINE-SEEKING BEHAVIOR; SQUIRREL-MONKEYS; DELTA(9)-TETRAHYDROCANNABINOL THC; DISCRIMINATIVE-STIMULUS; 2ND-ORDER SCHEDULES; WITHDRAWAL SYNDROME; DRUG-DEPENDENCE; COCAINE-SEEKING AB Worldwide more than 3 million deaths a year are attributable to smoking, and tobacco use is on the rise in developing countries. Consequently, smoking is one of the few causes of mortality that is increasing, with deaths projected to reach 10 million annually in 30-40 years. Cannabinoids, which are usually used in the form of marijuana, have become the most frequently used illicit drugs, but there is no pharmacological treatment for marijuana dependence. Although the dopaminergic system plays a critical role in reinforcing the effects of drugs of abuse, other neuro transmitter systems are also involved Here we review recent results obtained with antagonists targeting cannabinoid CBI receptors, dopamine D3 receptors and opioid receptors, that directly or indirectly modulate dopaminergic transmission. These promising approaches warrant clinical trials in the treatment of tobacco and marijuana dependence. C1 [Le Foll, Bernard] Univ Toronto, Ctr Addict & Mental Hlth, Translat Addict Res Lab, Toronto, ON, Canada. [Justinova, Zuzana; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. [Tanda, Gianlugi] Natl Inst Drug Abuse, Medicat Discovery Res Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. RP Le Foll, B (reprint author), 33 Russell St, Toronto, ON M5S 2S1, Canada. EM bernard_lefoll@camh.net RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011; Le Foll, Bernard/K-2952-2014 OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova, Zuzana/0000-0001-5793-7484; Le Foll, Bernard/0000-0002-6406-4973 FU Intramural NIH HHS [Z01 DA000003-22, Z99 DA999999] NR 52 TC 0 Z9 0 U1 0 U2 0 PU ACAD NATL MEDECINE PI PARIS 06 PA 16 RUE BONAPARTE, 75272 PARIS 06, FRANCE SN 0001-4079 J9 B ACAD NAT MED PARIS JI Bull. Acad. Natl. Med. PD JAN PY 2008 VL 192 IS 1 BP 45 EP 56 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 319SY UT WOS:000257185500008 PM 18663981 ER PT J AU Stern, JV Osinga, HM LeBeau, A Sherman, A AF Stern, Julie V. Osinga, Hinke M. LeBeau, Andrew Sherman, Arthur TI Resetting behavior in a model of bursting in secretory pituitary cells: Distinguishing plateaus from pseudo-plateaus SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article DE bursting; calcium oscillations; pituitary; stable and unstable manifolds; fast-slow systems ID PANCREATIC BETA-CELLS; VECTOR-FIELDS; CA2+ ENTRY; OSCILLATIONS; MANIFOLDS; CHANNELS AB We study a recently discovered class of models for plateau bursting, inspired by models for endocrine pituitary cells. In contrast to classical models for fold-homoclinic (square-wave) bursting, the spikes of the active phase are not supported by limit cycles of the frozen fast subsystem, but are transient oscillations generated by unstable limit cycles emanating from a subcritical Hopf bifurcation around a stable steady state. Experimental time courses are suggestive of such fold-subHopf models because the spikes tend to be small and variable in amplitude; we call this pseudo-plateau bursting. We show here that distinct properties of the response to attempted resets from the silent phase to the active phase provide a clearer, qualitative criterion for choosing between the two classes of models. The fold-homoclinic class is characterized by induced active phases that increase towards the duration of the unperturbed active phase as resets are delivered later in the silent phase. For the fold-subHopf class of pseudo-plateau bursting, resetting is difficult and succeeds only in limited windows of the silent phase but, paradoxically, can dramatically exceed the native active phase duration. C1 [Osinga, Hinke M.] Univ Bristol, Dept Engn Math, Bristol Ctr Appl Nonlinear Math, Bristol, Avon, England. [Stern, Julie V.; LeBeau, Andrew; Sherman, Arthur] NIDDK, Lab Biol Modeling, Natl Inst Hlth, Bethesda, MD USA. RP Osinga, HM (reprint author), Univ Bristol, Dept Engn Math, Bristol Ctr Appl Nonlinear Math, Queens Bldg,Univ Walk, Bristol, Avon, England. EM h.m.osinga@bristol.ac.uk OI Osinga, Hinke/0000-0003-2169-0883 FU Intramural NIH HHS NR 24 TC 20 Z9 20 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD JAN PY 2008 VL 70 IS 1 BP 68 EP 88 DI 10.1007/s11538-007-9241-x PG 21 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 248XR UT WOS:000252191000004 PM 17703340 ER PT J AU Bozec, A Bakiri, L Hoebertz, A Eferl, R Schilling, AF Konmenovic, V Scheuch, H Priemel, M Stewart, CL Amling, M Wagner, EF AF Bozec, A. Bakiri, L. Hoebertz, A. Eferl, R. Schilling, A. F. Konmenovic, V. Scheuch, H. Priemel, M. Stewart, C. L. Amling, M. Wagner, E. F. TI Osteoclast size and survival is controlled by FRA-2 through LIF/LIF-receptor signaling and hypoxia SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 [Bozec, A.; Bakiri, L.; Hoebertz, A.; Eferl, R.; Konmenovic, V.; Scheuch, H.; Wagner, E. F.] IMP, Res Inst Mol Pathol, Vienna, Austria. [Schilling, A. F.; Priemel, M.; Amling, M.] Dept Trauma, Hamburg, Germany. [Schilling, A. F.; Priemel, M.; Amling, M.] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Stewart, C. L.] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PY 2008 VL 82 SU 1 BP S126 EP S126 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306OS UT WOS:000256258300296 ER PT J AU Cohrs, CM Lisse, TS Hans, W Fuchs, H Przemeck, GKH de Angelis, MH AF Cohrs, C. M. Lisse, T. S. Hans, W. Fuchs, H. Przemeck, G. K. H. de Angelis, M. Hrabe TI Characterisation of a new mouse line displaying osteoarthritis, chondrodysplasia and ectopic bone SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 [Cohrs, C. M.; Hans, W.; Fuchs, H.; Przemeck, G. K. H.; de Angelis, M. Hrabe] German Res Ctr Environm Hlth GmbH, Helmholtz Ctr Munich, Inst Expt Genet, Neuherberg, Germany. [Lisse, T. S.] NICHHD, NIH, Bethesda, MD USA. RI lisse, thomas/C-8264-2009; Cohrs, Christian/L-7336-2013; Fuchs, Helmut/M-7347-2014 OI Fuchs, Helmut/0000-0002-5143-2677 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PY 2008 VL 82 SU 1 BP S138 EP S139 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306OS UT WOS:000256258300329 ER PT J AU Hans, W Lisse, TS Fuchs, H Abe, K Thiele, F Cohrs, CM Gailus-Durner, V de Angelis, MH AF Hans, W. Lisse, T. S. Fuchs, H. Abe, K. Thiele, F. Cohrs, C. M. Gailus-Durner, V. de Angelis, M. Hrabe TI New mouse models and mechanisms for bone and cartilage disorders SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 [Hans, W.; Fuchs, H.; Thiele, F.; Cohrs, C. M.; Gailus-Durner, V.; de Angelis, M. Hrabe] German Res Ctr Environm Hlth GmbH, Helmholtz Ctr Munich, Inst Expt Genet, Neuherberg, Germany. [Lisse, T. S.] NICHHD, NIH, Bone & Extracellular Matrix Branch, Bethesda, MD 20892 USA. [Abe, K.] Tokai Univ, Sch Med, Kanagawa 2591100, Japan. RI lisse, thomas/C-8264-2009; Cohrs, Christian/L-7336-2013; Gailus-Durner, Valerie/M-7337-2014; Fuchs, Helmut/M-7347-2014 OI Fuchs, Helmut/0000-0002-5143-2677 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PY 2008 VL 82 SU 1 BP S139 EP S140 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306OS UT WOS:000256258300332 ER PT J AU Marini, JC Obafemi, AA Abukhaled, MK Cintas, HL Troendle, JF Letocha, AD Reynolds, JC Paul, S AF Marini, J. C. Obafemi, A. A. Abukhaled, M. K. Cintas, H. L. Troendle, J. F. Letocha, A. D. Reynolds, J. C. Paul, S. TI Randomized dose comparison of pamidronate in children with types III and IV osteogenesis imperfecta: 3 vs 6 month cycles SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 [Marini, J. C.; Obafemi, A. A.; Abukhaled, M. K.; Letocha, A. D.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Troendle, J. F.] NICHD, Boimetry & Math Stat Branch, NIH, Bethesda, MD USA. [Cintas, H. L.; Reynolds, J. C.; Paul, S.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PY 2008 VL 82 SU 1 BP S142 EP S143 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306OS UT WOS:000256258300340 ER PT J AU Marini, JC Uveges, TE Collin-Osdoby, P Cabral, WA Ledgard, F Goldberg, L Bergwitz, C Forlino, A Osdoby, P Gronowicz, GA AF Marini, J. C. Uveges, T. E. Collin-Osdoby, P. Cabral, W. A. Ledgard, F. Goldberg, L. Bergwitz, C. Forlino, A. Osdoby, P. Gronowicz, G. A. TI Cellular mechanism of decreased bone formation in Brtl mouse: Increased osteoclasts are independent of decreased osteoblast function and RANKL/OPG ratio SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 [Marini, J. C.; Uveges, T. E.; Cabral, W. A.; Bergwitz, C.; Forlino, A.