FN Thomson Reuters Web of Science™ VR 1.0 PT J AU O'Brien, T Bonkovsky, H Pfeiffer, R Chung, R Everhart, J Shiffman, M Sninsky, J Morgan, T AF O'Brien, T. Bonkovsky, H. Pfeiffer, R. Chung, R. Everhart, J. Shiffman, M. Sninsky, J. Morgan, T. CA HALT-C Trial Grp TI ASSOCIATION OF IL28B GENOTYPE WITH VIROLOGICAL RESPONSE TO PEGYLATED-INTERFERON PLUS RIBAVIRIN IN PATIENTS WITH ADVANCED CHRONIC HEPATITIS C ENROLLED IN THE HALT-C TRIAL SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 14-18, 2010 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [O'Brien, T.; Pfeiffer, R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bonkovsky, H.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Chung, R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Everhart, J.] NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Shiffman, M.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Sninsky, J.] Celera, Alameda, CA USA. [Morgan, T.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, T.] VA Long Beach Healthcare Syst, Serv Gastroenterol, Long Beach, CA USA. EM obrient@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2010 VL 52 SU 1 BP S454 EP S454 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587UE UT WOS:000277018002374 ER PT J AU O'Brien, T Kohaar, I Pfeiffer, R Maeder, D Yeager, M Prokunina-Olsson, L Schadt, E AF O'Brien, T. Kohaar, I. Pfeiffer, R. Maeder, D. Yeager, M. Prokunina-Olsson, L. Schadt, E. TI HUMAN GENETIC VARIANTS LINKED TO CHRONIC HEPATITIS B ARE ASSOCIATED WITH EXPRESSION OF HLA-DPA1 AND HLA-DPB1 SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 45th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY APR 14-18, 2010 CL Vienna, AUSTRIA SP European Assoc Study Liver C1 [O'Brien, T.; Kohaar, I.; Pfeiffer, R.; Maeder, D.; Yeager, M.; Prokunina-Olsson, L.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Schadt, E.] Sage Bionetworks, Seattle, WA USA. [Schadt, E.] Pacific Biosci, Menlo Pk, CA USA. EM obrient@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2010 VL 52 SU 1 BP S284 EP S284 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587UE UT WOS:000277018001356 ER PT J AU Jones, MT Barlow, AEL Villarejo, M AF Jones, Melanie T. Barlow, Amy E. L. Villarejo, Merna TI Importance of Undergraduate Research for Minority Persistence and Achievement in Biology SO JOURNAL OF HIGHER EDUCATION LA English DT Article ID NONCOGNITIVE VARIABLES; RESEARCH EXPERIENCES; COLLEGE; STUDENTS; SCIENCE; OUTCOMES; PARTICIPATION; PERCEPTIONS; SCIENTISTS; ATTRITION C1 [Jones, Melanie T.] Univ Calif Davis, Dept Sociol, Davis, CA 95616 USA. [Barlow, Amy E. L.] Univ Calif Davis, Sch Educ, Davis, CA 95616 USA. [Villarejo, Merna] Univ Calif Davis, NIH, Minor Opportun Res MORE Evaluat Program, Davis, CA 95616 USA. RP Jones, MT (reprint author), Univ Calif Davis, Dept Sociol, 1 Shields Ave, Davis, CA 95616 USA. EM meljones@ucdavis.edu NR 60 TC 39 Z9 39 U1 1 U2 29 PU OHIO STATE UNIV PRESS PI COLUMBUS PA 1050 CARMACK RD, COLUMBUS, OH 43210 USA SN 0022-1546 J9 J HIGH EDUC JI J. High. Educ. PD JAN-FEB PY 2010 VL 81 IS 1 BP 82 EP 115 PG 34 WC Education & Educational Research SC Education & Educational Research GA 550FH UT WOS:000274113200004 ER PT J AU Park, HJ Cho, HJ Baek, JI Ben-Yosef, T Kwon, TJ Griffith, AJ Kim, UK AF Park, Hong-Joon Cho, Hyun-Ju Baek, Jeong-In Ben-Yosef, Tamar Kwon, Tae-Jun Griffith, Andrew J. Kim, Un-Kyung TI Evidence for a founder mutation causing DFNA5 hearing loss in East Asians SO JOURNAL OF HUMAN GENETICS LA English DT Article DE DFNA5; founder effect; hearing loss; mutation; non-syndromic ID CHINESE FAMILY; GENE; CONNEXIN-26; IMPAIRMENT AB Mutations in the DFNA5 gene are known to cause autosomal dominant non-syndromic hearing loss (ADNSHL). To date, five DFNA5 mutations have been reported, all of which were different in the genomic level. In this study, we ascertained a Korean family with autosomal dominant, progressive and sensorineural hearing loss and performed linkage analysis that revealed linkage to the DFNA5 locus on chromosome 7. Sequence analysis of DFNA5 identified a 3-bp deletion in intron 7 (c.991-15_991-13del) as the cause of hearing loss in this family. As the same mutation had been reported in a large Chinese family segregating DFNA5 hearing loss, we compared their DFNA5 mutation-linked haplotype with that of the Korean family. We found a conserved haplotype, suggesting that the 3-bp deletion is derived from a single origin in these families. Our observation raises the possibility that this mutation may be a common cause of autosomal dominant progressive hearing loss in East Asians. Journal of Human Genetics (2010) 55, 59-62; doi: 10.1038/jhg.2009.114; published online 13 November 2009 C1 [Cho, Hyun-Ju; Baek, Jeong-In; Kwon, Tae-Jun; Kim, Un-Kyung] Kyungpook Natl Univ, Dept Biol, Coll Nat Sci, Taegu 702701, South Korea. [Park, Hong-Joon] Soree Ear Clin, Seoul, South Korea. [Ben-Yosef, Tamar; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD USA. RP Kim, UK (reprint author), Kyungpook Natl Univ, Dept Biol, Coll Nat Sci, Taegu 702701, South Korea. EM kimuk@knu.ac.kr FU Korea government (MEST) [R01-2008-000-10431-0]; Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea [A080588]; National Institutes of Health intramural research fund [Z01-DC-000060] FX We are grateful to the family for their collaboration in this study. We also thank Dr Xiangyin Kong for providing Chinese samples. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (R01-2008-000-10431-0), a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea, A080588 (UKK) and the National Institutes of Health intramural research fund Z01-DC-000060. NR 12 TC 13 Z9 15 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD JAN PY 2010 VL 55 IS 1 BP 59 EP 62 DI 10.1038/jhg.2009.114 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 563UN UT WOS:000275160500012 PM 19911014 ER PT J AU Watford, WT Wang, CC Tsatsanis, C Mielke, LA Eliopoulos, AG Daskalakis, C Charles, N Odom, S Rivera, J O'Shea, J Tsichlis, PN AF Watford, Wendy T. Wang, Chun-Chi Tsatsanis, Christos Mielke, Lisa A. Eliopoulos, Aristides G. Daskalakis, Constantine Charles, Nicolas Odom, Sandra Rivera, Juan O'Shea, John Tsichlis, Philip N. TI Ablation of Tumor Progression Locus 2 Promotes a Type 2 Th Cell Response in Ovalbumin-Immunized Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; ANTI-IGE ANTIBODY; AIRWAY HYPERRESPONSIVENESS; TISSUE EOSINOPHILIA; CYTOKINE PRODUCTION; SIGNALING PATHWAYS; ALLERGIC-ASTHMA; MAST-CELLS; SERUM IGE AB The protein kinase encoded by the Tpl2 proto-oncogene regulates ERK activation and cytokine gene expression in macrophages in response to LPS and TNF-alpha. In this study we show that OVA-immunized Tpl2(-/-) mice express high levels of IgE and develop more severe bronchoalveolar eosinophilic inflammation than Tpl2(+/+) controls, when challenged with OVA intranasally. Bronchoalveolar exudates and supernatants of OVA-stimulated splenocytes from immunized Tpl2(-/-) mice express elevated levels of IL-4 and IL-5, suggesting that Tpl2 ablation promotes the Th2 polarization of the T cell response. Anti-CD3 stimulation of CD4(+) T cells of wildtype and Tpl2 knockout mice revealed that Tpl2 ablation gives rise to a cell autonomous T cell defect that is primarily responsible for the Th2 polarization of the T cell response to Ag. This observation was further supported by experiments addressing the expression of Th1 and Th2 cytokines in OVA-stimulated mixed cultures of CD4(+) T cells from Tpl2(+/+)/OT2 or Tpl2(-/-)/OT2 mice and dendritic cells from Tpl2(+/+) or Tpl2(-/-) mice. Further studies revealed that Th1 cells express significantly higher levels of Tpl2 than Th2 cells. As a result, Tpl2(-/-) Thl cells exhibit a stronger defect in ERK activation by anti-CD3 than Th2 cells and express low levels of T-bet. Given that the development of Thl and Th2 cells depends on positive feedback signals from the T cells, themselves, the functional defect of the Tpl2(-/-) Thl cells provides a mechanistic explanation for the T cell autonomous Th2 polarization in Tpl2(-/-) mice. The Journal of Immunology, 2010, 184: 105-113. C1 [Tsatsanis, Christos; Tsichlis, Philip N.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Watford, Wendy T.; Mielke, Lisa A.; Charles, Nicolas; Odom, Sandra; Rivera, Juan; O'Shea, John] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Wang, Chun-Chi; Daskalakis, Constantine] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Tsatsanis, Christos; Eliopoulos, Aristides G.] Univ Crete, Sch Med, Iraklion, Crete, Greece. RP Tsichlis, PN (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. EM ptsichlis@tuftsmedicalcenter.org RI Charles, Nicolas/P-5430-2014; OI Charles, Nicolas/0000-0002-5416-5834; Tsatsanis, Christos/0000-0003-1214-4151 FU Public Health Service Awards; National Institutes of Health [R01 CA38047, R01 CA095431, 5-T32-CA09662, 1 K22 AR53953-01]; Medical Research Council (UK) Career Development Award FX This work was supported by the Public Health Service Awards, National Institutes of Health R01 CA38047 and R01 CA095431 (all to P.N.T), National Institutes of Health Training Grant 5-T32-CA09662 (to C.C.W.), a Medical Research Council (UK) Career Development Award (to A.G.E.), and National Institutes of Health Grant 1 K22 AR53953-01 (to W.T.W.). NR 52 TC 17 Z9 17 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2010 VL 184 IS 1 BP 105 EP 113 DI 10.4049/jimmunol.0803730 PG 9 WC Immunology SC Immunology GA 535QL UT WOS:000272985300015 PM 19955521 ER PT J AU Bolton, DL Minang, JT Trivett, MT Song, KM Tuscher, JJ Li, Y Piatak, M O'Connor, D Lifson, JD Roederer, M Ohlen, C AF Bolton, Diane L. Minang, Jacob T. Trivett, Matthew T. Song, Kaimei Tuscher, Jennifer J. Li, Yuan Piatak, Michael, Jr. O'Connor, David Lifson, Jeffrey D. Roederer, Mario Ohlen, Claes TI Trafficking, Persistence, and Activation State of Adoptively Transferred Allogeneic and Autologous Simian Immunodeficiency Virus-Specific CD8(+) T Cell Clones during Acute and Chronic Infection of Rhesus Macaques SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO PERSISTENCE; LYMPHOCYTE RESPONSES; IMMUNE CONTROL; SIV INFECTION; LUNG AIRWAYS; KILLER-CELLS; MEMORY; HIV; ESCAPE; REPLICATION AB Despite multiple lines of evidence suggesting their involvement, the precise role of CD8(+) T cells in controlling HIV replication remains unclear. To determine whether CD8(+) T cells can limit retroviral replication in the absence of other immune responses, we transferred 1-1.3 X 10(9) allogeneic in vitro expanded SIV-specific CD8(+) T cell clones matched for the relevant restricting MHC-1 allele into rhesus macaques near the time of i.v. SIV challenge. Additionally, in vitro expanded autologous SIV-specific CD8(+) T cell clones were infused 4-9 mo postinfection. Infused cells did not appreciably impact acute or chronic viral replication. The partially MHC-matched allogeneic cells were not detected in the blood or most tissues after 3 d but persisted longer in the lungs as assessed by bronchoalveolar lavage (BAL). Autologotis cells transferred i.v. or i.p. were found in BAL and blood samples for up to 8 wk postinfusion. Interestingly, despite having a nominally activated phenotype (CD69(+)HLA-DR+), many of these cells persisted in the BAL without dividing. This suggests that expression of such markers by T cells at mucosal sites may not reflect recent activation, but may instead identify stable resident memory T cells. The lack of impact following transfer of such a large number of functional Ag-specific CD8(+) T cells on SIV replication may reflect the magnitude of the immune response required to contain the virus. The Journal of Immunology, 2010, 184: 303-314. C1 [Minang, Jacob T.; Trivett, Matthew T.; Li, Yuan; Piatak, Michael, Jr.; Lifson, Jeffrey D.; Ohlen, Claes] NCI Frederick, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21702 USA. [Bolton, Diane L.; Song, Kaimei; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Tuscher, Jennifer J.; O'Connor, David] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53711 USA. RP Ohlen, C (reprint author), NCI Frederick, AIDS & Canc Virus Program, SAIC Frederick, POB B, Frederick, MD 21702 USA. EM cohlen@ncifcrf.gov OI o'connor, david/0000-0003-2139-470X FU National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institutes of Health [N01-C0-12400, HHSN261200800001E] FX This work was supported by the intramural research programs of the National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health. This project has been funded in whole or in part with federal funds from the National Cancer Institute. National Institutes of Health, under contract numbers N01-C0-12400 and HHSN261200800001E. NR 61 TC 17 Z9 18 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2010 VL 184 IS 1 BP 303 EP 314 DI 10.4049/jimmunol.0902413 PG 12 WC Immunology SC Immunology GA 535QL UT WOS:000272985300035 PM 19949089 ER PT J AU Minang, JT Trivett, MT Bolton, DL Trubey, CM Estes, JD Li, Y Smedley, J Pung, R Rosati, M Jalah, R Pavlakis, GN Felber, BK Piatak, M Roederer, M Lifson, JD Ott, DE Ohlen, C AF Minang, Jacob T. Trivett, Matthew T. Bolton, Diane L. Trubey, Charles M. Estes, Jacob D. Li, Yuan Smedley, Jeremy Pung, Rhonda Rosati, Margherita Jalah, Rashmi Pavlakis, George N. Felber, Barbara K. Piatak, Michael, Jr. Roederer, Mario Lifson, Jeffrey D. Ott, David E. Ohlen, Claes TI Distribution, Persistence, and Efficacy of Adoptively Transferred Central and Effector Memory-Derived Autologous Simian Immunodeficiency Virus-Specific CD8(+) T Cell Clones in Rhesus Macaques during Acute Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AIDS VACCINE; IN-VIVO; IMMUNE-RESPONSES; DNA VACCINATION; MONOCLONAL-ANTIBODIES; MUCOSAL INFECTION; HIV-1 INFECTION; VIRAL ESCAPE; LYMPHOCYTES; MONKEYS AB Plasma viremia decreases coincident with the appearance of virus-specific CD8(+) T cells during acute HIV or SIV infection. This finding, along with demonstrations of viral mutational escape from CD8(+) T cell responses and transient increase in plasma viremia after depletion of CD8(+) T cells in SIV-infected monkeys strongly suggest a role for CD8(+) T cells in controlling HIV/SIV. However, direct quantitative or qualitative correlates between CD8(+) T cell activity and virus control have not been established. To directly assess the impact of large numbers of virus-specific CD8(+) T cells present at time of SIV infection, we transferred in vitro expanded autologous central and effector memory-derived Gag CM9-, Nef YY9-, and Vif WY8-specific CD8(+) T cell clones to acutely infected rhesus macaques. The cells persisted in PBMCs between 4 and 9 d, but were not detected in gut-associated lymphoid tissue or lymph nodes. Interestingly, a high frequency of the infused cells localized to the lungs, where they persisted at high frequency for >6 wk. Although persisting cells in the lungs were Ag reactive, there was no measurable effect on virus load. Sequencing of virus from the animal receiving Nef YY9-specific CD8(+) T cells demonstrated an escape mutation in this epitope <3 wk postinfection, consistent with immune selection pressure by the infused cells. These studies establish methods for adoptive transfer of autologous SIV-specific CD8(+) T cells for evaluating immune control during acute infection and demonstrate that infused cells retain function and persist for at least 2 mo in specific tissues. The Journal of Immunology, 2010, 184: 315-326. C1 [Ohlen, Claes] NCI Frederick, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21702 USA. [Smedley, Jeremy] SAIC Frederick, Lab Anim Sci Program, Frederick, MD 21702 USA. [Bolton, Diane L.; Pung, Rhonda; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Rosati, Margherita; Pavlakis, George N.] Natl Canc Inst Frederick, Human Retrovirus Sect, Frederick, MD 21702 USA. [Jalah, Rashmi; Felber, Barbara K.] Natl Canc Inst Frederick, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. RP Ohlen, C (reprint author), NCI Frederick, AIDS & Canc Virus Program, SAIC