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA. [Collin-Osdoby, P.; Goldberg, L.; Osdoby, P.] Washington Univ, Div Bone & Mineral Metab, St Louis, MO USA. [Ledgard, F.; Gronowicz, G. A.] Univ Connecticut, Dept Orthopaed Surg, Farmington, CT USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PY 2008 VL 82 SU 1 BP S87 EP S87 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306OS UT WOS:000256258300191 ER PT J AU Smink, JJ Begay, V Schoenmaker, T Sterneck, E de Vries, TJ Leutz, A AF Smink, J. J. Begay, V. Schoenmaker, T. Sterneck, E. de Vries, T. J. Leutz, A. TI Transcription factor CCAAT/enhancer binding protein (C/EBP) beta isoform ratio regulates osteoclastogenesis and bone homeostasis SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 [Smink, J. J.; Begay, V.; Leutz, A.] Max Delbruck Ctr Mol Med, Berlin, Germany. [Schoenmaker, T.; de Vries, T. J.] Vrije Univ Amsterdam, Acad Ctr Dent Amsterdam, Amsterdam, Netherlands. [Schoenmaker, T.; de Vries, T. J.] Univ Amsterdam, Acad Ctr Dent Amsterdam, Amsterdam, Netherlands. [Sterneck, E.] Ctr Canc Res, Natl Canc Inst, Lab Cell & Dev Signaling, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PY 2008 VL 82 SU 1 BP S31 EP S32 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306OS UT WOS:000256258300054 ER PT J AU Umutyan, A Chiechi, C Beckett, LA Paterniti, DA Turrell, C Gandara, DR Davis, SW Wun, T Chen, MS Lara, PN AF Umutyan, Ari Chiechi, Christine Beckett, Laurel A. Paterniti, Debora A. Turrell, Corinne Gandara, David R. Davis, Sharon W. Wun, Ted Chen, Moon S., Jr. Lara, Primo N., Jr. TI Overcoming barriers to cancer clinical trial accrual - Impact of a mass media campaign SO CANCER LA English DT Article DE accrual rate; barriers to participation; cancer clinical trials; California Law SB37 ID BREAST-CANCER; ENROLLMENT; ATTITUDES; PARTICIPATION; ONCOLOGISTS; WILLINGNESS; PATTERNS; PREDICT; CARE AB BACKGROUND. Annually, only 3% of adult patients participate in cancer clinical trials (CCT). Accrual barriers include lack of CCT awareness and uncertain third-party coverage. In 2002, a California law (SB37) required all insurers to reimburse costs related to CCT. The objective of the current study was to increase awareness of CCT and SB37 through a mass multimedia campaign (MMC) in the University of California (UC) Davis (UCD) Cancer Center catchment area. The authors assessed willingness to participate in and accrual to CCT. METHODS. Changes in CCT/SB37 awareness and willingness to participate were investigated before the MMC versus after the MMC and in UCD respondents versus UC San Diego (UCSD) catchment respondents-a control group that was not exposed to the MMC-by Pearson chi-square and logistic regression analyses. RESULTS. Of 1081 post-MMC respondents, 957 were from UCD, and 124 from UCSD. UCD respondents had a greater awareness of CCT (59% vs 65%; P <.01) and SB37 (17% vs 32%; P <.01) compared with UCSD respondents. Willingness to participate did not change in either cohort. Awareness level predicted willingness (odds ratio, 2.3; P <.01). Blacks, Asians, and lowest income (<$25 K per year) groups were the least willing to participate (P <.01, P <.04, and P <.02, respectively). The CCT accrual rate at UCD was unchanged. CONCLUSIONS. CCT and SB37 awareness increased significantly in the UCD cohort after the MMC. However, it was unclear whether this increase was attributable entirely to the MMC or to varying demographic variables. Enhancing patient willingness and accrual will require targeting other variables, such as physician or resource barriers, rather than just CCT and reimbursement awareness. C1 [Umutyan, Ari; Chiechi, Christine; Beckett, Laurel A.; Paterniti, Debora A.; Turrell, Corinne; Gandara, David R.; Wun, Ted; Chen, Moon S., Jr.; Lara, Primo N., Jr.] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. [Paterniti, Debora A.] Ctr Hlth Serv Res Primary Care, Sacramento, CA USA. [Davis, Sharon W.] Natl Canc Inst, Canc Informat Serv, No Calif Canc Ctr, Fremont, CA USA. [Gandara, David R.; Wun, Ted; Lara, Primo N., Jr.] Vet Adm No Calif, Mather, CA USA. RP Lara, PN (reprint author), Univ Calif Davis, Ctr Canc, 4501 X St,Suite 3016, Sacramento, CA 95817 USA. EM primo.lara@ucdmc.ucdavis.edu OI Beckett, Laurel/0000-0002-2418-9843 FU NCI NIH HHS [R21 CA-03-501] NR 27 TC 22 Z9 22 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2008 VL 112 IS 1 BP 212 EP 219 DI 10.1002/cncr.23170 PG 8 WC Oncology SC Oncology GA 246GB UT WOS:000251994400027 PM 18008353 ER PT J AU Denduluri, N Yang, SX Berman, AW Nguyen, D Liewehr, DJ Steinberg, SM Swain, SM AF Denduluri, Neelima Yang, Sherry X. Berman, Arlene W. Nguyen, Diana Liewehr, David J. Steinberg, Seth M. Swain, Sandra M. TI Circulating biomarkers of bevacizumab activity in patients with breast cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE VEGF; sVEGFR-2; neoadjuvant; sVCAM-1; wound healing; VEGFR-2 ID ENDOTHELIAL GROWTH-FACTOR; CELL-ADHESION MOLECULE-1; PHASE-II TRIAL; E-SELECTIN; SURROGATE MARKER; SOLUBLE FORMS; FACTOR VEGF; ANGIOGENESIS; EXPRESSION; VCAM-1 AB Purpose: Noninvasive markers of anti-vascular endothelial growth factor (VEGF) therapy are needed. Soluble vascular cell adhesion molecule (sVCAM-1), soluble VEGF receptor-2 (sVEGFR-2), and plasma VEGF levels were assessed as potential biomarkers of therapy with bevacizumab. Tumor samples were evaluated for VEGFR-2 mutations before and after bevacizumab. Experimental design: Twenty-one patients with breast cancer underwent neoadjuvant treatment with bevacizumab for 1 cycle followed by 6 cycles of bevacizumab, chemotherapy, and filgrastim. Peripheral blood samples were collected at baseline, post cycles 1, 4 and 7. sVCAM-1, VEGF and sVEGFR-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). Exons 17-26 of VEGFR-2 were sequenced on tissue samples from 20 patients at baseline and post cycle 1 to evaluate for tumor mutations. Results: From baseline to post cycle 1, sVCAM-1 and sVEGFR-2 values increased by a median of 180.5 ng/ml (p < 0.0001) and 1927 ng/ml respectively (p = 0.0003). Baseline VEGF, sVEGFR-2, and sVCAM-1 levels nor changes in sVEGFR-2 and sVCAM-1 levels were associated with clinical response. Median baseline sVEGFR-2 levels were 11322 ng/ml and 7524 ng/ml in patients with (n = 5) and without (n = 6) wound healing problems respectively, (p = 0.052). In 40 samples where tumor VEGFR-2 sequencing was obtained, no mutations were seen compared to the reference sequence. Conclusions: sVCAM-1 and sVEGFR-2 values increased significantly after treatment with bevacizumab, possibly due to compensatory mechanisms secondary to VEGF inhibition. sVEGFR-2 levels were somewhat higher in patients with wound healing problems and may potentially predict patients at higher risk of this complication. There were no tumor VEGFR-2 mutations. C1 [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Denduluri, Neelima; Berman, Arlene W.] NCI, NIH, Ctr Canc Res, Med Oncol Branch,Breast Canc Sect, Bethesda, MD 20892 USA. [Yang, Sherry X.; Nguyen, Diana] NCI, NIH, Div Canc Treatment & Diag, Natl Clin Target Validat Lab, Bethesda, MD 20892 USA. [Liewehr, David J.; Steinberg, Seth M.] NCI, NIH, Ctr Canc Res, Off Clin Director,Biostat & Data Management Inst, Bethesda, MD 20892 USA. RP Swain, SM (reprint author), Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA. EM Sandra.M.Swain@medstar.net FU Intramural NIH HHS NR 41 TC 28 Z9 31 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2008 VL 7 IS 1 BP 15 EP 20 PG 6 WC Oncology SC Oncology GA 279OR UT WOS:000254365000003 PM 18059178 ER PT J AU Block, TM Marrero, J Gish, RG Sherman, M London, WT Srivastava, S Wagner, PD AF Block, Timothy M. Marrero, Jorge Gish, Robert G. Sherman, Morris London, W. Thomas Srivastava, Sudhir Wagner, Paul D. TI The degree of readiness of selected biomarkers for the early detection of hepatocellular carcinoma: Notes from a recent workshop SO CANCER BIOMARKERS LA English DT Article DE biomarkers; hepatocellular; carcinoma; fibrosis; cirrhosis ID HEPATITIS-B-VIRUS; CHRONIC LIVER-DISEASE; CHRONIC HBV INFECTION; ALPHA-FETOPROTEIN; C-VIRUS; GLYPICAN-3 EXPRESSION; VIRAL LOAD; SERUM; CARRIERS; PROTEIN AB This opinion piece evaluates the degree of readiness of 13 candidate biomarkers or panels of biomarkers for the early detection of hepatocellular carcinoma (HCC), or for the staging of liver fibrosis. As candidate biomarkers for the early detection of disease are identified, it is important to understand where they are in the developmental pipeline and how they might be employed. HCC is a growing public health problem, and its early detection is believed to be important in its management. Current detection methods are limited in usefulness or practicality, and there is a need for better methods to diagnose liver disease. Therefore, a number of candidate biomarkers, considered to be attractive because of their advanced stage of development or inherent scientific value, were evaluated for specificity and sensitivity for detection of liver disease. Study design, confirmatory evidence and assay practicality associated with each of the biomarkers are considered. The comments in this review reflect the authors' opinions and are based on a recent workshop convened by the Hepatitis B Foundation of America and the US National Cancer Institute's Early Detection Research Network. It is emphasized that only a selected set of biomarkers was considered; thus, this review is not comprehensive and not intended to review all candidate HCC biomarkers. C1 [Block, Timothy M.] Drexel Univ, Coll Med, Drexel Inst Biotechnol & Virol Res, Doylestown, PA USA. [Marrero, Jorge] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Gish, Robert G.] Calif Pacific Med Ctr, San Francisco, CA USA. [Sherman, Morris] Univ Toronto, Toronto, ON M5S 