Frederick, POB B, Frederick, MD 21702 USA. EM cohlen@ncifcrf.gov OI Smedley, Jeremy/0000-0003-3369-4662 FU National Cancer Institute; National Institutes of Health [N01-C0-12400, HHSN261200800001E] FX This work was supported in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract numbers N01-C0-12400 and HHSN261200800001E. NR 63 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2010 VL 184 IS 1 BP 315 EP 326 DI 10.4049/jimmunol.0902410 PG 12 WC Immunology SC Immunology GA 535QL UT WOS:000272985300036 PM 19949091 ER PT J AU Salisch, NC Kaufmann, DE Awad, AS Reeves, RK Tighe, DP Li, Y Piatak, M Lifson, JD Evans, DT Pereyra, F Freeman, GJ Johnson, RP AF Salisch, Nadine C. Kaufmann, Daniel E. Awad, Amany S. Reeves, R. Keith Tighe, Daniel P. Li, Yuan Piatak, Michael, Jr. Lifson, Jeffrey D. Evans, David T. Pereyra, Florencia Freeman, Gordon J. Johnson, R. Paul TI Inhibitory TCR Coreceptor PD-1 Is a Sensitive Indicator of Low-Level Replication of SIV and HIV-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; T-CELL EXHAUSTION; MAJOR HISTOCOMPATIBILITY COMPLEX; CHRONIC VIRAL-INFECTION; CLASS-I MOLECULE; TYPE-1 ELITE CONTROLLERS; PROGRAMMED DEATH-1; RHESUS MACAQUES; NEF GENE; VACCINE PROTECTION AB Ongoing antigenic stimulation appears to be an important prerequisite for the persistent expression of programmed death 1 (PD-1), an inhibitory TCR coreceptor of the CD28 family. Although recent publications have emphasized the utility of PD-1 as a marker for dysfunctional T cells in chronic viral infections, its dependence on antigenic stimulation potentially renders it a sensitive indicator of low-level viral replication. To explore the antigenic threshold for the maintenance of PD-1 expression on virus-specific T cells, we compared PD-1 expression on virus-specific and memory T cell populations in controlled and uncontrolled SIV and HIV-1 infection. In both controlled live attenuated SIV infection in rhesus macaques and HIV-1 infection in elite controllers, elevated levels of PD-1 expression were observed on SIV- and HIV-1-specific CD8(+) T cells. However, in contrast to chronic wild-type SIV infection and uncontrolled HIV-1 infection, controlled SIV/HIV-1 infection did not result in increased expression of PD-1 on total memory T cells. PD-1 expression on SIV-specific CD8(+) T cells rapidly decreased after the emergence of CTL escape in cognate epitopes, but was maintained in the setting of low or undetectable levels of plasma viremia in live attenuated SIV-infected macaques. After inoculation of naive macaques with a single-cycle SIV, PD-1 expression on SIV-specific CD8(+) T cells initially increased, but was rapidly downregulated. These results demonstrate that PD-I can serve as a sensitive indicator of persistent, low-level virus replication and that generalized PD-1 expression on T lymphocytes is a distinguishing characteristic of uncontrolled lentiviral infections. The Journal of Immunology, 2010, 184: 476-487. C1 [Salisch, Nadine C.; Awad, Amany S.; Reeves, R. Keith; Johnson, R. Paul] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. [Evans, David T.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. [Kaufmann, Daniel E.; Tighe, Daniel P.; Pereyra, Florencia; Johnson, R. Paul] Massachusetts Gen Hosp, MIT, Ragon Inst, Charlestown, MA 02129 USA. [Kaufmann, Daniel E.; Tighe, Daniel P.; Pereyra, Florencia; Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. [Li, Yuan; Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, Sci Applicat Int Corp Frederick, AIDS & Canc Virus Program, Frederick, MD 21702 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Johnson, RP (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough Campus,Pine Hill Dr, Southborough, MA 01772 USA. EM paul_johnson@hms.harvard.edu FU National Institutes of Health [AI062412, AI071306, RR00168, AI063993, HL092565, AI080192, HHSN266200400088C]; International AIDS Vaccine Initiative; Center for HIV/AIDS Vaccine Immunology; HIV Vaccine Trials Network Early Career Investigator award [U19 Al 067854]; International HIV Controllers Study; National Cancer Institute; Elizabeth Glaser Pediatric AIDS Foundation FX This work was funded through National Institutes of Health Grants AI062412, AI071306, RR00168. AI063993, HL092565, HL092565, and AI080192, the International AIDS Vaccine Initiative, a Center for HIV/AIDS Vaccine Immunology and HIV Vaccine Trials Network Early Career Investigator award (U19 Al 067854) to R. K.R., and the International HIV Controllers Study. It was also supported in part with federal funds front the National Cancer Institute, National Institutes of Health, under Contract HHSN266200400088C. D.T.E. is air Elizabeth Glaser Scientist supported by the Elizabeth Glaser Pediatric AIDS Foundation. NR 76 TC 32 Z9 34 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2010 VL 184 IS 1 BP 476 EP 487 DI 10.4049/jimmunol.0902781 PG 12 WC Immunology SC Immunology GA 535QL UT WOS:000272985300053 PM 19949078 ER PT J AU Wrzesinski, C Paulos, CM Kaiser, A Muranski, P Palmer, DC Gattinoni, L Yu, ZY Rosenberg, SA Restifo, NP AF Wrzesinski, Claudia Paulos, Chrystal M. Kaiser, Andrew Muranski, Pawel Palmer, Douglas C. Gattinoni, Luca Yu, Zhiya Rosenberg, Steven A. Restifo, Nicholas P. TI Increased Intensity Lymphodepletion Enhances Tumor Treatment Efficacy of Adoptively Transferred Tumor-specific T Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE adoptive immunotherapy; total body irradiation ID CD45 MONOCLONAL-ANTIBODIES; TOTAL-BODY IRRADIATION; STEM-CELLS; IN-VIVO; METASTATIC MELANOMA; ANTITUMOR IMMUNITY; CANCER REGRESSION; REGULATORY-CELLS; IMMUNOTHERAPY; ANTIGEN AB Lymphodepletion before adoptive cell transfer (ACT)-based immunotherapies call enhance anti-tumor responses by augmenting innate immunity, by increasing access to homeostatic cytokines, and by depressing the numbers of regulatory T cells and myeloid-derived suppressor cells. Although it is clear that high-dose total body irradiation given together with, hematopoietic stem cell (HSC) transplantation effectively enhances ACT, the relationship between the intensity of lymphodepletion and tumor treatment efficacy has not been systematically studied. Using the pmel-1 Mouse model of self/tumor-reactive CD8(+) T cells, we observed a strong correlation between the intensity of the conditioning regimen and the efficacy of ACT-based treatments using linear regression analysis. This was the case for preparative total body irradiation administered either as a single dose (R(2) = 0.97, P<0.001) or in fractionated doses (R(2)=0.94, P<0.001). Increased amounts of preparative total body irradiation were directly correlated with progressively more favorable ratios of transferred tumor-reactive CD8(+) T cells toward endogenous cells with the potential for inhibitory activity including: CD4(+) cells (potentially T regulatory cells); Grl(+) cells (which are capable of functioning as myeloid-derived suppressor cells); and endogenous CD8(+) and natural killer 1.1(+) cells (that can act as "sinks" for homeostatic cytokines in the postablative setting). With increasing ablation, we also observed elevated lipopolysaccharide levels in the sera and heightened levels of systemic inflammatory cytokines. Thus, increased intensity lymphodepletion triggers enhanced tumor treatment efficacy and the benefits of high-dose total body irradiation must be titrated against its risks. C1 [Wrzesinski, Claudia; Paulos, Chrystal M.; Kaiser, Andrew; Muranski, Pawel; Palmer, Douglas C.; Gattinoni, Luca; Yu, Zhiya; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, 10 Ctr Dr Bldg CRC,Room 3-5762, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010; Kaiser, Andrew/C-2617-2012; Palmer, Douglas/B-9454-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU National Cancer Institute, National Institutes of Health (Bethesda, MD) FX Supported by the intramural program of the National Cancer Institute, National Institutes of Health (Bethesda, MD). NR 51 TC 108 Z9 113 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 2010 VL 33 IS 1 BP 1 EP 7 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 537RN UT WOS:000273131600001 PM 19952961 ER PT J AU ElKassar, N Gress, RE AF ElKassar, Nahed Gress, Ronald E. TI An overview of IL-7 biology and its use in immunotherapy SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Article ID RECEPTOR-GAMMA CHAIN; T-CELL DEVELOPMENT; DEFECTIVE LYMPHOID DEVELOPMENT; PI3K/AKT SIGNALING PATHWAY; MOUSE BONE-MARROW; MICE LACKING JAK3; INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; HOMEOSTATIC PROLIFERATION; THYMOCYTE DEVELOPMENT AB Interleukin (IL)-7 is required for T-cell development as well as for the survival and homeostasis of mature T-cells. In the thymus, the double negative (DN) CD4 globus pallidus > red nucleus was found. Phase symmetry analysis shows a difference between lateralized and symmetric PD. Conclusion: The symmetric phase model helps to analyze phase data with similar accuracy, but a greatly reduced tracing effort compared to individual tracing and also allows evaluating left-right phase symmetries. C1 [Grabner, Guenther; Trattnig, Siegfried] Med Univ Vienna, Dept Radiol, A-1090 Vienna, Austria. [Grabner, Guenther; Beisteiner, Roland; Trattnig, Siegfried] Med Univ Vienna, MR Ctr Excellence, A-1090 Vienna, Austria. [Haubenberger, Dietrich; Rath, Jakob; Beisteiner, Roland; Auff, Eduard] Med Univ Vienna, Dept Neurol, A-1090 Vienna, Austria. [Grabner, Guenther; Barth, Markus] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands. [Haubenberger, Dietrich] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Trattnig, S (reprint author), Med Univ Vienna, Dept Radiol, Spitalgasse 23, A-1090 Vienna, Austria. EM Siegfried.Trattnig@akhwien.at RI Barth, Markus/B-8446-2008 OI Barth, Markus/0000-0002-0520-1843 NR 20 TC 9 Z9 9 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2010 VL 31 IS 1 BP 215 EP 220 DI 10.1002/jmri.22013 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 540MO UT WOS:000273336100027 PM 20027591 ER PT J AU Reynolds, MM Saavedra, JE Showalter, BM Valdez, CA Shanklin, AP Oh, BK Keefer, LK Meyerhoff, ME AF Reynolds, Melissa M. Saavedra, Joseph E. Showalter, Brett M. Valdez, Carlos A. Shanklin, Anna P. Oh, Bong K. Keefer, Larry K. Meyerhoff, Mark E. TI Tailored synthesis of nitric oxide-releasing polyurethanes using O-2-protected diazeniumdiolated chain extenders SO JOURNAL OF MATERIALS CHEMISTRY LA English DT Article ID IMPROVED BLOOD COMPATIBILITY; IN-VIVO EVALUATION; SEGMENTED POLYURETHANES; CHEMICAL SENSORS; POLYMERIC FILMS; BIOCOMPATIBILITY; PIPERAZINE; GRAFTS; DONORS; MODEL AB Nitric oxide (NO) has been shown to exhibit significant anti-platelet activity and its release from polymer matrices has been already utilized to increase the biocompatibility of various blood-contacting devices. Herein, the details of a new synthetic approach for preparing NO-releasing diazeniumdiolated polyurethanes (PUs) are described. The method's utility is demonstrated by the incorporation of methoxymethyl- or sugar-protected pre-formed diazeniumdiolate moieties directly into chain extender diols which are then incorporated into the polyurethane backbone. This approach provides the ability to control the number of diazeniumdiolate groups incorporated into the polymer backbone, and hence the surface flux of NO that can ultimately be liberated from polymeric films prepared from the new PU materials. The method provides a means of covalently attaching diazeniumdiolate groups to polyurethanes in a form that resists dissociation of NO during processing but can be activated for spontaneous NO release via hydrolysis of the carbohydrate or methoxymethyl moieties under basic and acidic conditions, respectively. C1 [Reynolds, Melissa M.; Oh, Bong K.; Meyerhoff, Mark E.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21702 USA. [Showalter, Brett M.; Valdez, Carlos A.; Shanklin, Anna P.; Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Meyerhoff, ME (reprint author), Univ Michigan, Dept Chem, 930 N Univ Ave, Ann Arbor, MI 48109 USA. EM mmeyerho@umich.edu RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Institutes of Health (NIH) [EB-000783]; Intramural Research Program of the NIH; National Cancer Institute [NO1-CO-200800001]; Center for Cancer Research FX The authors are grateful for funding from the National Institutes of Health (NIH) through grant NIH EB-000783. Research was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, as well as National Cancer Institute contract NO1-CO-200800001 to SAIC. NR 36 TC 15 Z9 15 U1 0 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0959-9428 J9 J MATER CHEM JI J. Mater. Chem. PY 2010 VL 20 IS 15 BP 3107 EP 3114 DI 10.1039/c000152j PG 8 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 576NR UT WOS:000276152100027 PM 21132111 ER PT J AU Erez, O Romero, R Vaisbuch, E Kusanovic, JP Mazaki-Tovi, S Chaiworapongsa, T Gotsch, F Fareed, J Hoppensteadt, D Than, NG Yoon, BH Edwin, S Dong, Z Espinoza, J Mazor, M Hassan, SS AF Erez, Offer Romero, Roberto Vaisbuch, Edi Kusanovic, Juan Pedro Mazaki-Tovi, Shali Chaiworapongsa, Tinnakorn Gotsch, Francesca Fareed, Jawed Hoppensteadt, Debra Than, Nandor Gabor Yoon, Bo Hyun Edwin, Sam Dong, Zhong Espinoza, Jimmy Mazor, Moshe Hassan, Sonia S. TI High tissue factor activity and low tissue factor pathway inhibitor concentrations in patients with preterm labor SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE Thrombin generation; intra-amniotic inflammation; preterm delivery; parturition; TFPI/TF ratio ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELLS; FACTOR-XA; PLACENTAL PROTEIN-5; INTACT MEMBRANES; MESSENGER-RNA; MONONUCLEAR PHAGOCYTES; COAGULATION INHIBITOR; HEMOSTATIC CHANGES; BLOOD-COAGULATION AB Objective. Preterm labor (PTL) has been associated with an increased thrombin generation in the maternal circulation and amniotic fluid. Tissue factor (TF) is a potent initiator of the coagulation cascade, which can trigger the hemostatic system to generate thrombin. The aims of this study were to determine whether spontaneous PTL with intact membranes is associated with changes in the maternal plasma concentrations and activity of TF as well as tissue factor pathway inhibitor (TFPI). Methods. This cross-sectional study included women in the following groups: (1) normal pregnancies (n = 86); (2) term pregnancies in spontaneous labor (TIL) (n = 67) and not in labor (TNL) (n = 88). and (3) patients with spontaneous PTL and intact membranes (n = 136) that were classified into three sub-groups: (a) PTL without intra-amniotic infection and/or inflammation (IAI) who delivered at term (n = 49); (b) PTL without IAI who delivered preterm. (n = 54); and (c) PTL with IAI who delivered preterm (n = 33). Plasma concentrations of TF and TFPI were measured by ELISA, and their activity was measured by chromogenic assays. Non-parametric statistics were used for analysis. Results. (1) Among women at term, those with spontaneous labor had a higher median maternal plasma TF and a lower median TFPI concentration than those without labor. (2) Patients with PTL had a significantly lower median maternal plasma TFPI concentration than that of normal pregnant women, regardless of the presence of IAI. (3) There was no significant difference in the median maternal plasma TF concentration between patients with a normal pregnancy and those with PTL. (4) In contrast, the median maternal plasma TF activity was higher among patients with PTL than in women with normal pregnancies, regardless of the presence of IAI or preterm delivery. (5) However, maternal plasma TFPI activity did not differ among the study groups. Conclusion. Women with preterm parturition, in contrast to those in labor at term, have a higher TF activity and a lower TFPI concentration, without a significant change in the median maternal plasma TF concentration. These observations suggest that the increased thrombin generation reported in patients with PTL may be the result of activation of the extrinsic pathway of the coagulation cascade. In addition, the increased thrombin generation reported in patients with PTL could be due to insufficient anti-coagulation, as reflected by the low maternal plasma TFPI concentration. C1 [Erez, Offer] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Gotsch, Francesca; Than, Nandor Gabor; Edwin, Sam; Dong, Zhong; Espinoza, Jimmy; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Espinoza, Jimmy; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Fareed, Jawed; Hoppensteadt, Debra] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. [Mazor, Moshe] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Obstet & Gynecol, Soroka Univ,Med Ctr, Beer Sheva, Israel. RP Erez, O (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM oerez@med.wayne.edu; prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 105 TC 21 Z9 21 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JAN PY 2010 VL 23 IS 1 BP 23 EP 33 DI 10.3109/14767050902994770 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 553CZ UT WOS:000274344100004 PM 19883261 ER PT J AU Kusanovic, JP Romero, R Chaiworapongsa, T Mittal, P Mazaki-Tovi, S Vaisbuch, E Erez, O Gotsch, F Than, NG Edwin, SS Pacora, P Jodicke, C Yeo, L Hassani, SS AF Kusanovic, Juan Pedro Romero, Roberto Chaiworapongsa, Tinnakorn Mittal, Pooja Mazaki-Tovi, Shali Vaisbuch, Edi Erez, Offer Gotsch, Francesca Than, Nandor Gabor Edwin, Sam S. Pacora, Percy Jodicke, Cristiano Yeo, Lami Hassani, Sonia S. TI Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Preterm labor; preterm delivery; preterm prelabor rupture of membranes; PPROM; pregnancy; amniocentesis; microbial invasion of the amniotic cavity; MIAC; cytokines; chorioamnionitis ID NECROSIS-FACTOR-ALPHA; MYELOID CELLS-1; SEPTIC SHOCK; INTRAUTERINE INFECTION; EXPRESSION PATTERNS; CEREBRAL-PALSY; BRONCHOPULMONARY DYSPLASIA; CYTOKINES INTERLEUKIN-6; INFLAMMATORY RESPONSES; CLINICAL-SIGNIFICANCE AB Objective. Intra-amniotic infection/inflammation (IAI) is one of the most important mechanisms of disease in preterm birth. Triggering receptor expressed on myeloid cells (TREM)- 1 is a transmembrane glycoprotein expressed by neutrophils, macrophages and mature monocytes. TREM-1 is upregulated in biological fluids and tissues infected by Gram (+) and Gram (-) bacteria and fungi, amplifies the production of pro-inflammatory cytokines and chemokines, and its soluble form (sTREM-1) is released in the presence of infection. The aim of this study was to determine the effect of gestational age, parturition (term and preterm) and IAI in the amniotic fluid (AF) concentrations of sTREM-1. Study design. This cross-sectional study included 434 patients in the following groups: (1) mid-trimester of pregnancy (14-18 weeks, n = 38); (2) normal pregnant women at term with (n = 39) and without (n = 39) labor; (3) patients with spontaneous preterm labor (PTL) and intact membranes classified into: (a) PTL who delivered at term (n = 99); (b) PTL who delivered preterm (<37 weeks gestation) without IAI (n = 80),- and (c) PTL with IAI (n = 59); and (4) women with preterm prelabor rupture of membranes (PROM) with (n = 40) and without (n = 40) IAI. The AF concentration of sTREM-1 was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results. (1) sTREM-1 was detected in all the AF samples; (2) the median AF sTREM-1 concentration at term was higher than in the mid-trimester (4277.6 pg/ml vs. 1140.4 pg/ml; p < 0.001); (3) among patients with PTL, the median AF sTREM-1 concentration was higher in patients with IAI than in those without IAI (6154.4 pg/ml vs. 3282.8 pg/ml; p < 0.001) and those with PTL who delivered at term (6154.4 pg/ml vs. 2794 pg/ml; p < 0.001); (4) patients with preterm PROM with IAI had a higher median AF sTREM-1 concentration than those without IAI (7893.1 pg/ml vs. 3386.6 pg/ml; p < 0.001); (5) no differences were observed in the median AF sTREM-1 concentration between patients with spontaneous labor at term and those at term not in labor (4712.4 pg/ml vs. 4277.6 pg/ml; respectively p = 0.4); and 6) an AF sTREM-1 concentration >= 6416 pg/ml (derived from a ROC curve) had a sensitivity of 72% and a specificity of 89% for the diagnosis of intra-amniotic infection. Conclusions. sTREM-1 is a physiologic constituent of the AF, and its concentration: (1) is significantly elevated in the presence of IAI; (2) increases with advancing gestation; and (3) does not change in the presence of spontaneous labor at term. We propose that sTREM-1 play a role in the innate immune response against intra-amniotic infection. C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Kusanovic, Juan Pedro; Romero, Roberto; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Gotsch, Francesca; Than, Nandor Gabor; Edwin, Sam S.; Pacora, Percy; Jodicke, Cristiano; Yeo, Lami; Hassani, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Kusanovic, Juan Pedro; Romero, Roberto; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Jodicke, Cristiano; Yeo, Lami; Hassani, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM jkusanov@med.wayne.edu; prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 79 TC 25 Z9 25 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JAN PY 2010 VL 23 IS 1 BP 34 EP 47 DI 10.3109/14767050903009248 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 553CZ UT WOS:000274344100005 PM 19591072 ER PT J AU Kusanovic, JP Romero, R Gotsch, F Mittal, P Erez, O Kim, CJ Hassan, SS Espinoza, J Yeo, L AF Kusanovic, Juan Pedro Romero, Roberto Gotsch, Francesca Mittal, Pooja Erez, Offer Kim, Chong Jai Hassan, Sonia S. Espinoza, Jimmy Yeo, Lami TI Discordant placental echogenicity: a novel sign of impaired placental perfusion in twin-twin transfusion syndrome? SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Placenta; monochorionic; TTTS; angiogenesis; endoglin; sVEGFR-1; placental growth factor; anti-angiogenic state AB Twin-twin transfusion syndrome (TTTS) is present in approximately 5-15% of monochorionic-diamniotic twin pregnancies. A chronic blood flow imbalance through placental vascular anastomoses from the donor to the recipient twin is considered the pathophysiologic mechanism responsible for the development of TTTS. Discordant echogenicity between the donor and recipient placenta has been proposed in a previous case report as an additional sonographic sign of TTTS. Here, we present a case of TTTS with discordant placental echogenicity characterized by a hyperechoic and thicker placental side in the donor twin associated with reduced vascular Doppler signals, histologic lesions suggestive of ischemic changes, and overexpression of anti-angiogenic factors. C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Kusanovic, Juan Pedro; Romero, Roberto; Gotsch, Francesca; Mittal, Pooja; Erez, Offer; Kim, Chong Jai; Hassan, Sonia S.; Espinoza, Jimmy; Yeo, Lami] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Kusanovic, Juan Pedro; Romero, Roberto; Mittal, Pooja; Erez, Offer; Hassan, Sonia S.; Espinoza, Jimmy; Yeo, Lami] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 6 TC 7 Z9 8 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD JAN PY 2010 VL 23 IS 1 BP 103 EP 106 DI 10.3109/14767050903005873 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 553CZ UT WOS:000274344100014 PM 19626497 ER PT J AU Karev, GP AF Karev, Georgiy P. TI On mathematical theory of selection: continuous time population dynamics SO JOURNAL OF MATHEMATICAL BIOLOGY LA English DT Article DE Selection system; Dynamics of distribution; The Price equation; Inhomogeneous logistic model; Replicator equation ID HETEROGENEITY; CHARACTERS; SURVIVAL; FITTEST; MODELS AB Mathematical theory of selection is developed within the frameworks of general models of inhomogeneous populations with continuous time. Methods that allow us to study the distribution dynamics under natural selection and to construct explicit solutions of the models are developed. All statistical characteristics of interest, such as the mean values of the fitness or any trait can be computed effectively, and the results depend in a crucial way on the initial distribution. The developed theory provides an effective method for solving selection systems; it reduces the initial complex model to a special system of ordinary differential equations (the escort system). Applications of the method to the Price equations are given; the solutions of some particular inhomogeneous Malthusian, Ricker and logistic-like models used but not solved in the literature are derived in explicit form. C1 NIH, Lockheed Martin MSD, Bethesda, MD 20894 USA. RP Karev, GP (reprint author), NIH, Lockheed Martin MSD, Bldg 38A,Rm 5N511N,8600 Rockville Pike, Bethesda, MD 20894 USA. EM karev@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 39 TC 24 Z9 25 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0303-6812 J9 J MATH BIOL JI J. Math. Biol. PD JAN PY 2010 VL 60 IS 1 BP 107 EP 129 DI 10.1007/s00285-009-0252-0 PG 23 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 494XW UT WOS:000269854000006 PM 19283384 ER PT J AU Scherer, ML Nalls, MA Pawlikowska, L Ziv, E Mitchell, G Huntsman, S Hu, D Sutton-Tyrrell, K Lakatta, EG Hsueh, WC Newman, AB Tandon, A Kim, L Kwok, PY Sung, A Li, R Psaty, B Reiner, AP Harris, T AF Scherer, M. L. Nalls, M. A. Pawlikowska, L. Ziv, E. Mitchell, G. Huntsman, S. Hu, D. Sutton-Tyrrell, K. Lakatta, E. G. Hsueh, W-C Newman, A. B. Tandon, A. Kim, L. Kwok, P-Y Sung, A. Li, R. Psaty, B. Reiner, A. P. Harris, T. TI Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID BLOOD-PRESSURE INDEX; CARDIOVASCULAR HEALTH; AFRICAN-AMERICAN; LINKAGE DISEQUILIBRIUM; POPULATION-STRUCTURE; BRACHIAL INDEX; ADMIRED POPULATIONS; UNITED-STATES; RISK; GENES AB Background Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and has a higher prevalence in African Americans than Caucasians. Ankle-arm index (AAI) is the ratio of systolic blood pressure in the leg to that in the arm, and, when low, is a marker of PAD. Methods The authors used an admixture mapping approach to search for genetic loci associated with low AAI. Using data from 1040 African American participants in the observational, population based Health, Aging, and Body Composition Study who were genotyped at 1322 single nucleotide polymorphisms (SNPs) that are informative for African versus European ancestry and span the entire genome, we estimated genetic ancestry in each chromosomal region and then tested the association between AAI and genetic ancestry at each locus. Results The authors found a region of chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African American participants in the observational, population based Cardiovascular Health Study were genotyped at rs9665943 to test the reproducibility of this association, and this association was also statistically significant (odds ratio (OR) for homozygous African genotype 1.59, 95% confidence interval (CI) 1.12 to 2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in both populations, and was also found to be significantly associated with low AAI in both populations (OR for homozygous African genotype 1.89, 95% CI 1.29 to 2.76). Conclusion This study identifies a novel region of chromosome 11 representing an area with a potential candidate gene associated with PAD in African Americans. C1 [Scherer, M. L.; Kim, L.; Harris, T.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Nalls, M. A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Pawlikowska, L.; Ziv, E.; Huntsman, S.; Hu, D.; Hsueh, W-C; Kwok, P-Y; Sung, A.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Pawlikowska, L.; Ziv, E.; Kwok, P-Y; Sung, A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Mitchell, G.] Cardiovasc Engn Inc, Waltham, MA USA. [Huntsman, S.; Hu, D.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. [Sutton-Tyrrell, K.; Newman, A. B.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Lakatta, E. G.] NIA, Cardiovasc Sci Lab, Bethesda, MD 20892 USA. [Newman, A. B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Tandon, A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Tandon, A.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Kwok, P-Y] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Li, R.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Psaty, B.; Reiner, A. P.] Univ Washington, Sch Publ Hlth & Community Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. RP Harris, T (reprint author), NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave,MSC, Bethesda, MD 20892 USA. EM harris99@nia.nih.gov RI Kwok, Pui-Yan/F-7725-2014; Ziv, Elad/L-5396-2014; Newman, Anne/C-6408-2013 OI Kwok, Pui-Yan/0000-0002-5087-3059; Newman, Anne/0000-0002-0106-1150 FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295]; National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of Neurological Disorders and Stroke; Burroughs Wellcome Career Development Award in the Biomedical Sciences; NCI [K22 CA109351]; Department of Defense [BC030551]; NIH/NIA [U19 AG23122] FX The research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, as well as the Intramural Research Program of the National Institute on Aging, contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 with additional contribution from the National Institute of Neurological Disorders and Stroke. DR was supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences. EZ's effort was supported by a career development award from the NCI (K22 CA109351), the Department of Defense Breast Cancer Research Program (BC030551), and the NIH/NIA (U19 AG23122). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 40 TC 7 Z9 7 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2010 VL 47 IS 1 BP 1 EP 7 DI 10.1136/jmg.2008.064808 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 543MC UT WOS:000273581000001 PM 19586928 ER PT J AU Doherty, D Parisi, MA Finn, LS Gunay-Aygun, M Al-Mateen, M Bates, D Clericuzio, C Demir, H Dorschner, M van Essen, AJ Gahl, WA Gentile, M Gorden, NT Hikida, A Knutzen, D Ozyurek, H Phelps, I Rosenthal, P Verloes, A Weigand, H Chance, PF Dobyns, WB Glass, IA AF Doherty, D. Parisi, M. A. Finn, L. S. Gunay-Aygun, M. Al-Mateen, M. Bates, D. Clericuzio, C. Demir, H. Dorschner, M. van Essen, A. J. Gahl, W. A. Gentile, M. Gorden, N. T. Hikida, A. Knutzen, D. Ozyurek, H. Phelps, I. Rosenthal, P. Verloes, A. Weigand, H. Chance, P. F. Dobyns, W. B. Glass, I. A. TI Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis) SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MECKEL-GRUBER-SYNDROME; FAMILIAL JUVENILE NEPHRONOPHTHISIS; RECESSIVE MENTAL-RETARDATION; SYNDROME-RELATED DISORDERS; BARDET-BIEDL-SYNDROME; OCULO-RENAL SYNDROMES; MOLAR TOOTH SIGN; CENTROSOMAL PROTEIN; DIAGNOSTIC-CRITERIA; POLYCYSTIC KIDNEY AB Objective To identify genetic causes of COACH syndrome Background COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). Methods In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. Results 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). Conclusions Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L. C1 [Doherty, D.; Finn, L. S.; Bates, D.; Dorschner, M.; Gorden, N. T.; Hikida, A.; Knutzen, D.; Phelps, I.; Chance, P. F.; Glass, I. A.] Univ Washington, Seattle, WA 98195 USA. [Parisi, M. A.; Gunay-Aygun, M.; Gahl, W. A.] NIH, Bethesda, MD 20892 USA. [Al-Mateen, M.] Mary Bridge Pediat Neurol, Tacoma, WA USA. [Clericuzio, C.