1A1, Canada. [London, W. Thomas] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Srivastava, Sudhir; Wagner, Paul D.] NCI, Bethesda, MD 20892 USA. RP Block, TM (reprint author), Drexel Inst, 3805 Old Easton Rd, Doylestown, PA 18902 USA. EM tmb46@drexel.edu NR 59 TC 28 Z9 30 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 1 BP 19 EP 33 PG 15 WC Oncology SC Oncology GA 303UV UT WOS:000256067300003 PM 18334731 ER PT J AU Macias, M Dean, M Atkinson, A Jimenez-Morales, S Garcia-Vazquez, FJ Saldana-Alvarez, Y Ramirez-Bello, J Chavez, M Orozco, L AF Macias, M. Dean, M. Atkinson, A. Jimenez-Morales, S. Garcia-Vazquez, F. J. Saldana-Alvarez, Y. Ramirez-Bello, J. Chavez, M. Orozco, L. TI Spectrum of RB1 gene mutations and loss of heterozygosity in Mexican patients with retinoblastoma: Identification of six novel mutations SO CANCER BIOMARKERS LA English DT Article DE retinoblastoma; RB1 gene; mutations; loss of heterozygosity; Mexican patients ID ISOLATED UNILATERAL RETINOBLASTOMA; SPORADIC RETINOBLASTOMA; GERMLINE MUTATIONS; HEREDITARY RETINOBLASTOMA; PENETRANCE RETINOBLASTOMA; SSCP ANALYSIS; MECHANISMS; EXPRESSION; CANCER; PCR AB RB1 mutation detection has greatly improved the clinical management of retinoblastoma and provides critical information to predict the risk of inheriting the disease. We screened for RB1 gene sequence alterations in both peripheral blood and tumor specimens from a total of 48 Mexican retinoblastoma patients using an SSCP-based screening approach followed by sequencing. Overall, 21 (43.8%) cases were bilateral and 27 (56.2%) were unilateral. Interestingly, 51.8% of unilateral patients developed the tumor before age 1 year and 10 of wich (71.4%) were diagnosed before the age of 6 months. Thirteen different oncogenic mutations were detected in 14/48 (29.2%) patients, 9 of which were germline (64.3%). Six of these mutations are novel (IVS3-1G > T, 125X, 389X, 610X, 750X and -149G > T). The most frequent types of mutation were frameshift and nonsense (30.8% each). Moreover, 5 intronic variants were identified, two of which are novel ( g. 41908 C/A and g.161976del6T). Loss of heterozygosity of the RB1 gene as assessed by intron1/BamHI and intron17/XbaI intragenic markers was 50.0% ( 18 of 36 informative cases), being higher in tumors with known mutations (76.9% vs 34.8%). This low mutation detection rate and the earlier age at diagnosis in unilateral retinoblastoma cases suggest that other RB1 inactivating mechanisms could be present in the retinoblastoma development. In this study, mutation analysis was not helpful to distinguish sporadic and hereditary retinoblastoma, so, other approaches are needed to improve the molecular diagnosis of retinoblastoma and supports further investigations of Mexican retinoblastoma patients. C1 [Macias, M.; Chavez, M.] Natl Inst Paediatr, Clin Res Lab, Mexico City, DF, Mexico. [Macias, M.] Univ Nacl Autonoma Mexico, PhD Prog Biomed Sci, Mexico City, DF, Mexico. [Dean, M.; Atkinson, A.] NCI, NIH, Frederick, MD 21701 USA. [Jimenez-Morales, S.; Saldana-Alvarez, Y.; Ramirez-Bello, J.; Orozco, L.] Natl Inst Genom Med, Lab Genom Complex Dis, Mexico City, DF, Mexico. [Garcia-Vazquez, F. J.] Natl Inst Pediat, Dept Pathol, Mexico City, DF, Mexico. RP Orozco, L (reprint author), Inst Nacl Med Genom, Periferico Sur 4124,Torre Zafiro II,6 Piso, Mexico City 01900, DF, Mexico. EM lorozco@inmegen.gob.mx OI Dean, Michael/0000-0003-2234-0631 NR 58 TC 5 Z9 5 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 2 BP 93 EP 99 PG 7 WC Oncology SC Oncology GA 303UW UT WOS:000256067400005 PM 18503160 ER PT J AU Patriotis, C Srivastava, S AF Patriotis, Christos Srivastava, Sudhir TI The National Cancer Institute Early Detection Research Network: 5th Scientific Workshop Biomarkers-at-a-Crossroads Foreword SO CANCER BIOMARKERS LA English DT Editorial Material C1 [Patriotis, Christos; Srivastava, Sudhir] NIH, Canc Biomarkers Res Grp, Rockville, MD 20852 USA. RP Patriotis, C (reprint author), NIH, Canc Biomarkers Res Grp, Execut Plaza N,Room 3144,6130 Execut Blvd, Rockville, MD 20852 USA. EM patriotisc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 121 EP 122 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300001 ER PT J AU Kramer, BS AF Kramer, Barnett S. TI Lessons learned in EDRN: The first eight years SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Kramer, Barnett S.] NIH, 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 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 124 EP 125 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300006 ER PT J AU Anton, K Crichton, DJ Thornquist, MD Grizzle, WE Brenner, DE Johnsey, D AF Anton, Kristin Crichton, Daniel J. Thornquist, Mark D. Grizzle, William E. Brenner, Dean E. Johnsey, Donald TI Colon biomarker atlas: An integrated resource for EDRN GI cancer biomarker information SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Anton, Kristin] Dartmouth Med Sch, Dartmouth, NS, Canada. [Crichton, Daniel J.] NASA, Jet Prop Lab, Washington, DC USA. [Grizzle, William E.] Univ Alabama, Birmingham, AL USA. [Thornquist, Mark D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Brenner, Dean E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Johnsey, Donald] Natl Canc Inst, Bethesda, MD 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 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 129 EP 130 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300014 ER PT J AU Sokoll, LJ Wang, Y Feng, Z Kagan, J Partin, AW Sanda, MG Thompson, IM Chan, DW AF Sokoll, Lori J. Wang, Yinghui Feng, Ziding Kagan, Jacob Partin, Alan W. Sanda, Martin G. Thompson, Ian M. Chan, Daniel W. TI [-2]proPSA improves prostate cancer detection: An EDRN validation study SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Sokoll, Lori J.; Partin, Alan W.; Chan, Daniel W.] Johns Hopkins Univ, Baltimore, MD USA. [Wang, Yinghui; Feng, Ziding] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kagan, Jacob] Natl Canc Inst, Bethesda, MD USA. [Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 NR 0 TC 1 Z9 1 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 135 EP 135 PG 1 WC Oncology SC Oncology GA 365JW UT WOS:000260403300024 ER PT J AU Dahlgren, J Warnick, G Stelling, D Johnsey, D Crichton, D Edelstein, C Hughes, S Kelly, S Lin, P Malnik, R Smerek, M Srivastava, S Reid, S Thornquist, M AF Dahlgren, Jackie Warnick, Greg Stelling, Deanna Johnsey, Don Crichton, Dan Edelstein, Cim Hughes, Steve Kelly, Sean Lin, Peter Malnik, Royce Smerek, Michelle Srivastava, Sudhir Reid, Suzanna Thornquist, Mark TI Early Detection Research Network (EDRN) eSIS project: Tracking study related research information and milestones using informatics tools SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Johnsey, Don; Srivastava, Sudhir] NCI, 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 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 137 EP 137 PG 1 WC Oncology SC Oncology GA 365JW UT WOS:000260403300027 ER PT J AU Erickson, HS Rodriguez-Canales, J Albert, PS Mukherjee, S Hu, N Goldstein, AM Chuaqui, RF Taylor, PR Emmert-Buck, MR AF Erickson, Heidi S. Rodriguez-Canales, Jaime Albert, Paul S. Mukherjee, Sumana Hu, Nan Goldstein, Alisa M. Chuaqui, Rodrigo F. Taylor, Philip R. Emmert-Buck, Michael R. TI Searching for 13q key players in esophageal squamous-cell carcinogenesis by qRT-PCR of microdissected tissues SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Erickson, Heidi S.; Rodriguez-Canales, Jaime; Mukherjee, Sumana; Chuaqui, Rodrigo F.; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Lab Pathol & Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Hu, Nan; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 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 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 139 EP 140 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300031 ER PT J AU Hughes, S Stelling, D Warnick, G Crichton, D Mattmann, C Reid, S Kelly, S Johnsey, D AF Hughes, Steve Stelling, Deanna Warnick, Greg Crichton, Dan Mattmann, Chris Reid, Suzanna Kelly, Sean Johnsey, Don TI An information model for biomarker research SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Johnsey, Don] NCI, 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 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 146 EP 147 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300044 ER PT J AU Shakooria, A Fukuoka, J Dracheva, T Shih, JH Shilo, K Nwosu, U Zhang, H Gill, R Jeon, H Clifford, R Franks, TJ Hewitt, S Travis, W Jen, J AF Shakooria, Abbas Fukuoka, Junya Dracheva, Tatiana Shih, Joanna H. Shilo, Konstantin Nwosu, Uchenna Zhang, Henry Gill, Rajbir Jeon, Hyosung Clifford, Robert Franks, Teri J. Hewitt, Stephen Travis, William Jen, Jin TI Identifying molecular markers in non-small cell lung cancer using computer-aided scoring and analysis (CASA) SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Shakooria, Abbas; Fukuoka, Junya; Dracheva, Tatiana; Nwosu, Uchenna; Gill, Rajbir; Jeon, Hyosung; Jen, Jin] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Shakooria, Abbas; Fukuoka, Junya; Dracheva, Tatiana; Zhang, Henry; Clifford, Robert] NCI, Lab Populat Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biometr Res Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Hewitt, Stephen] NCI, Tissue Array Res Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Shilo, Konstantin; Franks, Teri J.] Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. [Travis, William] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 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 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 147 EP 147 PG 1 WC Oncology SC Oncology GA 365JW UT WOS:000260403300045 ER PT J AU Hart, A Crichton, D Johnsey, D Mattmann, C Patriotis, C Kincaid, H Srivastava, S Thornquist, M AF Hart, Andrew Crichton, Dan Johnsey, Don Mattmann, Chris Patriotis, Christos Kincaid, Heather Srivastava, Sudhir Thornquist, Mark TI A web-based data management infrastructure for curation, annotation and dissemination of biomarker research results for the early detection of cancer SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Johnsey, Don; Patriotis, Christos; Srivastava, Sudhir] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 153 EP 154 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300058 ER PT J AU Meaburn, KJ Gudla, PR Nandy, K Lockett, SJ Misteli, T AF Meaburn, Karen J. Gudla, Prabhakar R. Nandy, Kaustav Lockett, Stephen J. Misteli, Tom TI Towards breast cancer diagnostics based on interphase spatial genome positioning SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Meaburn, Karen J.; Misteli, Tom] NCI, NIH, Cell Biol Genomes Grp, Bethesda, MD 20892 USA. [Gudla, Prabhakar R.; Nandy, Kaustav; Lockett, Stephen J.] NCI SAIC Frederick, Image Anal Lab, Frederick, MD 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 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 154 EP 155 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300060 ER PT J AU Ressom, HW Varghese, RS Goldman, L An, YM Loffredo, CA Abdel-Hamid, M Kyselova, Z Mechret, Y Novotny, M Drake, SK Goldman, R AF Ressom, Habtom W. Varghese, Rency S. Goldman, Lenka An, Yanming Loffredo, Christopher A. Abdel-Hamid, Mohamed Kyselova, Zuzana Mechret, Yehia Novotny, Milos Drake, Steven K. Goldman, Radoslav TI Computational methods for MALDI-TOF MS data analysis and their application for discovering peptide and glycan biomarkers of hepatocellular carcinoma SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Ressom, Habtom W.; Varghese, Rency S.; Goldman, Lenka; An, Yanming; Loffredo, Christopher A.; Goldman, Radoslav] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Abdel-Hamid, Mohamed] Univ Minho, Cairo, Egypt. [Abdel-Hamid, Mohamed] NHTMRI, Viral Hepatitis Res Lab, Cairo, Egypt. [Kyselova, Zuzana; Mechret, Yehia; Novotny, Milos] Natl Ctr Glycom & Glycoproteom, Dept Chem, Bloomington, IN USA. [Drake, Steven K.] NIH, Clin Chem Serv, Dept Lab Med, Bethesda, MD 20892 USA. RI Varghese, Rency/A-8770-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 158 EP 159 PG 2 WC Oncology SC Oncology GA 365JW UT WOS:000260403300065 ER PT J AU Schetter, AJ Leung, SY Sohn, JJ Zanetti, KA Bowman, ED Liu, CG Croce, CM Harris, CC AF Schetter, Aaron J. Leung, Suet Yi Sohn, Jane J. Zanetti, Krista A. Bowman, Elise D. Liu, Chang-gong Croce, Carlo M. Harris, Curtis C. TI MicroRNA expression in colon adenocarcinoma is associated with prognosis and therapeutic outcome SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Schetter, Aaron J.; Sohn, Jane J.; Zanetti, Krista A.; Bowman, Elise D.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, CCR, Bethesda, MD 20892 USA. [Leung, Suet Yi] Univ Hong Kong, Pokfulam, Peoples R China. [Liu, Chang-gong; Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 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 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 160 EP 160 PG 1 WC Oncology SC Oncology GA 365JW UT WOS:000260403300068 ER PT J AU Xiao, Y Gao, XG Gannot, G Emmert-Buck, MR Srivastava, S Wagner, PD Amos, MD Barker, PE AF Xiao, Yan Gao, Xiugong Gannot, Gallya Emmert-Buck, Michael R. Srivastava, Sudhir Wagner, Paul D. Amos, Michael D. Barker, Peter E. TI Quantitation of HER2 and telomerase biomarkers in solid tumors with IgY antibodies and nanocrystal detection SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 [Xiao, Yan] NIST, NCI, EDRN Canc Biomarker Reference Lab, Gaithersburg, MD 20899 USA. [Gao, Xiugong] Translabion, Clarksburg, MD USA. [Gannot, Gallya; Emmert-Buck, Michael R.] NCI, Pathogenesis Unit, Lab Pathol & Urol, Oncol Branch,Ctr Canc Res, Bethesda, MD 20892 USA. [Srivastava, Sudhir; Wagner, Paul D.] NCI, Canc Biomarker Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Amos, Michael D.; Barker, Peter E.] NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. EM yan.xiao@nist.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 168 EP 168 PG 1 WC Oncology SC Oncology GA 365JW UT WOS:000260403300083 ER PT J AU Marrero, JA Llovet, JM Nguyen, M Befeler, A Roberts, LR Reddy, RR Harnois, D Normolle, D Hui, Y Dalhgren, J Chia, D Lok, AS Wagner, PD Feng, ZD Schwartz, M AF Marrero, Jorge A. Llovet, Josep M. Nguyen, Mindie Befeler, Alex Roberts, Lewis R. Reddy, Rajender R. Harnois, Denise Normolle, Daniel Hui, Ying Dalhgren, Jackie Chia, David Lok, Anna S. Wagner, Paul D. Feng, Ziding Schwartz, Myron TI Phase 2 validation of AFP, DCP and AFP-L3 in early stage hepatocellular carcinoma SO CANCER BIOMARKERS LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Mt Sinai Univ, New York, NY USA. Stanford Univ, Palo Alto, CA 94304 USA. Mayo Clin, Rochester, MN USA. Univ Penn, Mayo Clin, Jacksonville, FL USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Bethesda, MD 20892 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2008 VL 4 IS 3 BP 183 EP 183 PG 1 WC Oncology SC Oncology GA 365JW UT WOS:000260403300110 ER PT J AU Kang, T Wei, Y Honaker, Y Yamaguchi, H Appella, E Hung, MC Piwnica-Worms, H AF Kang, Tiebang Wei, Yongkun Honaker, Yuchi Yamaguchi, Hiroshi Appella, Ettore Hung, Mien-Chie Piwnica-Worms, Helen TI GSK-3 beta targets Cdc25A for ubiquitin-mediated proteolysis, and GSK-3 beta inactivation correlates with Cdc25A overproduction in human cancers SO CANCER CELL LA English DT Article ID S-PHASE CHECKPOINT; CELL-CYCLE PROGRESSION; DNA-DAMAGE CHECKPOINT; HUMAN BREAST-CANCER; POLO-LIKE KINASES; BETA-TRCP; 7-HYDROXYSTAUROSPORINE UCN-01; PROTEIN-KINASE; I TRIAL; G(1)/S TRANSITION AB The Cdc25A phosphatase positively regulates cell-cycle transitions, is degraded by the proteosome throughout interphase and in response to stress, and is overproduced in human cancers. The kinases targeting Cdc25A for proteolysis during early cell-cycle phases have not been identified, and mechanistic insight into the cause of Cdc25A overproduction in human cancers is lacking. Here, we demonstrate that glycogen synthase kinase-3 beta (GSK-3 beta) phosphorylates Cdc25A to promote its proteolysis in early cell-cycle phases. Phosphorylation by GSK-3 beta requires priming of Cdc25A, and this can be catalyzed by polo-like kinase 3 (PIk-3). Importantly, a strong correlation between Cdc25A overproduction and GSK-3 beta inactivation was observed in human tumor tissues, indicating that GSK-3 beta inactivation may account for Cdc25A overproduction in a subset of human tumors. C1 [Kang, Tiebang; Piwnica-Worms, Helen] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Kang, Tiebang; Honaker, Yuchi; Piwnica-Worms, Helen] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Piwnica-Worms, Helen] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Wei, Yongkun; Hung, Mien-Chie] Univ Texas Houston, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. [Yamaguchi, Hiroshi; Appella, Ettore] NCI, Natl Inst Hlth, Cell Biol Lab, Bethesda, MD 20892 USA. RP Piwnica-Worms, H (reprint author), Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. EM hpiwnica@cellbiology.wustl.edu RI Piwnica-Worms, Helen/C-5214-2012 FU NIGMS NIH HHS [R01 GM047017, R01 GM047017-16, R01 GM047017-17] NR 63 TC 94 Z9 100 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2008 VL 13 IS 1 BP 36 EP 47 DI 10.1016/j.ccr.2007.12.002 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 250JH UT WOS:000252295400007 PM 18167338 ER PT J AU Lee, J Son, MJ Woolard, K Donin, NM Li, A Cheng, CH Kotliarova, S Kotliarov, Y Walling, J Ahn, S Kim, M Totonchy, M Cusack, T Ene, C Ma, H Su, Q Zenklusen, JC Zhang, W Maric, D Fine, HA AF Lee, Jeongwu Son, Myung Jin Woolard, Kevin Donin, Nicholas M. Li, Aiguo Cheng, Chui H. Kotliarova, Svetlana Kotliarov, Yuri Walling, Jennifer Ahn, Susie Kim, Misuk Totonchy, Mariam Cusack, Thomas Ene, Chibawanye Ma, Hilary Su, Qin Zenklusen, Jean Claude Zhang, Wei Maric, Dragan Fine, Howard A. TI Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells SO CANCER CELL LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; DNA METHYLATION; SELF-RENEWAL; CANCER; BRAIN; STAT3; MECHANISMS; POLYCOMB; TUMORS AB Despite similarities between tumor-initiating cells with stem-like properties (TICs) and normal neural stem cells, we hypothesized that there may be differences in their differentiation potentials. We now demonstrate that both bone morphogenetic protein (BMP)-mediated and ciliary neurotrophic factor (CNTF)-mediated Jak/STAT-dependent astroglial differentiation is impaired due to EZH2-dependent epigenetic silencing of BMP receptor 1B (BMPR1B) in a subset of glioblastoma TICs. Forced expression of BMPR1B either by transgene expression or demethylation of the promoter restores their differentiation capabilities and induces loss of their tumorigenicity. We propose that deregulation of the BMP developmental pathway in a subset of glioblastoma TICs contributes to their tumorigenicity both by desensitizing TICs to normal differentiation cues and by converting otherwise cytostatic signals to proproliferative signals. C1 [Lee, Jeongwu; Son, Myung Jin; Woolard, Kevin; Donin, Nicholas M.; Li, Aiguo; Cheng, Chui H.; Kotliarova, Svetlana; Kotliarov, Yuri; Walling, Jennifer; Ahn, Susie; Kim, Misuk; Totonchy, Mariam; Cusack, Thomas; Ene, Chibawanye; Ma, Hilary; Su, Qin; Zenklusen, Jean Claude; Zhang, Wei; Maric, Dragan; Fine, Howard A.] NCI, Neuro Oncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NCI, Neuro Oncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI leng, xianwei/F-9073-2011; Kotliarov, Yuri/B-6938-2017 FU Intramural NIH HHS [Z99 CA999999] NR 52 TC 243 Z9 252 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2008 VL 13 IS 1 BP 69 EP 80 DI 10.1016/j.ccr.2007.12.005 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 250JH UT WOS:000252295400010 PM 18167341 ER PT J AU Jia, L Coward, LC Kerstner-Wood, CD Cork, RL Gorman, GS Noker, PE Kitada, S Pellecchia, M Reed, JC AF Jia, Lee Coward, Lori C. Kerstner-Wood, Corenna D. Cork, Ronda L. Gorman, Gregory S. Noker, Patricia E. Kitada, Shinichi Pellecchia, Marrizio Reed, John C. TI Comparison of pharmacokinetic and metabolic profiling among gossypol, apogossypol and apogossypol hexaacetate SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE pharmacokinetics; metabolism; gossypol; apogossypol; apogossypol hexaacetate ID APOPTOSIS-BASED THERAPIES; CELL-LINES; IN-VITRO; (+/-)-GOSSYPOL; INHIBITION; RESOLUTION; PROTEINS; GROWTH; CANCER; PHASE AB Purpose To characterize the stability, pharmacokinetics and metabolism of analogs of gossypol, apogossypol and apogossypol hexaacetate to provide a basis for comparison. Methods Gossypol, apogossypol and apogossypol hexaacetate were incubated in plasma or liver microsomes from various species, or administered to mice, respectively, from which the stability, metabolism and pharmacokinetic profiles of these analogs were quantitatively determined using a liquid chromatography-mass spectrometry (LC/MS/MS) method. Results In various species of plasma, apogossypol and gossypol exhibited similar stability, while 20-40% of apogossypol hexaacetate was converted into apogossypol with concurrent formation of the corresponding di-, tri-, tetra-, and penta-acetates of apogossypol. (+/-)-Gossypol and (-)-gossypol showed comparable pharmacokinetic profile and oral bioavailability (12.2-17.6%) with some variations of clearance and V (ss) following oral and intravenous administration to mice. At the same molar dose, apogossypol showed delayed T (max)(1 h), a slower clearance rate and less distribution after administration to mice. Mono- and di-glucuronide conjugates of apogossypol were readily observed in mouse plasma following administration. Apogossypol formulated in sesame oil appeared to possess larger AUC and thus higher oral bioavailability than that formulated in cremophor EL:ethanol:saline. In contrast, intravenous apogossypol hexaacetate exhibited highest clearance rate partially due to its conversion into apogossypol. Concomitant with disappearance of apogossypol hexaacetate (iv), apogossypol converted from apogossypol hexaacetate was quantitatively detected, and accounted for similar to 30% of total plasma apogossypol hexaacetate. Oral apogossypol hexaacetate showed no bioavailability with little apogossypol occurring in the plasma. In human and mouse liver microsomes, glucuronide conjugates of apogossypol and its acetates were readily identified with the exception of gossypol glucuronidation. Apogossypol appeared more stable in human and mouse liver microsomal preparations than gossypol and apogossypol hexaacetate. Conclusions Apogossypol and gossypol show similar oral and intravenous pharmacokinetic profiles and in vitro stability although apogossypol appears to have a slower clearance rate, larger AUC, and better microsomal stability. Apogossypol hexaacetate converts to apogossypol in both in vitro and in vivo settings and lacks any quantifiable oral bioavailability. C1 NCI, Rockville, MD 20852 USA. So Res Inst, Birmingham, AL 35205 USA. Burnham Inst Med Res, La Jolla, CA 92037 USA. RP Jia, L (reprint author), NCI, Rm 8042,6130 Execut Blvd, Rockville, MD 20852 USA. EM jiale@mail.nih.gov FU NCI NIH HHS [N01-CM-07110, N01-CM-52203] NR 38 TC 16 Z9 18 U1 2 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2008 VL 61 IS 1 BP 63 EP 73 DI 10.1007/s00280-007-0446-3 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 216ZE UT WOS:000249916800008 PM 17356822 ER PT J AU Dawsey, SP Roth, MJ Adams, L Hu, N Wang, QH Taylor, PR Woodson, K AF Dawsey, Sonja P. Roth, Mark J. Adams, Lisa Hu, Nan Wang, Quan-Hong Taylor, Philip R. Woodson, Karen TI COX-2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia SO CANCER DETECTION AND PREVENTION LA English DT Article DE esophagus; neoplasms; cancer; cyclooxgenase-2; precancerous conditions; methylation; lymphocytes; squamous cell cancer ID PROSTATE-CANCER; CYCLOOXYGENASE-2; PYROSEQUENCING(TM); APOPTOSIS; CHINA AB Background: Previous studies have shown important effects of stromal elements in carcinogenesis. To explore the tumor-stromal relationship in esophageal neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically associated with the development of gastrointestinal cancers, in adjacent foci of epithelium, subepithelial lymphocytes and non-lymphocytic stromal cells found in sections of normal squamous epithelium, squamous dysplasia and invasive esophageal squamous cell carcinoma. Methods: Adjacent foci of epithelium, subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were laser microdissected from six fully embedded, ethanol fixed, esophagectomy samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter CpG site-specific hypermethylation status of COX-2 was determined using real-time methylation-specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation status of a subset of samples was confirmed by pyrosequencing. Results: Forty-nine microdissected foci were analyzed. COX-2 gene methylation was significantly more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17 (18%)) (Fisher's exact p = 0.05). Two of three epithelial samples and all three stromal samples that showed COX-2 methylation were adjacent to foci of methylated subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a subset of samples. Conclusions: In these esopohageal cancer patients, COX-2 gene methylation was more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in both grades of dysplasia and in foci of invasive cancer. These findings raise the possibility that methylation of subepithelial lymphocytes may be important for tumorigenesis. Future studies of gene methylation should consider separate evaluation of epithelial and non-epithelial cell populations. Published by Elsevier Ltd on behalf of International Society of Preventive Oncology. C1 [Roth, Mark J.] Natl Canc Inst, Nutr Epidemiol Branch, DCEG, Rockville, MD 20892 USA. [Dawsey, Sonja P.; Adams, Lisa; Woodson, Karen] NCI, Canc Genet Branch, Canc Res Ctr, Bethesda, MD 20892 USA. [Hu, Nan; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wang, Quan-Hong] Shanxi Canc Hosp & Inst, Dept Pathol, Taiyuan, Shanxi, Peoples R China. RP Roth, MJ (reprint author), Natl Canc Inst, Nutr Epidemiol Branch, DCEG, 6120 Execut Blvd,Suite 320,MSC 7232, Rockville, MD 20892 USA. EM mr166i@nih.gov OI Dawsey, Sonja/0000-0003-1605-3994 FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 5 Z9 7 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2008 VL 32 IS 2 BP 135 EP 139 DI 10.1016/j.cdp.2008.05.001 PG 5 WC Oncology SC Oncology GA 347HZ UT WOS:000259132500006 PM 18632220 ER PT J AU Chu, KC Hubbell, FA AF Chu, Kenneth C. Hubbell, F. Allan TI Reducing cancer health disparities: Perspective of the national cancer institute SO CANCER DETECTION AND PREVENTION LA English DT Article DE special populations network; pacific islanders; cancer prevention; cancer research; cancer training AB Background: The National Cancer Institute created the Special Population Network (SPN) to develop cancer awareness, research and training with partnerships from community and research organizations. Methods: Eighteen SPNs were funded with the goals of enlisting community partnerships, enhancing training opportunities for minority scientists, and conducting pilot research projects. Results: The SPN program concluded in 2005 after achieving many major milestones. Conclusion: This paper provides background information about the SPN and one of its programs, the Pacific Islander Cancer Control Network. (C) 2008 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 [Hubbell, F. Allan] UCI, Med Ctr, Dept Med, Chao