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Demir, H.] Hacettepe Univ, Ankara, Turkey. [van Essen, A. J.] Univ Groningen, Groningen, Netherlands. [Gentile, M.] IRCCS Bellis Hosp, Castellana Grotte, Italy. [Ozyurek, H.] Ondokuz Mayis Univ, Samsun, Turkey. [Rosenthal, P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Verloes, A.] Hop Robert Debre, F-75019 Paris, France. [Weigand, H.] Univ Munich, Munich, Germany. [Dobyns, W. B.] Univ Chicago, Chicago, IL 60637 USA. RP Doherty, D (reprint author), Univ Washington, Box 356320,1959 NE Pacific St, Seattle, WA 98195 USA. EM ddoher@u.washington.edu OI , Alain/0000-0003-4819-0264; Dobyns, William/0000-0002-7681-2844 FU US National Institutes of Health [K23NS45832, K24HD46712, NCRR 5KL2RR025015, R01NS050375]; March of Dimes Endowment for Healthier Babies; Ames Endowment Fund; Allan and Phyllis Treuer Endowed Chair FX This work was supported by the US National Institutes of Health (grants K23NS45832 to MAP, K24HD46712 to IAG, NCRR 5KL2RR025015 to DD, R01NS050375 to WBD), the March of Dimes Endowment for Healthier Babies (DD, MAP, and IAG), the Ames Endowment Fund at Seattle Children's Hospital (IAG), and the Allan and Phyllis Treuer Endowed Chair (PFC) at Seattle Children's Hospital. NR 76 TC 35 Z9 39 U1 4 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2010 VL 47 IS 1 BP 8 EP 21 DI 10.1136/jmg.2009.067249 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 543MC UT WOS:000273581000002 PM 19574260 ER PT J AU Dowling, EC Klabunde, C Patnick, J Ballard-Barbash, R AF Dowling, Emily C. Klabunde, Carrie Patnick, Julietta Ballard-Barbash, Rachel CA ICSN TI Breast and cervical cancer screening programme implementation in 16 countries SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID NETHERLANDS AB Objectives There is a continuing need to monitor and evaluate the impact of organized screening programmes on cancer incidence and mortality. We report results from a programme assessment conducted within the International Cancer Screening Network (ICSN) to understand the characteristics of cervical screening programmes within countries that have established population-based breast cancer screening programmes. Methods In 2007-2008, we asked 26 ICSN country representatives to complete a web-based survey that included questions on breast and cervical cancer screening programmes. We summarized information from 16 countries with both types of organized programmes. Results In 63% of these countries, the organization of the cervical cancer screening programme was similar to that of the breast cancer screening programme in the same country. There were differences in programme characteristics, including year established (1962-2003 cervical; 1986-2002 breast) and ages covered (15-70+ cervical; 40-75+ breast). Adoption of new screening technologies was evident (44% liquid-based Pap tests; 13% human papillomavirus (HPV)-triage tests cervical; 56% digital mammography breast). There was wide variation in participation rates for both programme types (<4-80% cervical; 12-88% breast), and participation rates tended to be higher for cervical (70-80%) than for breast (60-70%) cancer screening programmes. Eleven ICSN member countries had approved the HPV vaccine and five more were considering its use in their organized programmes. Conclusion Overall, there were similarities and differences in the organization of breast and cervical cancer screening programmes among ICSN countries. This assessment can assist established and new screening programmes in understanding the organization and structure of cancer screening programmes. C1 [Dowling, Emily C.; Klabunde, Carrie; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Patnick, Julietta] Natl Hlth Serv Canc Screening Programmes, Sheffield, S Yorkshire, England. RP Dowling, EC (reprint author), 6130 Execut Blvd,Room 4111,MSD 7344,EPN 4005, Bethesda, MD 20892 USA. EM dowlinge@mail.nih.gov OI Lynge, Elsebeth/0000-0003-4785-5236 NR 20 TC 61 Z9 61 U1 1 U2 6 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2010 VL 17 IS 3 BP 139 EP 146 DI 10.1258/jms.2010.010033 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 694GU UT WOS:000285283800006 PM 20956724 ER PT J AU Chernomordik, V Gandjbakhche, AH Weiss, GH Dagdug, L AF Chernomordik, Victor Gandjbakhche, Amir H. Weiss, George H. Dagdug, Leonardo TI Effects of anisotropy of the turbid media on the photon penetration depth SO JOURNAL OF MODERN OPTICS LA English DT Article DE anisotropic optical media; photon penetration; random walk model; moments of maximum penetration ID LIGHT-PROPAGATION; MIGRATION; DIFFUSION AB Biomedical applications of near infrared radiation (NIR) techniques (i.e. based on light wavelengths roughly between 400 and 1100 nm) require that a preliminary estimate of the tissue volume being investigated be found. One possible estimate is the depth to which a photon penetrates a tissue before eventually emerging at a separating plane at a given time. A simple model for this problem can be based on a lattice random walk and was initially analyzed when the associated optical coefficients are isotropic with respect to the geometrical configuration. Here we include the effects of anisotropy in the optical coefficients, finding that at long times the statistical properties of the depth of penetration can be accounted for by very simple scaling factors while at short times the anisotropy effects can be quite noticeable. C1 [Weiss, George H.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Chernomordik, Victor; Gandjbakhche, Amir H.] NICHHD, Sect Analyt & Funct Biophoton, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. [Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Phys, Mexico City 09340, DF, Mexico. RP Weiss, GH (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM weissgh@mail.nih.gov FU National Institute of Child Health and Human Development; Center for Information Technology, National Institutes of Health FX This research was supported by the Intramural Research Programs of the National Institute of Child Health and Human Development and the Center for Information Technology, National Institutes of Health. NR 18 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0950-0340 J9 J MOD OPTIC JI J. Mod. Opt. PY 2010 VL 57 IS 20 BP 2048 EP 2053 AR PII 928669917 DI 10.1080/09500340.2010.519828 PG 6 WC Optics SC Optics GA 689VT UT WOS:000284959300005 PM 23049167 ER PT J AU Chen, RB Holmes, EC AF Chen, Rubing Holmes, Edward C. TI Hitchhiking and the Population Genetic Structure of Avian Influenza Virus SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE Avian influenza virus; Phylogeny; Hitchhiking; Reassortment; Natural selection ID A VIRUSES; WILD BIRDS; INTERSPECIES TRANSMISSION; HEMAGGLUTININ GENES; EVOLUTION; DYNAMICS; ECOLOGY AB Previous studies have revealed a major difference in the phylogenetic structure, extent of genetic diversity, and selection pressure between the surface glycoproteins and internal gene segments of avian influenza viruses (AIV) sampled from wild birds. However, what evolutionary processes are responsible for these strikingly different evolutionary patterns is unclear. To address this issue, we estimated the rate of evolutionary change and time of origin of each segment of AIV sampled globally. Strikingly, the internal segments of the sampled AIV strains possess common ancestors that existed less than 200 years ago. Similarly recent times of origin were observed for each of the individual subtypes within the HA, NA, and NS gene segments. Such a shallow history of genetic diversity suggests an evolutionary model in which the genetic structure of AIV is shaped by a combination of occasional selective sweeps in the HA and NA (and possibly NS) segments, coupled with transient genetic linkage to the internal gene segments. C1 [Chen, Rubing; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. EM ech15@psu.edu RI Chen, Rubing/F-2314-2011; Chen, Rubing/A-2276-2010; OI Holmes, Edward/0000-0001-9596-3552 FU NIH [GM080533] FX This study was funded in part by NIH grant GM080533. We thank two reviewers for useful comments. NR 33 TC 23 Z9 25 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD JAN PY 2010 VL 70 IS 1 BP 98 EP 105 DI 10.1007/s00239-009-9312-8 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 554US UT WOS:000274461300009 PM 20041240 ER PT J AU Nemeth, K Mayer, B Mezey, E AF Nemeth, Krisztian Mayer, Balazs Mezey, Eva TI Modulation of bone marrow stromal cell functions in infectious diseases by toll-like receptor ligands SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE Adult stem cells; TLR; Bone marrow; Immunology; Infectiology; Antiviral ID MESENCHYMAL STEM-CELLS; RESPONSES; TRANSPLANTATION; SEPSIS; VIRUS AB Bone marrow-derived stromal cells (BMSCs, or as they are frequently referred to as mesenchymal stem cells) have been long known to support hematopoiesis and to regenerate bone, cartilage, and adipose tissue. In the last decade, however, a vast amount of data surfaced in the literature to suggest new roles for these cells including tissue regeneration and immunomodulation. A great number of review articles appeared that summarize these new data and focus on different aspects of the physiology of these cells. In this present short review, we will try to summarize the available data based on both mouse and human cells describing how the function of BMSCs might be affected by an infectious environment. These data strongly support the idea that different toll-like receptor ligands can lead to substantial changes in the function of BMSCs that affect their proliferation, apoptosis, migration, and their production and release of immunomodulatory factors. C1 [Nemeth, Krisztian; Mayer, Balazs; Mezey, Eva] NIDCR, NIH, CSDB, Bethesda, MD 20892 USA. RP Nemeth, K (reprint author), NIDCR, NIH, CSDB, Bldg 49,Rm 5A-76,49 Convent Dr, Bethesda, MD 20892 USA. EM nemethk@mail.nih.gov; mezeye@mail.nih.gov RI Mayer, Balazs/B-7864-2013 OI Mayer, Balazs/0000-0003-3577-3823 FU Division of Intramural Research of the NIDCR; NIH FX This research was supported by the Division of Intramural Research of the NIDCR, Intramural Research Program of the NIH. NR 33 TC 34 Z9 35 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD JAN PY 2010 VL 88 IS 1 BP 5 EP 10 DI 10.1007/s00109-009-0523-7 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 544OT UT WOS:000273668400002 PM 19756450 ER PT J AU Norden, AD Raizer, JJ Abrey, LE Lamborn, KR Lassman, AB Chang, SM Yung, WKA Gilbert, MR Fine, HA Mehta, M DeAngelis, LM Cloughesy, TF Robins, HI Aldape, K Dancey, J Prados, MD Lieberman, F Wen, PY AF Norden, Andrew D. Raizer, Jeffrey J. Abrey, Lauren E. Lamborn, Kathleen R. Lassman, Andrew B. Chang, Susan M. Yung, W. K. Alfred Gilbert, Mark R. Fine, Howard A. Mehta, Minesh DeAngelis, Lisa M. Cloughesy, Timothy F. Robins, H. Ian Aldape, Kenneth Dancey, Janet Prados, Michael D. Lieberman, Frank Wen, Patrick Y. TI Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Meningioma; Erlotinib; Gefitinib; Epidermal growth factor receptor inhibitor ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; CHEMOTHERAPY; EXPRESSION; GLIOMAS; MULTICENTER AB There are no established treatments for recurrent meningioma when surgical and radiation options are exhausted. The epidermal growth factor receptor (EGFR) is often over-expressed in meningiomas and may promote tumor growth. In open label, single arm phase II studies of the EGFR inhibitors gefitinib (NABTC 00-01) and erlotinib (NABTC 01-03) for recurrent malignant gliomas, we included exploratory subsets of recurrent meningioma patients. We have pooled the data and report the results here. Patients with recurrent histologically confirmed meningiomas with no more than 2 previous chemotherapy regimens were treated with gefitinib 500 mg/day or erlotinib 150 mg/day until tumor progression or unacceptable toxicity. Twenty-five eligible patients were enrolled with median age 57 years (range 29-81) and median Karnofsky performance status (KPS) score 90 (range 60-100). Sixteen patients (64%) received gefitinib and 9 (36%) erlotinib. Eight patients (32%) had benign tumors, 9 (36%) atypical, and 8 (32%) malignant. For benign tumors, the 6-month progression-free survival (PFS6) was 25%, 12-month PFS (PFS12) 13%, 6-month overall survival (OS6) 63%, and 12-month OS (OS12) 50%. For atypical and malignant tumors, PFS6 was 29%, PFS12 18%, OS6 71%, and OS12 65%. The PFS and OS were not significantly different by histology. There were no objective imaging responses, but 8 patients (32%) maintained stable disease. Although treatment was well-tolerated, neither gefitinib nor erlotinib appear to have significant activity against recurrent meningioma. The role of EGFR inhibitors in meningiomas is unclear. Evaluation of multi-targeted inhibitors and EGFR inhibitors in combination with other targeted molecular agents may be warranted. C1 [Norden, Andrew D.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Raizer, Jeffrey J.] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Abrey, Lauren E.; Lassman, Andrew B.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Yung, W. K. Alfred; Gilbert, Mark R.; Aldape, Kenneth] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Fine, Howard A.] Natl Canc Inst, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Mehta, Minesh; Robins, H. Ian] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Neurooncol Program, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dancey, Janet] Natl Canc Inst, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Lieberman, Frank] Univ Pittsburgh, Neurooncol Program, Inst Canc, Pittsburgh, PA 15232 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 44 Binney St,SW430B, Boston, MA 02115 USA. EM pwen@partners.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NABTC [CA62399, CA62422]; GCRC [M01-RR00079, CA62412, CA16672, U01CA62407-08, U01CA62421-08, M01 RR03186, U01CA62405, M01-RR00056, U01 CA62399, M01-RR0865]; [5-U01CA62399-09] FX Grant Support: 5-U01CA62399-09 (J. J. Raizer, L. E. Abrey, A. B. Lassman and L. M. DeAngelis), NABTC # CA62399 and Member # CA62422, GCRC Grant # M01-RR00079 (S. M. Chang, K. R. Lamborn and M. D. Prados); CA62412, GCRC Grant # CA16672 (W. K. A. Yung and M. R. Gilbert); U01CA62407-08 (P. Y. Wen), U01CA62421-08, GCRC Grant # M01 RR03186 (M. Mehta and I. H. Robins); U01CA62405, GCRC Grant # M01-RR00056 (F. Lieberman); U01 CA62399, GCRC Grant # M01-RR0865 (T. F. Cloughesy). NR 28 TC 63 Z9 64 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2010 VL 96 IS 2 BP 211 EP 217 DI 10.1007/s11060-009-9948-7 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 546DK UT WOS:000273788600008 PM 19562255 ER PT J AU Matsumoto, M Kondo, S Usdin, TB Ueda, H AF Matsumoto, Misaki Kondo, Saori Usdin, Ted B. Ueda, Hiroshi TI Parathyroid hormone 2 receptor is a functional marker of nociceptive myelinated fibers responsible for neuropathic pain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cyclic AMP-dependent protein kinase; neuropathic pain; nociception; PTH2 receptor; TIP39 ID PRIMARY SENSORY NEURONS; VIVO SIGNAL-TRANSDUCTION; SCIATIC-NERVE INJURY; TUBEROINFUNDIBULAR PEPTIDE; NOCICEPTIN/ORPHANIN FQ; 39 RESIDUES; PERIPHERAL MECHANISMS; MOLECULAR-MECHANISMS; CAPSAICIN TREATMENT; SODIUM-CHANNELS AB We have previously demonstrated that parathyroid hormone 2 (PTH2) receptors are expressed in dorsal root ganglion (DRG) neurons and that its endogenous agonist tuberoinfundibular peptide of 39 residues (TIP39) causes nociceptive paw flexor responses after intraplantar administration. Here we found that the PTH2 receptor is selectively localized on myelinated A-, but not unmyelinated C-fibers using immunohistochemical labeling, based on PTH2 receptor expression on antibody N52-positive medium/large-sized DRG neurons, but not on TRPV1, substance P, P2X(3) receptor or isolectin B4-binding protein-positive small-sized DRG neurons. Pharmacological studies showed that TIP39-induced nociceptive responses were mediated by activation of G(s) and cAMP-dependent protein kinase. We also found that nociceptive responses induced by TIP39- or the cAMP analog 8-bromo-cAMP were significantly greater following partial sciatic nerve injury induced neuropathic pain, without changes in PTH2 receptor expression. Together these data suggest that activation of PTH2 receptors stimulates nociceptive A-fiber through G(s)-cAMP-dependent protein kinase signaling, and this pathway has elevated sensitization following nerve injury. C1 [Matsumoto, Misaki; Kondo, Saori; Ueda, Hiroshi] Nagasaki Univ, Grad Sch Biomed Sci, Div Mol Pharmacol & Neurosci, Nagasaki 8528521, Japan. [Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA. RP Ueda, H (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Div Mol Pharmacol & Neurosci, 1-14 Bunkyo Machi, Nagasaki 8528521, Japan. EM ueda@nagasaki-u.ac.jp FU MEXT [17109015, 21600007]; Ministry of Health, Labor and Welfare of Japan [398-49]; National Institute of Mental Health, NIH, USA FX We thank Makoto Inoue for his kind discussion on experimental design. The resear5ch described in this article was supported by MEXT KAKENHI-S to H.U. (17109015) and MEXT KAKENHI-C to M.M. (21600007), and Health Labour Sciences Research Grant ``Third Term Comprehensive Control Research for Cancer'' (398-49) from the Ministry of Health, Labor and Welfare of Japan to H.U. T. U. was supported by the Intramural Program of the National Institute of Mental Health, NIH, USA. NR 48 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2010 VL 112 IS 2 BP 521 EP 530 DI 10.1111/j.1471-4159.2009.06473.