Family Comprehens Canc Ctr, Orange, CA 92868 USA. [Hubbell, F. Allan] Univ Calif Irvine, Dept Med, Ctr Hlth Policy Res, Irvine, CA 92697 USA. [Chu, Kenneth C.] NCI, Ctr Reduce Canc Hlth Disparities, Rockville, MD 20852 USA. RP Hubbell, FA (reprint author), UCI, Med Ctr, Dept Med, Chao Family Comprehens Canc Ctr, 101 City Dr,Bldg 200, Orange, CA 92868 USA. EM fahubbel@uci.edu FU NCI NIH HHS [U01 CA086073-01, U01 CA086073, U01-CA086073] NR 4 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 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2008 VL 32 SU 1 BP S1 EP S3 DI 10.1016/j.cdp.2007.12.001 PG 3 WC Oncology SC Oncology GA 312FE UT WOS:000256653700001 PM 18343046 ER PT J AU Koutros, S Cross, AJ Sandler, DP Hoppin, JA Ma, XM Zheng, TZ Alavanja, MCR Sinha, R AF Koutros, Stella Cross, Amanda J. Sandler, Dale P. Hoppin, Jane A. Ma, Xiaomei Zheng, Tongzhang Alavanja, Michael C. R. Sinha, Rashmi TI Meat and meat mutagens and risk of prostate cancer in the agricultural health study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HETEROCYCLIC AMINE CONTENT; PHIP-DNA ADDUCTS; TURKISH POPULATION; PROSPECTIVE COHORT; CONJUGATION GENES; CYTOCHROMES P450; VARYING DEGREES; DIETARY-FAT; FOOD; POLYMORPHISMS AB Meats cooked at high temperatures, such as pan-frying or grilling, are a source of carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons. We prospectively examined the association between meat types, meat cooking methods, meat doneness, and meat mutagens and the risk for prostate cancer in the Agricultural Health Study. We estimated relative risks and 95% confidence intervals (95% CI) for prostate cancer using Cox proportional hazards regression using age as the underlying time metric and adjusting for state of residence, race, smoking status, and family history of prostate cancer. During 197,017 person-years of follow-up, we observed 668 incident prostate cancer cases (613 of these were diagnosed after the first year of follow-up and 140 were advanced cases) among 23,080 men with complete dietary data. We found no association between meat type or specific cooking method and prostate cancer risk. However, intake of well or very well done total meat was associated with a 1.26-fold increased risk of incident prostate cancer (95% CI, 1.02-1.54) and a 1.97-fold increased risk of advanced disease (95% CI, 1.26-3.08) when the highest tertile was compared with the lowest. Risks for the two heterocyclic amines 2-amino-3,4,8-trimethylimidazo-[4,5-f]qui-inoxaline and 2-amino-3,8-dimethylimidazo-[4,5b]quinoxaline were of borderline significance for incident disease [1.24 (95% CI, 0.96-1.59) and 1.20 (95% CI, 0.93-1.55), respectively] when the highest quintile was compared with the lowest. In conclusion, well and very well done meat was associated with an increased risk for prostate cancer in this cohort. C1 [Koutros, Stella; Alavanja, Michael C. R.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Cross, Amanda J.; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Koutros, Stella; Ma, Xiaomei; Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Sandler, Dale P.; Hoppin, Jane A.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8111, Rockville, MD 20852 USA. EM koutross@mail.nih.gov RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS [Z01 CP010119-12]; NCI NIH HHS [TU2 CA 105666, TU2 CA105666] NR 58 TC 48 Z9 50 U1 1 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2008 VL 17 IS 1 BP 80 EP 87 DI 10.1158/1055-9965.EPI-07-0392 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 253FK UT WOS:000252503900010 PM 18199713 ER PT J AU Troisi, R Lagiou, P Trichopoulos, D Xu, B Chie, L Stanczyk, FZ Potischman, N Adami, HO Hoover, RN Hsieh, CC AF Troisi, Rebecca Lagiou, Pagona Trichopoulos, Dimitrios Xu, Biao Chie, Lucy Stanczyk, Frank Z. Potischman, Nancy Adami, Hans-Olov Hoover, Robert N. Hsieh, Chung-Cheng TI Cord serum estrogens, androgens, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 in Chinese and US Caucasian neonates SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; ASIAN-AMERICAN WOMEN; HORMONE-LEVELS; PREGNANCY ESTRIOL; BIRTH-WEIGHT; UNCONJUGATED ESTRIOL; ALPHA-FETOPROTEIN; UNITED-STATES; PLASMA; TESTOSTERONE AB Markedly lower breast cancer incidence rates in Asians than Caucasians are not explained by established adult risk factors. Migration studies suggest the importance of early-life exposures, including perhaps the in utero period. Concentrations of steroid hormones and insulin-like growth factors (IGF) were measured in umbilical cord sera from pregnancies in Shanghai, China (n = 121) and Boston, MA (n = 111). Pregnancy characteristics were ascertained by interview and medical records. Means and percent differences in hormone concentrations comparing Chinese with Caucasians and 95% confidence intervals were estimated from linear regression models. Cord concentrations of androstenedione (91.9%), testosterone (257%), estriol (48.6%), and IGF binding protein-3 (21.1%) were significantly higher in the Chinese than U.S. samples, and cord prolactin was lower (-14.9%). Cord estradiol and IGF-I concentrations did not differ by race/ethnicity. With adjustment for gestational length, maternal age, pre-pregnancy weight, and weight gain, androstenedione (60.5%), testosterone (185%), and IGF binding protein-3 (40.4%) remained significantly higher in the Chinese, whereas the higher estriol and lower prolactin concentrations were attenuated. In addition, estradiol levels became lower in the Chinese (-29.8%) but did not reach statistical significance. Results were generally similar when restricted to first full-term pregnancies, with reduced estradiol concentrations in the Chinese reaching statistical significance after adjustment. These data are consistent with the hypothesis that elevated prenatal androgen exposure could mediate reductions in breast cancer risk. The meaning of the change in findings for estrogens after controlling for factors related to the pregnancy is unclear with regard to explaining international breast cancer differences. C1 [Troisi, Rebecca; Hoover, Robert N.] NCI, NIH, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Potischman, Nancy] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Troisi, Rebecca] Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH USA. [Lagiou, Pagona] Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. [Lagiou, Pagona; Trichopoulos, Dimitrios; Adami, Hans-Olov; Hsieh, Chung-Cheng] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chie, Lucy] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Lagiou, Pagona; Trichopoulos, Dimitrios; Adami, Hans-Olov; Hsieh, Chung-Cheng] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Xu, Biao] Fudan Univ, Sch Publ Hlth, Dept Epidemiol, Shanghai 200433, Peoples R China. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Reprod Endocrine Res Lab, Los Angeles, CA USA. [Hsieh, Chung-Cheng] Univ Massachusetts, Med Ctr, Dept Canc Biol, Worcester, MA USA. RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, Room 854,7297 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM troisir@mail.nih.gov NR 43 TC 12 Z9 12 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2008 VL 17 IS 1 BP 224 EP 231 DI 10.1158/1055-9965.EPI-07-0536 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 253FK UT WOS:000252503900029 PM 18199728 ER PT J AU Harris, TG Burk, RD Yu, H Minkoff, H Massad, LS Watts, DH Zhong, Y Gange, S Kaplan, RC Anastos, K Levine, AM Moxley, M Xue, XN Fazzari, M Palefsky, JM Strickler, HD AF Harris, Tiffany G. Burk, Robert D. Yu, Herbert Minkoff, Howard Massad, L. Stewart Watts, D. Heather Zhong, Ye Gange, Stephen Kaplan, Robert C. Anastos, Kathryn Levine, Alexandra M. Moxley, Michael Xue, Xiaonan Fazzari, Melissa Palefsky, Joel M. Strickler, Howard D. TI Insulin-like growth factor axis and oncogenic human papillomavirus natural history SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FACTOR-BINDING PROTEIN-3; FACTOR-I RECEPTOR; CERVICAL-CANCER; RISK; WOMEN; HIV; CARCINOGENICITY; PROLIFERATION; INFECTION; APOPTOSIS AB High serum levels of insulin-like growth factor-I (IGF-I) are reported to be a risk factor for several common cancers, and recent cross-sectional data suggest a possible additional association of IGF-I with cervical neoplasia. To prospectively assess whether circulating IGF-I levels influence the natural history of oncogenic human papillomavirus (HPV), the viral cause of cervical cancer, we conducted a pilot investigation of 137 women who underwent semiannual type-specific HPV DNA PCR testing and cervical cytology. Total IGF-I and IGF binding protein-3 (IGFBP-3), the most abundant IGFBP in circulation, were measured using baseline serum specimens. Having a high IGF-I/IGFBP-3 ratio was associated with increased persistence of oncogenic HPV infection [that is, a lower rate of clearance; adjusted hazard ratio (AHR), 0.14; 95% confidence interval (95% CI), 0.04-0.57], whereas IGFBP-3 was inversely associated with both the incident detection of oncogenic HPV (AHR, 0.35; 95% CI, 0.13-0.93) and the incidence of oncogenic HPV-positive cervical neoplasia (that is, squamous intra-epithelial lesions at risk of progression; AHR, 0.07; 95% CI, 0.01-0.66). These prospective data provide initial evidence that the IGF axis may influence the natural history of oncogenic HPV. C1 [Harris, Tiffany G.; Burk, Robert D.; Zhong, Ye; Kaplan, Robert C.; Anastos, Kathryn; Xue, Xiaonan; Fazzari, Melissa; Strickler, Howard D.] Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Yu, Herbert] Yale Univ, New Haven, CT USA. [Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA. [Minkoff, Howard] SUNY Downstate, Brooklyn, NY 11219 USA. [Massad, L. Stewart] So Illinois Univ, Sch Med, Springfield, IL USA. [Watts, D. Heather] NICHHD, NIH, Bethesda, MD 20892 USA. [Gange, Stephen] Johns Hopkins Univ, Baltimore, MD USA. [Levine, Alexandra M.] Univ So Calif, Los Angeles, CA USA. [Moxley, Michael] Univ Virginia, Charlottesville, VA USA. [Palefsky, Joel M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Strickler, HD (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer 1308, Bronx, NY 10461 USA. EM strickle@aecom.yu.edu RI Kaplan, Robert/A-2526-2011; OI Gange, Stephen/0000-0001-7842-512X FU NCI NIH HHS [R01 CA 085178]; NCRR NIH HHS [M01 RR 00071, M01 RR 00079, M01 RR 00083]; NIAID NIH HHS [U01 AI 34994, U01 AI 31834, U01 AI 34989, U01 AI 34993, U01 AI 35004, U01 AI 42590]; NICHD NIH HHS [U01 HD 32632] NR 28 TC 16 Z9 16 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2008 VL 17 IS 1 BP 245 EP 248 DI 10.1158/1055-9965.EPI-07-0686 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 253FK UT WOS:000252503900032 PM 18199731 ER PT J AU Ochiai, H Archer, GE Herndon, JE Kuan, CT Mitchell, DA Bigner, DD Pastan, IH Sampson, JH AF Ochiai, Hidenobu Archer, Gary E. Herndon, James E., II Kuan, Chien-Tsun Mitchell, Duane A. Bigner, Darell D. Pastan, Ira H. Sampson, John H. TI EGFRvIII-targeted immunotoxin induces antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE astrocytoma; epidermal growth factor receptor; immunotherapy; immunotoxins; T lymphocytes ID RECURRENT MALIGNANT GLIOMA; CENTRAL-NERVOUS-SYSTEM; DENDRITIC CELLS; RECOMBINANT IMMUNOTOXINS; BRAIN-TUMORS; IN-VIVO; GROWTH; SELF; OSTEOSARCOMA; XENOGRAFTS AB Purpose Immunotoxins as anti-cancer therapeutics have several potential advantages over conventional agents including a high specificity, extraordinary potency, and a lack of an identified mechanism for resistance. It has been clearly demonstrated that Pseudomonas-based immunotoxins have a direct cytotoxic effect. However, delayed and often dramatic antitumor responses seen in human studies with targeted toxins led us to hypothesize that immunologic responses may be a secondary mechanism that enhances the therapeutic efficacy of these novel drugs. Experimental design This hypothesis was tested in a murine system using an immunotoxin, MR1-1 [MR1-1(dsFv)-PE38KDEL], that targets a syngeneic murine homologue of the tumor-specific human epidermal growth factor mutation, EGFRvIII, expressed on a murine cell line. Results Intratumoral treatment with MR1-1 eliminated EGFRvIII-expressing tumors (P < 0.0001). The antitumor activity of MR1-1 was dependent on the expression of EGFRvIII on some, but not all tumors cells, and was significantly inhibited in the absence of CD4+ (P = 0.0193) and CD8+ (P = 0.0193) T cells. MR1-1 induced EGFRvIII-specific immunity (P < 0.0005) and produced long lasting immunity against tumors expressing EGFRvIII as well as EGFRvIII-negative tumors. Conclusions These data suggest that immunotoxins may not be strictly dependent on direct cytotoxicity for their efficacy, but may also be potent inducers of antitumor immunity active even against cells that do not express the targeted antigen. C1 Duke Univ, Med Ctr, Dept Surg Neurosurg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Dept Surg Neurosurg, Box 3050, Durham, NC 27710 USA. EM john.sampson@duke.edu FU Intramural NIH HHS; NCI NIH HHS [1R01 CA097222, R01 CA097611-05, R01 CA097611, R01 CA097611-03, R01 CA097611-02, R01 CA097611-04, 1R01 CA097611, P50 CA108786-010003, R01 CA097222-01, P50 CA108786, R01 CA097222, 1P50 CA108786-01, R01 CA097611-01, R01 CA097222-02]; NCRR NIH HHS [K23 RR016065, K23 RR016065-04, K23 RR16065, K23 RR016065-02, K23 RR016065-03, K23 RR016065-05]; NINDS NIH HHS [2P50-NS20023-21, P50 NS020023] NR 28 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2008 VL 57 IS 1 BP 115 EP 121 DI 10.1007/s00262-007-0363-7 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA 225SO UT WOS:000250538000011 PM 17634939 ER PT J AU Thiebaut, ACM Kipnis, V Schatzkin, A Freedman, LS AF Thiebaut, Anne C. M. Kipnis, Victor Schatzkin, Arthur Freedman, Laurence S. TI The role of dietary measurement error in investigating the hypothesized link between dietary fat intake and breast cancer - A story with twists and turns SO CANCER INVESTIGATION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; ENERGY-ADJUSTMENT MODELS; NUTRITIONAL EPIDEMIOLOGY; POOLED ANALYSIS; AMERICAN WOMEN; MAMMARY-TUMORS; FOLLOW-UP; RISK; HEALTH; COHORT AB The association between dietary fat and breast cancer is one of the most controversial hypotheses in nutritional epidemiology. In this editorial, the authors review the evidence from animal and human studies, including international correlation, case-control, cohort studies, intervention trials, and studies comparing dietary assessment instruments. The authors emphasize the importance of the role played by measurement error arising from assessing dietary habits using self-reported questionnaires, as it can distort estimated associations, not necessarily towards the absence of an association. They describe the twists and turns of the dietary fat and breast cancer debate that have revolved around this issue. C1 [Thiebaut, Anne C. M.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kipnis, Victor] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. [Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, Tel Hashomer, Israel. RP Thiebaut, ACM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 3033, Bethesda, MD 20892 USA. EM ann.thiebaut@yahoo.com NR 50 TC 20 Z9 21 U1 3 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2008 VL 26 IS 1 BP 68 EP 73 DI 10.1080/07357900701527918 PG 6 WC Oncology SC Oncology GA 250QN UT WOS:000252315200011 PM 18181048 ER PT J AU Stewart, TJ Lutsiak, MEC Abrams, SI AF Stewart, Trina J. Lutsiak, M. E. Christine Abrams, Scott I. TI Immune consequences of protracted host-tumor interactions in a transgenic mouse model of mammary carcinoma SO CANCER INVESTIGATION LA English DT Article DE mammary carcinoma tumor model; immunobiology; host-tumor interactions; inflammatory mediators; immune suppression; MMTV-PyMT; transgenic ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; BREAST-CANCER PATIENTS; REGULATORY T-CELLS; MYELOID SUPPRESSOR-CELLS; NECROSIS-FACTOR-ALPHA; PERIPHERAL-BLOOD; OVARIAN-CANCER; METASTATIC-DISEASE; DENDRITIC CELLS; SERUM-LEVELS AB A transgenic mouse model of autochthonous mammary carcinoma was chosen to study the impact of tumor progression on the immune system over an extended period. We found: i) that splenocyte numbers, particularly myeloid cells, increased concurrently with tumor burden; ii) the percentage of tumor-infiltrating Treg cells was similar to that in human breast cancer; iii) suppressed T cell proliferation and cytokine production and; iv) significantly elevated MCP-1 and TNF-alpha in the sera of tumor-bearing mice. The modified immune status in these tumor-bearing hosts is consistent with a "syndrome" that likely impacts the efficacy of cancer immunosurveillance and response to therapy. C1 [Stewart, Trina J.; Lutsiak, M. E. Christine; Abrams, Scott I.] NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr Bldg 10-5B46, Bethesda, MD 20892 USA. EM sa47z@nih.gov RI Stewart, Trina/F-5967-2012 OI Stewart, Trina/0000-0003-3220-9231 FU Intramural NIH HHS NR 73 TC 7 Z9 7 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2008 VL 26 IS 3 BP 237 EP 249 DI 10.1080/07357900701708419 PG 13 WC Oncology SC Oncology GA 270OE UT WOS:000253729300004 PM 18317964 ER PT J AU Simon, R AF Simon, Richard TI Challenges of microarray data and the evaluation of gene expression profile signatures SO CANCER INVESTIGATION LA English DT Article ID CLINICAL-TRIAL DESIGN; BREAST-CANCER; PREDICTION; CLASSIFICATION; CHEMOTHERAPY; VALIDATION; ONCOLOGY; CLASSIFIERS; DISCOVERY; PATTERNS C1 NCI, Biometr Res Lab, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Lab, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 37 TC 9 Z9 9 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2008 VL 26 IS 4 BP 327 EP 332 DI 10.1080/07357900801971032 PG 6 WC Oncology SC Oncology GA 293XZ UT WOS:000255370000001 PM 18443951 ER PT J AU Halpern, MT Yabroff, KR AF Halpern, Michael T. Yabroff, K. Robin TI Prevalence of outpatient cancer treatment in the United States: Estimates from the Medical Panel Expenditures Survey (MEPS) SO CANCER INVESTIGATION LA English DT Article DE outpatient; treatment; MEPS ID ADJUVANT CHEMOTHERAPY; COLON-CANCER AB Little is known regarding the prevalence of outpatient cancer treatment in the U.S. We analyzed nationally-representative data from the 2000-2004 Medical Expenditure Panel Survey to estimate the number of