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 535UH UT WOS:000272996600019 PM 19891737 ER PT J AU Xi, ZX Li, X Peng, XQ Li, J Chun, L Gardner, EL Thomas, AG Slusher, BS Ashby, CR AF Xi, Zheng-Xiong Li, Xia Peng, Xiao-Qing Li, Jie Chun, Lauren Gardner, Eliot L. Thomas, Ajit G. Slusher, Barbara S. Ashby, Charles R., Jr. TI Inhibition of NAALADase by 2-PMPA attenuates cocaine-induced relapse in rats: a NAAG-mGluR2/3-mediated mechanism SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 2-(phosphonomethyl)pentanedioic acid; cocaine; dopamine; glutamate; N-acetyl-aspartatylglutamate; relapse ID METABOTROPIC GLUTAMATE-RECEPTOR; CENTRAL AMYGDALA INJECTIONS; AGONIST LY379268 ATTENUATE; LINKED-ACIDIC DIPEPTIDASE; DRUG-SEEKING BEHAVIOR; NUCLEUS-ACCUMBENS; N-ACETYLASPARTYLGLUTAMATE; INDUCED REINSTATEMENT; ANTIPSYCHOTIC ACTIVITY; NAAG AB Pharmacological activation of group II metabotropic glutamate receptors (mGluR2/3) inhibits cocaine self-administration and reinstatement of drug-seeking behavior, suggesting a possible use of mGluR2/3 agonists in the treatment of cocaine dependence. In this study, we investigated whether elevation of the endogenous mGluR2/3 ligand N-acetyl-aspartatylglutamate (NAAG) levels by the N-acetylated-alpha-linked-acidic dipeptidase inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) attenuates cocaine self-administration and cocaine-induced reinstatement of drug seeking. N-acetylated-alpha-linked-acidic dipeptidase is a NAAG degradation enzyme that hydrolyzes NAAG to N-acetylaspartate and glutamate. Systemic administration of 2-PMPA (10-100 mg/kg, i.p.) inhibited intravenous self-administration maintained by low unit doses of cocaine and cocaine (but not sucrose)-induced reinstatement of drug-seeking behavior. Microinjections of 2-PMPA (3-5 mu g/side) or NAAG (3-5 mu g/side) into the nucleus accumbens (NAc), but not into the dorsal striatum, also inhibited cocaine-induced reinstatement, an effect that was blocked by intra-NAc injection of LY341495, a selective mGluR2/3 antagonist. In vivo microdialysis demonstrated that 2-PMPA (10-100 mg/kg, i.p.) produced a dose-dependent reduction in both extracellular dopamine (DA) and glutamate, an effect that was also blocked by LY341495. Finally, pre-treatment with 2-PMPA partially attenuated cocaine-enhanced extracellular NAc DA, while completely blocking cocaine-enhanced extracellular NAc glutamate in rats during reinstatement testing. Intra-NAc perfusion of LY341495 blocked 2-PMPA-induced reductions in cocaine-enhanced extracellular NAc glutamate, but not DA. These findings suggest that 2-PMPA is effective in attenuating cocaine-induced reinstatement of drug-seeking behavior, likely by attenuating cocaine-induced increases in NAc DA and glutamate via pre-synaptic mGluR2/3s. C1 [Xi, Zheng-Xiong; Li, Xia; Peng, Xiao-Qing; Li, Jie; Chun, Lauren; Gardner, Eliot L.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. [Thomas, Ajit G.; Slusher, Barbara S.] Guilford Pharmaceut Inc, Dept Res, Baltimore, MD 21224 USA. [Ashby, Charles R., Jr.] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA. RP Xi, ZX (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov OI PENG, XIAOQING/0000-0002-7272-5428 FU National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services. NR 49 TC 30 Z9 31 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2010 VL 112 IS 2 BP 564 EP 576 DI 10.1111/j.1471-4159.2009.06478.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 535UH UT WOS:000272996600023 PM 19895667 ER PT J AU Ong, RC Stopfer, M AF Ong, Rose C. Stopfer, Mark TI Olfactory Coding: Unusual Conductances Contribute to Sparse Neural Representation. Focus on "Intrinsic Membrane Properties and Inhibitory Synaptic Input of Kenyon Cells as Mechanisms for Sparse Coding?" SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PRIMARY VISUAL-CORTEX; MUSHROOM BODY; STIMULI; NEURONS; MEMORY; SYSTEM; BRAIN C1 [Ong, Rose C.; Stopfer, Mark] NICHHD, NIH, Bethesda, MD 20892 USA. [Ong, Rose C.] Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China. RP Stopfer, M (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM stopferm@mail.nih.gov NR 28 TC 0 Z9 0 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2010 VL 103 IS 1 BP 2 EP 3 DI 10.1152/jn.00330.2009 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 542VD UT WOS:000273526000002 PM 19906885 ER PT J AU Yee, LTS Roe, K Courtney, SM AF Yee, Lydia T. S. Roe, Katherine Courtney, Susan M. TI Selective Involvement of Superior Frontal Cortex During Working Memory for Shapes SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; PREFRONTAL CORTEX; INFEROTEMPORAL CORTEX; PARIETAL CORTEX; NEURAL SYSTEM; OBJECT SHAPE; VISUAL SHAPE; REPRESENTATION; MAINTENANCE; NEURONS AB Yee LTS, Roe K, Courtney SM. Selective involvement of superior frontal cortex during working memory for shapes. J Neurophysiol 103: 557-563, 2010. First published November 18, 2009; doi: 10.1152/jn.91299.2008. A spatial/nonspatial functional dissociation between the dorsal and ventral visual pathways is well established and has formed the basis of domain-specific theories of prefrontal cortex (PFC). Inconsistencies in the literature regarding prefrontal organization, however, have led to questions regarding whether the nature of the dissociations observed in PFC during working memory are equivalent to those observed in the visual pathways for perception. In particular, the dissociation between dorsal and ventral PFC during working memory for locations versus object identities has been clearly present in some studies but not in others, seemingly in part due to the type of objects used. The current study compared functional MRI activation during delayed-recognition tasks for shape or color, two object features considered to be processed by the ventral pathway for perceptual recognition. Activation for the shape-delayed recognition task was greater than that for the color task in the lateral occipital cortex, in agreement with studies of visual perception. Greater memory-delay activity was also observed, however, in the parietal and superior frontal cortices for the shape than for the color task. Activity in superior frontal cortex was associated with better performance on the shape task. Conversely, greater delay activity for color than for shape was observed in the left anterior insula and this activity was associated with better performance on the color task. These results suggest that superior frontal cortex contributes to performance on tasks requiring working memory for object identities, but it represents different information about those objects than does the ventral frontal cortex. C1 [Yee, Lydia T. S.; Roe, Katherine; Courtney, Susan M.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA. [Courtney, Susan M.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21218 USA. [Courtney, Susan M.] Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA. [Roe, Katherine] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Yee, Lydia T. S.] Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. RP Courtney, SM (reprint author), Johns Hopkins Univ, Dept Psychol & Brain Sci, 204 Ames Hall,3400 N Charles St, Baltimore, MD 21218 USA. EM courtney@jhu.edu FU National Institute of Mental Health [R01 MH-061625] FX This work was funded in part by National Institute of Mental Health Grant R01 MH-061625 to S. M. Courtney. NR 44 TC 17 Z9 17 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2010 VL 103 IS 1 BP 557 EP 563 DI 10.1152/jn.91299.2008 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 542VD UT WOS:000273526000052 PM 19923241 ER PT J AU Woronowicz, A Cawley, NX Chang, SY Koshimizu, H Phillips, AW Xiong, ZG Loh, YP AF Woronowicz, Alicja Cawley, Niamh X. Chang, Su-Youne Koshimizu, Hisatsugu Phillips, Andre W. Xiong, Zhi-Gang Loh, Y. Peng TI Carboxypeptidase E Knockout Mice Exhibit Abnormal Dendritic Arborization and Spine Morphology in Central Nervous System Neurons SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE carboxypeptidase E; dendritic pruning; hippocampus; BDNF ID CA1 PYRAMIDAL CELLS; SPATIAL MEMORY; IN-VIVO; HIPPOCAMPAL-NEURONS; NMDA RECEPTOR; GROWTH; BDNF; AXON; COMPLEXITY; PLASTICITY AB Carboxypeptidase E (CPE) is involved in maturation of neuropeptides and sorting of brain-derived neurotrophic factor (BDNF) to the regulated pathway for activity-dependent secretion from CNS neurons. CPE knockout (CPE-KO) mice have many neurological deficits, including deficits in learning and memory. Here, we analyzed the dendritic arborization and spine morphology of CPE-KO mice to determine a possible correlation of defects in such structures with the neurological deficits observed in these animals. Analysis of pyramidal neurons in layer V of cerebral cortex and in hippocampal CA1 region in 14-week-old CPE-KO mice showed more dendritic complexity compared with wild type (WT) mice. There were more dendritic intersections and more branch points in CPE-KO vs. WT neurons. Comparison of pyramidal cortical neurons in 6- vs. 14-week-old WT mice showed a decrease in dendritic arborization, reflecting the occurrence of normal dendritic pruning. However, this did not occur in CPE-KO neurons. Furthermore, analysis of spine morphology demonstrated a significant increase in the number of D-type spines regarded as nonfunctional in the cortical neurons of CPE-KO animals. Our findings suggest that CPE is an important, novel player in mediating appropriate dendritic patterning and spine formation in CNS neurons. (C) 2009 Wiley-Liss, Inc. C1 [Woronowicz, Alicja; Cawley, Niamh X.; Koshimizu, Hisatsugu; Phillips, Andre W.; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, Bethesda, MD USA. [Chang, Su-Youne; Xiong, Zhi-Gang] Robert S Dow Neurobiol Labs, Portland, OR USA. RP Loh, YP (reprint author), NICHD, Cellular Neurobiol Sect, NIH, 49 Convent Dr,Bldg 49,Rm 5A-22, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov RI Koshimizu, Hisatsugu/G-5536-2010 FU NIH [RO1NS049470]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Contract grant sponsor: NIH; Contract grant number: RO1NS049470 (to Z.-G.X.); Contract grant sponsor: Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 57 TC 13 Z9 13 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN PY 2010 VL 88 IS 1 BP 64 EP 72 DI 10.1002/jnr.22174 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 526UQ UT WOS:000272320500007 PM 19598241 ER PT J AU Xiong, Y Mahmood, A Qu, CS Kazmi, H Zhang, ZG Noguchi, CT Schallert, T Chopp, M AF Xiong, Ye Mahmood, Asim Qu, Changsheng Kazmi, Humaira Zhang, Zheng Gang Noguchi, Constance T. Schallert, Timothy Chopp, Michael TI Erythropoietin Improves Histological and Functional Outcomes after Traumatic Brain Injury in Mice in the Absence of the Neural Erythropoietin Receptor SO JOURNAL OF NEUROTRAUMA LA English DT Article DE erythropoietin receptor null; mouse; sensorimotor; spatial learning; traumatic brain injury ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; FOCAL CEREBRAL-ISCHEMIA; IN-VITRO; ENHANCES NEUROGENESIS; NEONATAL STROKE; SPATIAL MEMORY; UP-REGULATION; HEAD-INJURY; RATS; PROTECTS AB Erythropoietin (EPO), essential for erythropoiesis, provides neuroprotection. The EPO receptor (EPOR) is expressed in both neural and non-neural cells in the brain. This study was designed to test the hypothesis that EPO provides beneficial therapeutic effects, even in the absence of the neural EPOR. In this study, EPOR-null mice were rescued with selective EpoR expression driven by the endogenous EpoR promoter in hematopoietic tissue, but not in the neural cells. Anesthetized young adult female EPOR-null and wild-type mice were subjected to traumatic brain injury (TBI) induced by controlled cortical impact. EPO (5000 U/kg) or saline was intraperitoneally administered at 6 h and 3 and 7 days post-injury. Sensorimotor and spatial learning functions were assessed. Expression of EPOR and its downstream signal proteins were evaluated by Western blot analysis. Our data demonstrated that EPO treatment significantly reduced cortical tissue damage and hippocampal cell loss, and improved spatial learning following TBI in both the wild-type and EPOR-null mice. EPO treatment significantly improved sensorimotor functional recovery, with better outcomes in the wild-type mice. EPO treatment upregulated anti-apoptotic proteins (p-Akt and Bcl-XL) in the ipsilateral hippocampus and cortex of the injured wild-type and EPOR-null mice. These data demonstrate that EPO significantly provides neuroprotection following TBI, even in the absence of EPOR in the neural cells, suggesting that its therapeutic benefits may be mediated through vascular protection. C1 [Zhang, Zheng Gang; Chopp, Michael] Henry Ford Hlth Syst, Dept Neurol, Detroit, MI 48202 USA. [Xiong, Ye; Mahmood, Asim; Qu, Changsheng; Kazmi, Humaira] Henry Ford Hlth Syst, Dept Neurosurg, Detroit, MI 48202 USA. [Noguchi, Constance T.