U.S. cancer patients receiving outpatient chemotherapy and/or radiation therapy annually. Each year, over 1.1 million individuals are estimated to receive chemotherapy or radiation therapy for cancer. Cancer patients younger than 65 receiving treatment who were uninsured were less likely to receive chemotherapy or combined chemotherapy/radiation therapy than were those with public or private insurance. These estimates may be useful for understanding the burden of cancer care and development of programs for cancer survivors. C1 [Halpern, Michael T.] Amer Canc Soc, Hlth Services Res, Atlanta, GA 30303 USA. [Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. RP Halpern, MT (reprint author), Amer Canc Soc, Hlth Services Res, 250 Williams St, Atlanta, GA 30303 USA. EM michael.halpern@cancer.org OI Yabroff, K. Robin/0000-0003-0644-5572 NR 17 TC 11 Z9 11 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2008 VL 26 IS 6 BP 647 EP 651 DI 10.1080/07357900801905519 PG 5 WC Oncology SC Oncology GA 319CO UT WOS:000257141900015 PM 18584358 ER PT J AU Aragon-Ching, JB Dahut, WL AF Aragon-Ching, Jeanny B. Dahut, William L. TI The role of angiogenesis inhibitors in prostate cancer SO CANCER JOURNAL LA English DT Article DE angiogenesis; prostate cancer; drugs; bevacizumab; thalidomide ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; TUMOR ANGIOGENESIS; SOLID TUMORS; TYROSINE KINASE; FACTOR RECEPTOR; ANTITUMOR-ACTIVITY; BREAST-CARCINOMA; PLUS THALIDOMIDE; DOCETAXEL AB Prostate cancer is the leading noncutaneous malignancy in American men. Only the combination of docetaxel and prednisone has been shown to improve survival in patients with metastatic castrate-resistant Prostate cancer. However, responses are short and a search for better agents either alone or synergistic with chemotherapy continues to be an urgent medical need. Angiogenesis has been shown to be a prerequisite event for tumor growth and metastasis in prostate cancer. Several strategies have been used to target angiogenesis in prostate cancer. These include blocking of pro-angiogenic factors via monoclonal antibodies or small molecule inhibitors targeting downstream signaling effector pathways, direct inhibition of endothelial cells, or targeting other receptors involved in cell adhesion, proliferation, and survival. Agents such as thalidomide and bevacizumab have shown encouraging results in phase II trials, and this review focuses on the clinical trials that have used these agents and other novel agents. The use of angiogenesis inhibitors is rapidly emerging as a promising treatment strategy in a variety of solid tumors, currently including prostate cancer. C1 [Dahut, William L.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Aragon-Ching, Jeanny B.] NIH, NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Dahut, WL (reprint author), NCI, Med Oncol Branch, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov OI Aragon-Ching, Jeanny/0000-0002-6714-141X FU Intramural NIH HHS NR 68 TC 25 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2008 VL 14 IS 1 BP 20 EP 25 DI 10.1097/PPO.0b013e318161c014 PG 6 WC Oncology SC Oncology GA 259OG UT WOS:000252948000006 PM 18303479 ER PT J AU Arlander, SJH Greene, BT Innes, CL Paules, RS AF Arlander, Sonnet J. H. Greene, Bryan T. Innes, Cynthia L. Paules, Richard S. TI DNA protein kinase-dependent G(2) checkpoint revealed following knockdown of ataxia-telangiectasia mutated in human mammary epithelial cells SO CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; IONIZING-RADIATION; REPAIR INHIBITION; DAMAGE CHECKPOINT; REQUIRES ATM; CANCER; CYCLE; PHOSPHORYLATION; EXPRESSION; TARGET AB Members of the phosphatidylinositol 3-kinase-related kinase family, in particular the ataxia-telangiectasia mutated (ATM) kinase and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), regulate cellular responses to DNA double-strand breaks. Increased sensitivity to ionizing radiation (IR) in DNA-PKcs- or ATM-deficient cells emphasizes their important roles in maintaining genome stability. Furthermore, combined knockout of both kinases is synthetically lethal, suggesting functional complementarity. In the current study, using human mammary epithelial cells with ATM levels stably knocked down by > 90%, we observed an IR-induced G(2) checkpoint that was only slightly attenuated. In marked contrast, this G(2) checkpoint was significantly attenuated with either DNA-PK inhibitor treatment or RNA interference knockdown of DNA-PKcs, the catalytic subunit of DNA-PK, indicating that DNA-PK contributes to the G(2) checkpoint in these cells. Furthermore, in agreement with the checkpoint attenuation, DNA-PK inhibition in ATM-knockdown cells resulted in reduced signaling of the checkpoint kinase CHK1 as evidenced by reduced CHK1 phosphorylation. Taken together, these results show a DNA-PK-dependent component to the IR-induced G(2) checkpoint, in addition to the well-defined ATM-dependent component. This may have important implications for chemotherapeutic strategies for breast cancers. C1 [Arlander, Sonnet J. H.; Greene, Bryan T.; Innes, Cynthia L.; Paules, Richard S.] NIEHS, Environm Stress & Canc Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Paules, RS (reprint author), NIEHS, Environm Stress & Canc Grp, NIH, POB 12233,Mail Drop D2-03, Res Triangle Pk, NC 27709 USA. EM paules@niehs.nih.gov FU Intramural NIH HHS [Z01 ES021157-17] NR 50 TC 19 Z9 25 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2008 VL 68 IS 1 BP 89 EP 97 DI 10.1158/0008-5472.CAN-07-0675 PG 9 WC Oncology SC Oncology GA 247IP UT WOS:000252072100015 PM 18172300 ER PT J AU Sabatino, M Zhao, Y Voiculescu, S Monaco, A Robbins, P Karai, L Nickoloff, BJ Maio, M Selleri, S Marincola, FM Wang, E AF Sabatino, Marianna Zhao, Yingdong Voiculescu, Sonia Monaco, Alessandro Robbins, Paul Karai, Laszlo Nickoloff, Brian J. Maio, Michele Selleri, Silvia Marincola, Francesco M. Wang, Ena TI Conservation of genetic alterations in recurrent melanoma supports the melanoma stem cell hypothesis SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; MESSENGER-RNA AMPLIFICATION; CYTOGENETIC CHARACTERIZATION; CHROMOSOMAL IMBALANCES; METASTATIC MELANOMAS; MICROARRAY ANALYSIS; MALIGNANT-MELANOMA; BREAST-CANCER; EXPRESSION; LINES AB It is generally accepted that human cancers derive from a mutated single cell. However, the genetic steps characterizing various stages of progression remain unclear. Studying a unique case of metastatic melanoma, we observed that cell lines derived from metachronous metastases arising over a decade retained a central core of genetic stability in spite of divergent phenotypes. In the present study, we expanded our previous observations comparing these autologous cell lines of clonal derivation with allogeneic ones and correlated array comparative genomic hybridization (aCGH) with gene expression profiling to determine their relative contribution to the dynamics of disease progression. aCGH and gene expression profiling were performed on autologous cell lines and allogeneic melanoma cell lines originating from other patients. A striking correlation existed between total extent of genetic imbalances, global transcriptional patterns, and cellular phenotypes. They did not follow a strict temporal progression but stemmed independently at various time points from a central core of genetic stability best explained according to the cancer stem cell hypothesis. Although their contribution was intertwined, genomic imbalances detectable by aCGH contributed only 25% of the transcriptional traits determining autologous tumor distinctiveness. Our study provides important insights about the dynamics of cancer progression and supports the development of targeted anticancer therapies aimed against stable genetic factors that are maintained throughout the end stage of disease. C1 [Sabatino, Marianna; Voiculescu, Sonia; Monaco, Alessandro; Selleri, Silvia; Marincola, Francesco M.; Wang, Ena] NCI, Infect Dis & Immunogenet Sect, Dept Transfus Med, Warren G Magnuson Clin Ctr,NIH, Bethesda, MD 20892 USA. [Zhao, Yingdong] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. [Robbins, Paul] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Karai, Laszlo] NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. [Nickoloff, Brian J.] Loyola Univ, Chicago Med Ctr, Skin Dis Res Program, Maywood, IL 60153 USA. [Maio, Michele] Univ Hosp Siena, Div Med Oncol & Immunotherapy, Dept Oncol, Ist Toscano Tumori, Siena, Italy. [Maio, Michele] Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, Dept Med Oncol, I-33081 Aviano, Italy. [Selleri, Silvia] Univ Milan, Dept Human Morphol, Milan, Italy. RP Wang, E (reprint author), NCI, Infect Dis & Immunogenet Sect, Dept Transfus Med, Warren G Magnuson Clin Ctr,NIH, Bldg 10,Room 1N224B,10 Ctr Dr, Bethesda, MD 20892 USA. EM ewang@mail.cc.nih.gov RI Monaco, Alessandro/O-5338-2015; OI Monaco, Alessandro/0000-0002-9941-7003; coral, sandra/0000-0002-1308-3082 NR 51 TC 23 Z9 25 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2008 VL 68 IS 1 BP 122 EP 131 DI 10.1158/0008-5472.CAN-07-1939 PG 10 WC Oncology SC Oncology GA 247IP UT WOS:000252072100019 PM 18172304 ER EF