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Schallert, Timothy] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Schallert, Timothy] Univ Texas Austin, Inst Neurosci, Austin, TX 78712 USA. [Chopp, Michael] Oakland Univ, Dept Phys, Rochester, MI USA. RP Chopp, M (reprint author), Henry Ford Hlth Syst, Dept Neurol, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM chopp@neuro.hfh.edu OI Xiong, Ye/0000-0001-9770-6031 FU National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Health [RO1 NS62002, PO1 NS42345] FX This work was supported by National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Health grants RO1 NS62002 and PO1 NS42345, and NIDDK Intramural Research. NR 51 TC 39 Z9 41 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JAN PY 2010 VL 27 IS 1 BP 205 EP 215 DI 10.1089/neu.2009.1001 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 548RF UT WOS:000273983200018 PM 19715391 ER PT J AU Vexler, A Liu, AY Schisterman, E AF Vexler, Albert Liu, Aiyi Schisterman, Enrique TI Nonparametric deconvolution of density estimation based on observed sums SO JOURNAL OF NONPARAMETRIC STATISTICS LA English DT Article DE deconvolution; design of experiments; Fourier inversion; nonparametric density estimation; pooling blood samples ID ROC CURVE ANALYSIS; ESTIMATING PREVALENCE; POOLED ASSESSMENTS; BIOMARKERS; DISTRIBUTIONS; BIOSPECIMENS; EFFICIENCY; ACCURACY; SUBJECT; DISEASE AB This paper develops a methodology for distribution-free estimation of a density function based on observed sums or pooled data. The proposed methods employ a Fourier approach to nonparametric deconvolution of a density estimate. Asymptotic normality is established and an upper bound for the integrated absolute error is given for the proposed density estimator. Monte Carlo simulations are used to examine the performance of the density estimators. The proposed techniques are exemplified using data from a study of biomarkers associated with coronary heart disease. C1 [Vexler, Albert] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA. [Liu, Aiyi; Schisterman, Enrique] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Bethesda, MD 20892 USA. RP Vexler, A (reprint author), SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA. EM avexler@buffalo.edu OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 34 TC 2 Z9 2 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1048-5252 EI 1029-0311 J9 J NONPARAMETR STAT JI J. Nonparametr. Stat. PY 2010 VL 22 IS 1 BP 23 EP 39 DI 10.1080/10485250903094286 PG 17 WC Statistics & Probability SC Mathematics GA 567WN UT WOS:000275478700002 ER PT J AU Wu, CO Tian, X Yu, J AF Wu, Colin O. Tian, Xin Yu, Jarvis TI Nonparametric estimation for time-varying transformation models with longitudinal data SO JOURNAL OF NONPARAMETRIC STATISTICS LA English DT Article DE linear transformation models; local polynomials; longitudinal samples; time-varying coefficients; two-step estimation ID COEFFICIENT MODELS; CONDITIONAL DISTRIBUTION; CARDIOVASCULAR-DISEASE; CROSS-VALIDATION; LINEAR-MODELS; RISK-FACTORS; REGRESSION; KERNEL; INFERENCE; CURVES AB Regression methods for longitudinal analyses have traditionally focused on conditional-mean-based models. In many situations, the relevant scientific questions could be better studied by modelling the conditional distributions of the outcome variables as a function of time and other covariates. In this paper, we propose a class of time-varying transformation models for modelling the cumulative distribution function of a response variable conditioning on a set of covariates, and develop a two-step smoothing method for estimating the time-varying parameters. Applications and finite sample properties of our models and smoothing estimators are demonstrated through a cohort study of childhood obesity and cardiovascular risk factors, and a simulation study. Theoretical properties are developed for the two-step local polynomial estimators. Our approach provides a useful statistical tool in longitudinal analysis when the conditional-mean-based methods are inappropriate. C1 [Wu, Colin O.; Tian, Xin; Yu, Jarvis] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Wu, CO (reprint author), NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. EM wuc@nhlbi.nih.gov NR 34 TC 5 Z9 5 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1048-5252 EI 1029-0311 J9 J NONPARAMETR STAT JI J. Nonparametr. Stat. PY 2010 VL 22 IS 2 BP 133 EP 147 DI 10.1080/10485250903160988 PG 15 WC Statistics & Probability SC Mathematics GA 567WP UT WOS:000275478900001 ER PT J AU Liu, YJ Abendschein, D Woodard, GE Rossin, R McCommis, K Zheng, J Welch, MJ Woodard, PK AF Liu, Yongjian Abendschein, Dana Woodard, Geoffrey E. Rossin, Raffaella McCommis, Kyle Zheng, Jie Welch, Michael J. Woodard, Pamela K. TI Molecular Imaging of Atherosclerotic Plaque with Cu-64-Labeled Natriuretic Peptide and PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE atherosclerosis; PET; natriuretic peptide; vascular targeting ID VULNERABLE PLAQUE; POTENTIAL AGENT; EXPRESSION; ENDOTHELIUM; PROGRESSION; RECEPTORS; MICROPET; RABBITS; LESIONS; SYSTEM AB Cardiovascular disease is the leading cause of death worldwide. PET has the potential to provide information on the biology and metabolism of atherosclerotic plaques. Natriuretic peptides (NPs) have potent antiproliferative and antimigratory effects on vascular smooth-muscle cells (VSMCs) and, in atherosclerosis, participate in vascular remodeling, in which the expression of NP clearance receptors (NPR-Cs) is upregulated both in endothelium and in VSMCs. Methods: We investigated the potential of a C-type atrial natriuretic factor (C-ANF) to image developing plaque-like lesions in vivo. C-ANF was functionalized with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid ( DOTA) and labeled with Cu-64 for noninvasive PET in a hypercholesterolemic rabbit with atherosclerotic-like lesions induced by air desiccation of a femoral artery, followed by balloon overstretch of the developing neointima. Histopathology and immunohistochemistry were performed to assess plaque development and NPR-C localization. Results: Cu-64-DOTA-C-ANF uptake in the atherosclerotic region was visible on small-animal PET images, with the highest target-to-background ratio (3.59 +/- 0.94) observed after the air desiccation-induced injury. Immunohistochemistry and immunofluorescence staining showed NPR-C near the luminal surface of the plaque and in VSMCs. PET and immunohistochemistry competitive blocking studies confirmed receptor-mediated tracer uptake in the plaque. With blocking, PET tracer localization of atherosclerotic to control arteries was decreased from 1.42 +/- 0.02 to 1.06 +/- 0.06 (P < 0.001). Conclusion: We demonstrated that Cu-64-DOTA-C-ANF is a promising candidate tracer for in vivo PET of NPR-Cs on atherosclerotic plaques. C1 [Liu, Yongjian; Rossin, Raffaella; McCommis, Kyle; Zheng, Jie; Welch, Michael J.; Woodard, Pamela K.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Abendschein, Dana] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. [Woodard, Geoffrey E.] NIAID, Bethesda, MD 20892 USA. RP Woodard, PK (reprint author), Washington Univ, Sch Med, Dept Radiol, 510 S Kingshighway Blvd,Campus Box 8131, St Louis, MO 63110 USA. EM woodardp@mir.wustl.edu RI Woodard, Geoffrey/A-8608-2009 FU National Institutes of Health as a Program of Excellence in Nanotechnology [HL080729]; National Cancer Institute [CA86307] FX We thank Terry Sharp, Paul Eisenbies, Nicole Fettig, Margaret Morris, Amanda Roth, Lori Strong, Ann Stroncek, Jerrel Rutlin, and James Kozlowski for their assistance with the imaging studies; Susie Grathwohl for technical help with animal surgery and postoperative monitoring; and Tom Voller and Curtis Carey for 64Cu production. This material is based on work supported by the National Institutes of Health as a Program of Excellence in Nanotechnology (HL080729). The production of 64Cu is supported by the National Cancer Institute (CA86307). NR 31 TC 25 Z9 26 U1 1 U2 9 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2010 VL 51 IS 1 BP 85 EP 91 DI 10.2967/jnumed.109.066977 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 539OG UT WOS:000273263800017 PM 20008978 ER PT J AU Terry, GE Hirvonen, J Liow, JS Zoghbi, SS Gladding, R Tauscher, JT Schaus, JM Phebus, L Felder, CC Morse, CL Donohue, SR Pike, VW Halldin, C Innis, RB AF Terry, Garth E. Hirvonen, Jussi Liow, Jeih-San Zoghbi, Sami S. Gladding, Robert Tauscher, Johannes T. Schaus, John M. Phebus, Lee Felder, Christian C. Morse, Cheryl L. Donohue, Sean R. Pike, Victor W. Halldin, Christer Innis, Robert B. TI Imaging and Quantitation of Cannabinoid CB1 Receptors in Human and Monkey Brains Using F-18-Labeled Inverse Agonist Radioligands SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE positron emission tomography; brain imaging neuroimaging ID POSITRON-EMISSION-TOMOGRAPHY; PET; TRANSPORTER; MODEL AB We recently demonstrated that C-11-MePPEP, a PET ligand for CB1 receptors, has such high uptake in the human brain that it can be imaged for 210 min and that receptor density can be quantified as distribution volume (V-T) using the gold standard of compartmental modeling. However, C-11-MePPEP had relatively poor retest and intersubject variabilities, which were likely caused by errors in the measurements of radioligand in plasma at low concentrations by 120 min. We sought to find an analog of C-11-MePPEP that would provide more accurate plasma measurements. We evaluated several promising analogs in the monkey brain and chose the F-18-di-deutero fluoromethoxy analog (F-18-FMPEP-d(2)) to evaluate further in the human brain. Methods: C-11-FMePPEP, F-18-FEPEP, F-18-FMPEP, and F-18-FMPEP-d(2) were studied in 5 monkeys with 10 PET scans. We calculated VT using compartmental modeling with serial measurements of unchanged parent radioligand in arterial plasma and radioactivity in the brain. Nonspecific binding was determined by administering a receptor-saturating dose of rimonabant, an inverse agonist at the CB1 receptor. Nine healthy human subjects participated in 17 PET scans using F-18-FMPEP-d(2), with 8 subjects having 2 PET scans to assess retest variability. To identify sources of error, we compared intersubject and retest variability of brain uptake, arterial plasma measurements, and VT. Results: F-18-FMPEP-d(2) had high uptake in the monkey brain, with greater than 80% specific binding, and yielded less radioactivity uptake in bone than did F-18-FMPEP. High brain uptake with F-18-FMPEP-d(2) was also observed in humans, in whom VT was well identified within approximately 60 min. Retest variability of plasma measurements was good (16%); consequently, VT had a good retest variability (14%), intersubject variability (26%), and intraclass correlation coefficient (0.89). VT increased after 120 min, suggesting an accumulation of radiometabolites in the brain. Radioactivity accumulated in the skull throughout the entire scan but was thought to be an insignificant source of data contamination. Conclusion: Studies in monkeys facilitated our development and selection of F-18-FMPEP-d(2), compared with F-18-FMPEP, as a radioligand demonstrating high brain uptake, high percentage of specific binding, and reduced uptake in bone. Retest analysis in human subjects showed that F-18-FMPEP-d(2) has greater precision and accuracy than C-11-MePPEP, allowing smaller sample sizes to detect a significant difference between groups. C1 [Terry, Garth E.; Hirvonen, Jussi; Liow, Jeih-San; Zoghbi, Sami S.; Gladding, Robert; Morse, Cheryl L.; Donohue, Sean R.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Terry, Garth E.; Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. [Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C.] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, Bldg 31,Room B2B37,31 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI Tauscher, Johannes/M-5976-2016 FU Cooperative Research and Development Agreement with Eli Lilly; Intramural Program of NIMH [Z01-MH-002852-04, Z01-MH002793-06]; Academy of Finland; Finnish Cultural Foundation; Finnish Foundation for Alcohol Studies; Finnish Medical Foundation; Instrumentarium Foundation; Jalmari and Rauha Ahokas Foundation; Paulo Foundation; Research Foundation of Orion Corporation; Yrjo Jahnsson Foundation FX We thank Pavitra Kannan, Kimberly Jenko, and Kacey Anderson for measurements of radioligand in plasma; Yi Zhang for preparation of 18F-FMPEP-d2; Maria D. Ferraris Araneta, William C. Kreisl, and Barbara Scepura for subject recruitment and care; the NIH PET Department for imaging; and PMOD Technologies for providing its image analysis and modeling software. This research was supported by a Cooperative Research and Development Agreement with Eli Lilly; by the Intramural Program of NIMH ( projects Z01-MH-002852-04 and Z01-MH002793-06); and grants from the Academy of Finland, the Finnish Cultural Foundation, the Finnish Foundation for Alcohol Studies, the Finnish Medical Foundation, the Instrumentarium Foundation, the Jalmari and Rauha Ahokas Foundation, the Paulo Foundation, the Research Foundation of Orion Corporation, and the Yrjo Jahnsson Foundation. NR 19 TC 39 Z9 39 U1 2 U2 12 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2010 VL 51 IS 1 BP 112 EP 120 DI 10.2967/jnumed.109.067074 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 539OG UT WOS:000273263800021 PM 20008988 ER PT J AU Fujimura, Y Kimura, Y Simeon, FG Dickstein, LP Pike, VW Innis, RB Fujita, M AF Fujimura, Yota Kimura, Yasuyuki Simeon, Fabrice G. Dickstein, Leah P. Pike, Victor W. Innis, Robert B. Fujita, Masahiro TI Biodistribution and Radiation Dosimetry in Humans of a New PET Ligand, F-18-PBR06, to Image Translocator Protein (18 kDa) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE MIRD scheme; defluorination; inflammation; microglia; aryloxyanilide ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; NONHUMAN-PRIMATES; BRAIN; RADIOLIGAND AB As a PET biomarker for inflammation, translocator protein (18 kDa) (TSPO) can be measured with an F-18-labeled aryloxyanilide, F-18-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline (F-18-PBR06), in the human brain. The objective of this study was to estimate the radiation absorbed doses of F-18-PBR06 based on biodistribution data in humans. Methods: After the injection of F-18-PBR06, images were acquired from head to thigh in 7 healthy humans. Urine was collected at various time points. Radiation absorbed doses were estimated by the MIRD scheme. Results: Moderate to high levels of radioactivity were observed in organs with high densities of TSPO and in organs of metabolism and excretion. Bone had low levels of radioactivity. The effective dose was 18.5 mu Sv/MBq. Conclusion: The effective dose of F-18-PBR06, compared with other F-18 radioligands, was moderate. This radioligand had negligible defluorination, as indirectly assessed by bone radioactivity. Doses to the gallbladder wall and spleen may limit the amount of permissible injected radioactivity. C1 [Fujimura, Yota; Kimura, Yasuyuki; Simeon, Fabrice G.; Dickstein, Leah P.; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 31,Room B2B37,31 Ctr Dr,MSC-2035, Bethesda, MD 20892 USA. EM fujitam@mail.nih.gov RI Kimura, Yasuyuki/D-4459-2016; OI Kimura, Yasuyuki/0000-0002-7927-9483; Dickstein, Leah/0000-0002-4779-4122 FU Intramural Program of the NIMH-NIH [Z01-MH002852-04]; JSPS Research Fellowship in Biomedical and Behavioral Research at NIH FX We thank Maria D. Ferraris Araneta, Barbara A. Scepura, and Gerald L. Hodges for screening and care of the subjects; the staff of the PET Department for successful completion of PET scans; the staff of the Clinical Center for 18F production; Jeih-San Liow and Robert L. Gladding for assisting with data processing; and PMOD Technologies ( Zurich, Switzerland) for providing its image-analysis and modeling software. This research was supported by the Intramural Program of the NIMH-NIH (project Z01-MH002852-04) and by a JSPS Research Fellowship in Biomedical and Behavioral Research at NIH. NR 18 TC 18 Z9 18 U1 1 U2 7 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2010 VL 51 IS 1 BP 145 EP 149 DI 10.2967/jnumed.109.068064 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 539OG UT WOS:000273263800025 PM 20008980 ER PT J AU Ersig, AL Ayres, L Hadley, DW Koehly, LM AF Ersig, Anne L. Ayres, Lioness Hadley, Donald W. Koehly, Laura M. TI Explanations of Risk in Families Without Identified Mutations for Hereditary Nonpolyposis Colorectal Cancer SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE within- and across-case method; hereditary non-polyposis colorectal cancer; HNPCC; genetic testing; explanations and interpretations of risk ID LYNCH-SYNDROME; OVARIAN-CANCER; RECOMMENDATIONS; INDIVIDUALS; PERCEPTIONS; INFORMATION; STRATEGIES; HEALTH; BREAST; WOMEN AB Purpose: Genetic testing for hereditary forms of cancer does not always identify a causative mutation. Little is known about personal or family response to these indeterminate results when a hereditary form of cancer is suspected. This study explored thoughts about and responses to risk for hereditary nonpolyposis colorectal cancer (HNPCC) when a family member has received indeterminate genetic test results. Design: In this qualitative study, data were gathered from index cases who received indeterminate genetic test results through a longitudinal study offering genetic counseling and testing for HNPCC. First-degree relatives of these indeterminate index cases were also invited to participate in the qualitative interview. Methods: Semistructured telephone interviews were conducted with index cases and their at-risk first-degree relatives. Data were analyzed using the within- and across-case method. Findings: The across-case analysis led to the development of the Awareness and Surveillance Trajectory, which describes individual interpretations of and responses to risk, based on personal and family history. Explanations of risk addressed the meaning of cancer in the family and provided context for individual interpretations. They were identified using within-case analysis and organized into a typology: innate, exceptional, idiosyncratic, and undeveloped explanations. Conclusions: Members of families without identified HNPCC mutations vary in their explanations for, interpretations of, and responses to indeterminate genetic test results. Clinical Relevance: Explanations of family risk and interpretations of individual risk offer healthcare providers valuable information. In combination with the Awareness and Surveillance Trajectory, assessment of these beliefs can facilitate development of individualized recommendations and strategies for possible preventive actions. C1 [Ersig, Anne L.; Ayres, Lioness] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Ersig, Anne L.; Hadley, Donald W.; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Ersig, AL (reprint author), Room 305 NB,50 Newton Rd, Iowa City, IA 52242 USA. EM anne-ersig@uiowa.edu FU National Human Genome Research Institute [Z01HG200335-01]; National Institute of Nursing Research, National Institutes of Health FX We thank the families who participated, without whom this research would not be possible. We also thank Janet K. Williams, RN, PhD, FAAN, and the three anonymous reviewers for their thoughtful comments on drafts of this paper. This research was supported by the Intramural Research Programs of the National Human Genome Research Institute (Z01HG200335-01, Laura Koehly, PI) at the National Institutes of Health, Bethesda, Maryland. Data presented in this manuscript were collected through a protocol monitored by the Institutional Review Board at the National Human Genome Research Institute (Protocol #95-HG-0165; Donald Hadley, PI). Dr. Ersig was supported by a Graduate Partnerships Program fellowship from the National Institute of Nursing Research, National Institutes of Health. NR 25 TC 3 Z9 3 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2010 VL 42 IS 2 BP 139 EP 146 DI 10.1111/j.1547-5069.2010.01342.x PG 8 WC Nursing SC Nursing GA 604WW UT WOS:000278310200005 PM 20618598 ER PT J AU Greco, KE Nail, LM Kendall, J Cartwright, J Messecar, DC AF Greco, Karen E. Nail, Lillian M. Kendall, Judy Cartwright, Juliana Messecar, Deborah C. TI Mammography Decision Making in Older Women With a Breast Cancer Family History SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE Mammography; decision making; breast cancer screening; breast screening; breast cancer; family history; grounded theory; qualitative research ID AVERAGE-RISK WOMEN; SCREENING MAMMOGRAPHY; RECENT DECLINE; BELIEFS; SAMPLE; WORRY; RATES AB Purpose: This study's purpose is to describe and explain how women 55 years of age and older with a family history of breast cancer make screening mammography decisions. Design: A qualitative design based on grounded theory. This purposeful sample consisted of 23 women 55 years of age or older with one more first-degree relatives diagnosed with breast cancer. Method: Open-ended interviews were conducted with 23 women 55 years of age and older with a family history of breast cancer using a semistructured interview guide. Transcribed interview data were analyzed using constant comparative analysis to identify the conditions, actions, and consequences associated with participant's screening mammography decision making. Findings: Women reported becoming aware of their breast cancer risk usually due to a triggering event such as having a family member diagnosed with breast cancer, resulting in women "guarding against cancer." Women's actions included having mammograms, getting health check-ups, having healthy behaviors, and being optimistic. Most women reported extraordinary faith in mammography, often ignoring negative mammogram information. A negative mammogram gave women peace of mind and assurance that breast cancer was not present. Being called back for additional mammograms caused worry, especially with delayed results. Conclusions: The "guarding against cancer" theory needs to be tested in other at-risk populations and ultimately used to test strategies that promote cancer screening decision making and the adoption of screening behaviors in those at increased risk for developing cancer. Clinical Relevance: Women 55 years of age and older with a breast cancer family history need timely mammogram results, mammography reminders, and psychosocial support when undergoing a mammography recall or other follow-up tests. C1 [Greco, Karen E.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Kendall, Judy] Oregon Hlth & Sci Univ, Sch Nursing, Div Child & Family Nursing, Portland, OR 97201 USA. RP Greco, KE (reprint author), 8901 Wisconsin Ave,Bldg 8,Room 5105, Bethesda, MD 20889 USA. EM karen.greco@nih.gov FU John A. Hartford Foundation; National Institutes of Health [T32 NR0007048, T32 NR7048-15]; Oregon Health & Science University; Oncology Nursing Foundation FX The primary author would like to acknowledge support from the following funding sources: John A. Hartford Foundation's Building Academic Geriatric Nursing Capacity 2002-2004 Pre-Doctoral Scholarship; National Institutes of Health National Research Service Award for Research Training: Nursing Care For Older Populations (T32 NR0007048); National Institutes of Health National Research Service Award for Research Training: Nursing Care For Older Populations (T32 NR7048-15); Oregon Health & Science University Dean's Scholarship; and Oncology Nursing Foundation 2002 Doctoral Scholarship. The authors would also like to acknowledge Richard J. Greco for his assistance with the "guarding against cancer" diagram in the Figure. NR 26 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2010 VL 42 IS 3 BP 348 EP 356 DI 10.1111/j.1547-5069.2010.01335.x PG 9 WC Nursing SC Nursing GA 643HA UT WOS:000281285000015 PM 20738746 ER PT J AU Ross, SA AF Ross, Sharon A. TI Interactions Between Diet and Epigenetics: Implications for Cancer Prevention SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Ross, Sharon A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2010 VL 3 IS 2-3 BP 62 EP 62 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 678ZP UT WOS:000284126800018 ER PT J AU Milner, JA AF Milner, J. A. TI Emerging Topics in Nutrigenomics and Cancer Prevention SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Milner, J. A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2010 VL 3 IS 2-3 BP 67 EP 67 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 678ZP UT WOS:000284126800031 ER PT J AU Ferrucci, LM Cross, AJ Gunter, MJ Ahn, J Mayne, ST Ma, XM Chanock, SJ Yeager, M Graubard, BI Berndt, SI Huang, WY Hayes, RB Sinha, R AF Ferrucci, Leah M. Cross, Amanda J. Gunter, Marc J. Ahn, Jiyoung Mayne, Susan T. Ma, Xiaomei Chanock, Stephen J. Yeager, Meredith Graubard, Barry I. Berndt, Sonja I. Huang, Wen-Yi Hayes, Richard B. Sinha, Rashmi TI Xenobiotic Metabolizing Genes, Meat-Related Exposures, and Risk of Advanced Colorectal Adenoma SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; EPOXIDE HYDROLASE POLYMORPHISMS; N-NITROSO COMPOUNDS; CANCER SCREENING TRIAL; RED MEAT; CIGARETTE-SMOKING; ACETYLTRANSFERASE GENES; ENZYME POLYMORPHISMS; HETEROCYCLIC AMINES; CYP2A6 ACTIVITY C1 [Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ferrucci, Leah M.; Mayne, Susan T.; Ma, Xiaomei] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Gunter, Marc J.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Ahn, Jiyoung; Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, Div Epidemiol, New York, NY 10016 USA. RP Sinha, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM sinhar@mail.nih.gov RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Hayes, Richard/0000-0002-0918-661X FU National Institutes of Health, National Cancer Institute; National Cancer Institute [TU2 CA105666]; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, by grant TU2 CA105666 from the National Cancer Institute, and by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 65 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2010 VL 3 IS 4-6 BP 170 EP 181 DI 10.1159/000324351 PG 12 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 751LA UT WOS:000289617900005 PM 21474949 ER PT J AU Starlard-Davenport, A Tryndyak, V Kosyk, O Ross, SR Rusyn, I Beland, FA Pogribny, IP AF Starlard-Davenport, Athena Tryndyak, Volodymyr Kosyk, Oksana Ross, Sharon R. Rusyn, Ivan Beland, Frederick A. Pogribny, Igor P. TI Dietary Methyl Deficiency, microRNA Expression and Susceptibility to Liver Carcinogenesis SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR; CYCLOOXYGENASE-2 EXPRESSION; GENE-EXPRESSION; BREAST-CANCER; IN-VIVO; APOPTOSIS; CELLS; DISEASE; ACTIVATION C1 [Starlard-Davenport, Athena; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Kosyk, Oksana; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Ross, Sharon R.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI Rusyn, Ivan/S-2426-2016 FU NIEHS NIH HHS [P30 ES010126] NR 48 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2010 VL 3 IS 4-6 BP 259 EP 266 DI 10.1159/000324362 PG 8 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 751LA UT WOS:000289617900013 PM 21474957 ER PT J AU Hartman, TJ Albert, PS Zhang, ZY Bagshaw, D Kris-Etherton, PM Ulbrecht, J Miller, CK Bobe, G Colburn, NH Lanza, E AF Hartman, Terryl J. Albert, Paul S. Zhang, Zhiying Bagshaw, Deborah Kris-Etherton, Penny M. Ulbrecht, Jan Miller, Carla K. Bobe, Gerd Colburn, Nancy H. Lanza, Elaine TI Consumption of a Legume-Enriched, Low-Glycemic Index Diet Is Associated with Biomarkers of Insulin Resistance and Inflammation among Men at Risk for Colorectal Cancer SO JOURNAL OF NUTRITION LA English DT Article ID C-REACTIVE PROTEIN; POLYP PREVENTION TRIAL; BODY-MASS INDEX; METABOLIC SYNDROME; DIABETES-MELLITUS; HIGH-FIBER; SYSTEMIC INFLAMMATION; OXIDATIVE STRESS; PLASMA-GLUCOSE; WOMENS HEALTH AB The Legume Inflammation Feeding Experiment is, to our knowledge, the first randomized crossover feeding trial testing the effects of a legume-enriched, low-glycemic index (GI) diet among men characterized for colorectal adenomas and insulin resistance (IR) status. This study was designed to test the effects of a legume-enriched diet compared with a healthy American (HA) diet under weight-stable conditions. The primary objective was to assess effects on C-reactive protein (CRP) and C-peptide levels. The secondary objective was to assess changes by IR status or history of adenomas. A total of 64 men who completed a colonoscopy within the previous 2 y consumed 2 diets in random order each for 4 wk separated by a washout period. The diets were a legume-enriched (250 g/d), low-GI (GI 38) diet and a high-GI (GI 69) HA diet. We measured fasting glucose, insulin, C-peptide, CRP, and soluble tumor necrosis factor-alpha receptors I and II (sTNFRI/II) at the beginning and end of the diet periods. Participants who consumed both the legume and HA diets had favorably improved CRP (-20.2 and -18.3%) and sTNFRI (-3.7 and -4.4%) concentrations, respectively. The sTNFRII concentrations declined marginally during the legume diet period (-3.8%; P = 0.060) and significantly during the HA diet period (-5.1%; P < 0.001). Fasting glucose increased significantly during both the legume (+1.8%) and HA (-2.2%) diet periods. Only the changes in glucose differed between the diet periods. Serum C-peptide and plasma insulin levels did not change in participants consuming either diet. Healthful dietary changes can improve biomarkers of IR and inflammation. J. Nutr. 140: 60-67, 2010. C1 [Hartman, Terryl J.; Zhang, Zhiying; Bagshaw, Deborah; Kris-Etherton, Penny M.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16870 USA. [Ulbrecht, Jan] Penn State Univ, Dept Biobehav Hlth & Med, University Pk, PA 16870 USA. [Albert, Paul S.] NCI, Div Canc Treatment & Diag, Biometr Res Branch, Bethesda, MD 20892 USA. [Bobe, Gerd; Colburn, Nancy H.; Lanza, Elaine] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. [Miller, Carla K.] Ohio State Univ, Columbus, OH 43210 USA. RP Hartman, TJ (reprint author), Penn State Univ, Dept Nutr Sci, University Pk, PA 16870 USA. EM tjh9@psu.edu FU National Cancer Institute [25XS101]; General Clinical Research Center at Penn State University [M01 FIR 10732] FX Supported by the National Cancer Institute (subcontract 25XS101) with partial support provided by the General Clinical Research Center at Penn State University (NIH grant no. M01 FIR 10732). NR 44 TC 33 Z9 34 U1 0 U2 7 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2010 VL 140 IS 1 BP 60 EP 67 DI 10.3945/jn.109.114249 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 535EH UT WOS:000272949100011 PM 19889807 ER PT J AU Morris, MS Sakakeeny, L Jacques, PF Picciano, MF Selhub, J AF Morris, Martha Savaria Sakakeeny, Lydia Jacques, Paul F. Picciano, Mary Frances Selhub, Jacob TI Vitamin B-6 Intake Is Inversely Related to, and the Requirement Is Affected by, Inflammation Status SO JOURNAL OF NUTRITION LA English DT Article ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; TRANSIENT ISCHEMIC ATTACK; MYOCARDIAL-INFARCTION; FOLIC-ACID; HOMOCYSTEINE METABOLISM; RHEUMATOID-ARTHRITIS; PYRIDOXAL-PHOSPHATE; LYMPHOCYTE-PROLIFERATION; PLASMA HOMOCYSTEINE AB Low circulating pyridoxal 5'-phosphate (PLP) concentrations have been linked to inflammatory markers and the occurrence of inflammatory diseases. However, the implications of these findings are unclear. The measurement of PLP and C-reactive protein (CRP) in blood samples collected from participants in the 2003-2004 NHANES afforded us the opportunity to investigate this relationship in the general U.S. population. Dietary and laboratory data were available for 3864 of 5041 interviewed adults, 2686 of whom were eligible (i.e. provided reliable dietary data and were not diabetic, pregnant, lactating, or taking hormones or steroidal antiinflammatory drugs). Vitamin B-6 intake was assessed using 2 24-h diet recalls and supplement use data. After multivariate adjustment for demographics, smoking, BMI, alcohol use, antioxidant vitamin status, intakes of protein and energy, and serum concentrations of creatinine and albumin, high vitamin B-6 intake was associated with protection against serum CRIP concentrations > 10 mg/L compared with <= 3 mg/L. However, plasma PLP >= 20 nmol/L compared with <20 nmol/L was inversely related to serum CRP independently of vitamin B-6 intake (P < 0.001). Among participants with vitamin B-6 intakes from 2 to 3 mg/d, the multivariate-adjusted prevalence of vitamin B-6 inadequacy was <10% in participants with serum CRP <= 3 mg/L but close to 50% in those with serum CRP > 10 mg/L (P < 0.001). In conclusion, higher vitamin B-6 intakes were linked to protection against inflammation and the vitamin B-6 intake associated with maximum protection against vitamin B-6 inadequacy was increased in the presence compared to absence of inflammation. J. Nutr. 140: 103-110, 2010. C1 [Morris, Martha Savaria; Jacques, Paul F.] Tufts Univ, Nutr Epidemiol Program, Boston, MA 02111 USA. [Sakakeeny, Lydia; Selhub, Jacob] Tufts Univ, Vitamin Metab Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Morris, MS (reprint author), Tufts Univ, Nutr Epidemiol Program, Boston, MA 02111 USA. EM martha.morris@tufts.edu FU NIH [Y1-OD-6516-01]; USDA [58-1950-7-707] FX Supported by NIH agreement no. Y1-OD-6516-01 and USDA agreement no. 58-1950-7-707. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the USDA. NR 74 TC 41 Z9 41 U1 3 U2 11 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2010 VL 140 IS 1 BP 103 EP 110 DI 10.3945/jn.109.114397 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 535EH UT WOS:000272949100017 PM 19906811 ER PT J AU Freedman, LS Guenther, PM Dodd, KW Krebs-Smith, SM Midthune, D AF Freedman, Laurence S. Guenther, Patricia M. Dodd, Kevin W. Krebs-Smith, Susan M. Midthune, Douglas TI The Population Distribution of Ratios of Usual Intakes of Dietary Components That Are Consumed Every Day Can Be Estimated from Repeated 24-Hour Recalls SO JOURNAL OF NUTRITION LA English DT Article ID FOODS AB Estimating the population distribution of the usual intake of a nutrient relative to that of another nutrient requires determination of individual-level ratios. If intake data are available on a per-day basis, as with 24-h dietary recalls, those ratios can be determined in 1 of 2 ways: as the usual ratio of intakes or the ratio of usual intakes. Each of these ratios has its own meaning and determination; the ratio of usual intakes is conceptually consistent with determinations obtained from FFQ data. We present a method for estimating the ratio of usual intakes that uses bivariate modeling of the 2 nutrient intakes in question. Application of the method to the NHANES data for the years 2001-2004 yielded estimated distributions for percent of usual energy intake from total fat, percent of usual energy intake from saturated fat, and usual sodium intake per 1000 kcal (4184 kJ) of usual energy intake. Distributions for both the total population and for age-gender subgroups were estimated. Approximately 60% of adults (>19 y) had a usual total fat intake that was within the recommended range of 20-35% of total energy, but only similar to 34% had a usual saturated fat intake <10% of total energy. The results changed only minimally when the other definition of usual intake, the usual ratio of intakes, was adopted. J. Nutr. 140: 111-116, 2010. C1 [Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. [Guenther, Patricia M.] USDA, Ctr Nutr Policy & Promot, Alexandria, VA 22302 USA. [Dodd, Kevin W.; Krebs-Smith, Susan M.; Midthune, Douglas] NCI, Bethesda, MD 20892 USA. RP Freedman, LS (reprint author), Gertner Inst Epidemiol & Hlth Policy Res, IL-52161 Tel Hashomer, Israel. EM lsf@actcom.co.il FU Information Management Systems Inc; US National Cancer Institute; USDA; National Cancer Institute FX L.S.F. was supported through a contract held by Information Management Systems Inc with the US National Cancer Institute; the remaining authors were supported by their respective institutions: USDA and the National Cancer Institute. NR 15 TC 22 Z9 26 U1 0 U2 1 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2010 VL 140 IS 1 BP 111 EP 116 DI 10.3945/jn.109.110254 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 535EH UT WOS:000272949100018 PM 19923394 ER PT J AU Srinivas, PR Philbert, M Vu, TQ Huang, QR Kokini, JL Saos, E Chen, HD Peterson, CM Friedl, KE McDade-Ngutter, C Hubbard, V Starke-Reed, P Miller, N Betz, JM Dwyer, J Milner, J Ross, SA AF Srinivas, Pothur R. Philbert, Martin Vu, Tania Q. Huang, Qingrong Kokini, Josef L. Saos, Etta Chen, Hongda Peterson, Charles M. Friedl, Karl E. McDade-Ngutter, Crystal Hubbard, Van Starke-Reed, Pamela Miller, Nancy Betz, Joseph M. Dwyer, Johanna Milner, John Ross, Sharon A. TI Nanotechnology Research: Applications in Nutritional Sciences SO JOURNAL OF NUTRITION LA English DT Article ID FOOD; CELLS AB The tantalizing potential of nanotechnology is to fabricate and combine nanoscale approaches and building blocks to make useful tools and, ultimately, interventions for medical science, including nutritional science, at the scale of similar to 1-100 nm. In the past few years, tools and techniques that facilitate studies and interventions in the nanoscale range have become widely available and have drawn widespread attention. Recently, investigators in the food and nutrition sciences have been applying the tools of nanotechnology in their research. The Experimental Biology 2009 symposium entitled "Nanotechnology Research: Applications in Nutritional Sciences" was organized to highlight emerging applications of nanotechnology to the food and nutrition sciences, as well as to suggest ways for further integration of these emerging technologies into nutrition research. Speakers focused on topics that included the problems and possibilities of introducing nanoparticles in clinical or nutrition settings, nanotechnology applications for increasing bioavailability of bioactive food components in new food products, nanotechnology opportunities in food science, as well as emerging safety and regulatory issues in this area, and the basic research applications such as the use of quantum dots to visualize cellular processes and protein-protein interactions. The session highlighted several emerging areas of potential utility in nutrition research. Nutrition scientists are encouraged to leverage ongoing efforts in nanomedicine through collaborations. These efforts could facilitate exploration of previously inaccessible cellular compartments and intracellular pathways and thus uncover strategies for new prevention and therapeutic modalities. J. Nutr. 140: 119-124, 2010. C1 [Milner, John; Ross, Sharon A.] NCI, Canc Prevent Div, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. [Srinivas, Pothur R.] NHLBI, Atherothrombosis & Coronary Artery Dis Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [McDade-Ngutter, Crystal; Hubbard, Van; Starke-Reed, Pamela] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Miller, Nancy] NIH, Off Sci Policy Anal, Off Sci Policy, Off Director, Bethesda, MD 20892 USA. [Betz, Joseph M.; Dwyer, Johanna] NIH, Off Dietary Supplements, Off Director, Bethesda, MD 20892 USA. [Philbert, Martin] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Vu, Tania Q.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Huang, Qingrong] Rutgers State Univ, New Brunswick, NJ 08901 USA. [Kokini, Josef L.] Univ Illinois, Urbana, IL 61801 USA. [Saos, Etta; Chen, Hongda] USDA, Natl Inst Food & Agr, Washington, DC 20024 USA. [Peterson, Charles M.; Friedl, Karl E.] USA, Med Res & Mat Command, Telemed & Adv Technol Res Ctr, Ft Detrick, MD 21702 USA. [Dwyer, Johanna] Tufts Univ, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Ross, SA (reprint author), NCI, Canc Prevent Div, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. EM rosssha@mail.nih.gov OI Dwyer, Johanna/0000-0002-0783-1769; Friedl, Karl/0000-0002-3134-8427 FU NIEHS NIH HHS [R01 ES008846] NR 21 TC 28 Z9 28 U1 1 U2 21 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2010 VL 140 IS 1 BP 119 EP 124 DI 10.3945/jn.109.115048 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 535EH UT WOS:000272949100020 PM 19939997 ER PT J AU Cheng, YS Zhou, Y Naar, J Irvin, CM Su, WC Fleming, LE Kirkpatrick, B Pierce, RH Backer, LC Baden, DG AF Cheng, Yung Sung Zhou, Yue Naar, Jerome Irvin, C. Mitch Su, Wei-Chung Fleming, Lora E. Kirkpatrick, Barbara Pierce, Richard H. Backer, Lorraine C. Baden, Daniel G. TI Personal Exposure to Aerosolized Red Tide Toxins (Brevetoxins) SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE aerosol; personal aerosol sampler; personal exposure ID MARINE AEROSOL; EVENTS; SAMPLERS; ASTHMA AB Florida red tides occur annually in the Gulf of Mexico from blooms of the marine dinoflagellate, Karenia brevis, which produces highly potent natural polyether toxins, brevetoxins. Several epidemiologic studies have demonstrated that human exposure to red tide aerosol could result in increased respiratory symptoms. Environmental monitoring of aerosolized brevetoxins was performed using a high-volume sampler taken hourly at fixed locations on Siesta Beach, Florida. Personal exposure was monitored using personal air samplers and taking nasal swab samples from the subjects who were instructed to spend 1 hr on Sarasota Beach during two sampling periods of an active Florida red tide event in March 2005, and in May 2008 when there was no red tide. Results showed that the aerosolized brevetoxins from the personal sampler were in modest agreement with the environmental concentration taken from a high-volume sampler. Analysis of nasal swab samples for brevetoxins demonstrated 68% positive samples in the March 2005 sampling period when air concentrations of brevetoxins were between 50 to 120 ng/m3 measured with the high-volume sampler. No swab samples showed detectable levels of brevetoxins in the May 2008 study, when all personal samples were below the limit of detection. However, there were no statistical correlations between the amounts of brevetoxins detected in the swab samples with either the environmental or personal concentration. Results showed that the personal sample might provide an estimate of individual exposure level. Nasal swab samples showed that brevetoxins indeed were inhaled and deposited in the nasal passage during the March 2005 red tide event. C1 [Cheng, Yung Sung; Zhou, Yue; Irvin, C. Mitch; Su, Wei-Chung] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. [Naar, Jerome; Baden, Daniel G.] Univ N Carolina, Ctr Marine Sci, Wilmington, NC 28401 USA. [Fleming, Lora E.] Univ Miami, NSF NIEHS Oceans, Miami, FL USA. [Fleming, Lora E.] Univ Miami, Human Hlth Sci Ctr, Miami, FL USA. [Kirkpatrick, Barbara; Pierce, Richard H.] Mote Marine Lab, Sarasota, FL 34236 USA. [Backer, Lorraine C.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Cheng, YS (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrest Dr,SE, Albuquerque, NM 87108 USA. EM ycheng@lrri.org FU National Institute of Environmental Health Sciences (NIEHS) [P01-ES10594]; National Institute for Occupational Safety and Health [R01 OH03900]; U.S. Centers for Disease Control and Prevention; Florida Department of Health FX T he authors would like to thank A. Weidner (University of North Carolina at Wilmington) for the ELISA analysis; D. Dalpra and K Nierenberg (Mote Marine Lab) for recruiting and working with the study participants; and M. Henry (Mote Marine Lab) for help in environmental monitoring. This research was supported by the National Institute of Environmental Health Sciences (NIEHS) program project P01-ES10594, the National Institute for Occupational Safety and Health grant R01 OH03900, the U.S. Centers for Disease Control and Prevention, and the Florida Department of Health. NR 15 TC 0 Z9 0 U1 1 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PY 2010 VL 7 IS 6 BP 326 EP 331 AR PII 921030290 DI 10.1080/15459621003724041 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 594NO UT WOS:000277544600003 PM 20379895 ER PT J AU Lemon, SC Pratt, CA AF Lemon, Stephenie C. Pratt, Charlotte A. TI Worksite Environmental Interventions for Obesity Control: An Overview SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID HEALTH PROMOTION; US ADULTS; METAANALYSIS; PREVENTION AB In 2004, the National Heart, Lung, and Blood Institute funded seven independent research projects to test the effectiveness of multicomponent weight control interventions at worksites that include environmental changes alone or in combination with individually targeted strategies (Pratt et al, Obesity. 2007;15:2171-2180). The studies were conducted in a variety of worksites across the United States. This supplement to the Journal of Occupation and Environmental Medicine includes a series of manuscripts that evaluate various aspects of the funded studies, including environmental and cost-related findings, process evaluation, and the impact of acute and chronic psychosocial work stressors on body mass index. C1 [Lemon, Stephenie C.] Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01655 USA. [Pratt, Charlotte A.] NHLBI, Prevent & Populat Sci Program, NIH, Bethesda, MD 20892 USA. RP Lemon, SC (reprint author), Univ Massachusetts, Sch Med, Div Prevent & Behav Med, S7-745, Worcester, MA 01655 USA. EM stephenie.lemon@umassmed.edu FU NHLBI NIH HHS [R01 HL079483] NR 26 TC 6 Z9 6 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JAN PY 2010 VL 52 IS 1 SU S BP S1 EP S3 DI 10.1097/JOM.0b013e3181c8527e PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 543LL UT WOS:000273578900001 PM 20061881 ER PT J AU Tang, J Rivers, MB Moshfeghi, AA Flynn, HW Chan, CC AF Tang, Johnny Rivers, Michael B. Moshfeghi, Andrew A. Flynn, Harry W., Jr. Chan, Chi-Chao TI Pathology of Macular Foveoschisis Associated with Degenerative Myopia SO JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTERNAL LIMITING MEMBRANE; OPTICAL COHERENCE TOMOGRAPHY; RETINAL-DETACHMENT; RETINOSCHISIS; EYES; VITRECTOMY; TRACTION; HOLE AB This is a clinicopathological paper on the histologic findings in myopia-associated macular foveoschisis. The findings on ophthalmic pathological study of a 73-year-old woman with high myopia are reviewed. Multiple retinoschisis cavities involving both the macula and retinal periphery were disclosed. Our paper offers tissue evidence and supports recent ocular coherence tomography reports of eyes with high myopia and associated macular foveoschisis. C1 [Tang, Johnny] Louis Stokes Cleveland VA Med Ctr, Res Serv, Cleveland, OH 44106 USA. [Tang, Johnny] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Univ Hosp Eye Inst, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Rivers, Michael B.] Retina Grp Washington, Fairfax, VA 22031 USA. [Moshfeghi, Andrew A.; Flynn, Harry W., Jr.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 USA. [Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Tang, J (reprint author), Louis Stokes Cleveland VA Med Ctr, Res Serv, Cleveland, OH 44106 USA. EM bostonretina@aol.com FU Veterans Affairs Career Development Award 2, Veterans Affairs Foundation Award; NEI Intramural Research Program FX This work was supported in part by the Veterans Affairs Career Development Award 2, Veterans Affairs Foundation Award, and the NEI Intramural Research Program. NR 18 TC 10 Z9 10 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2010 AR 175613 DI 10.1155/2010/175613 PG 4 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA V24II UT WOS:000208403700007 ER PT J AU Singh, AJ Xu, CX Xu, XM West, LM Wilmes, A Chan, A Hamel, E Miller, JH Northcote, PT Ghosh, AK AF Singh, A. Jonathan Xu, Chun-Xiao Xu, Xiaoming West, Lyndon M. Wilmes, Anja Chan, Ariane Hamel, Ernest Miller, John H. Northcote, Peter T. Ghosh, Arun K. TI Peloruside B, A Potent Antitumor Macrolide from the New Zealand Marine Sponge Mycale hentscheli: Isolation, Structure, Total Synthesis, and Bioactivity SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID MICROTUBULE-STABILIZING AGENT; DIASTEREOMER-DISCRIMINATING RCM; MYCALAMIDE-A; STEREOSELECTIVE-SYNTHESIS; ANTIMITOTIC AGENT; NATURAL-PRODUCTS; TAXOID SITE; CELL-LINES; FRAGMENT; SEGMENT AB Peloruside B (2), a natural congener of peloruside A (1), was isolated in sub-milligram quantities from the New Zealand marine sponge Mycale hentscheli. Peloruside B promotes microtubule polymerization and arrests cells in the G(2)/M phase of mitosis similar to paclitaxel, and its bioactivity was comparable to that of peloruside A. NMR-directed isolation, structure elucidation, structure confirmation by total synthesis, and bioactivity of peloruside B are described in this article. The synthesis features Sharpless dihydroxylation, Brown's asymmetric allylboration reaction, reductive aldol coupling, Yamaguchi macrolactonization, and selective methylation. C1 [Singh, A. Jonathan; Wilmes, Anja; Chan, Ariane; Miller, John H.; Northcote, Peter T.] Victoria Univ Wellington, Ctr Biodiscovery, Wellington, New Zealand. [Xu, Chun-Xiao; Xu, Xiaoming; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Xu, Chun-Xiao; Xu, Xiaoming; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [West, Lyndon M.] Florida Atlantic Univ, Dept Chem & Biochem, Boca Raton, FL 33431 USA. RP Northcote, PT (reprint author), Victoria Univ Wellington, Ctr Biodiscovery, Wellington, New Zealand. EM peter.northcote@vuw.ac.nz; akghosh@purdue.edu OI zaraat, javad/0000-0001-5341-7481; Wilmes, Anja/0000-0001-9485-4565 FU National Institutes of Health and Purdue University; NZ Foundation for Research, Science & Technology (FRST); Cancer Society of New Zealand; Curtis-Gordon Research Scholarship in Chemistry; Wellington Medical Research Foundation; NZ Genesis Oncology FX Financial support of this work was provided in part by the National Institutes of Health and Purdue University, The NZ Foundation for Research, Science & Technology (FRST), Cancer Society of New Zealand and Curtis-Gordon Research Scholarship in Chemistry (VUW) are acknowledged for funding (A.J.S.). We also thank the Wellington Medical Research Foundation and a NZ Genesis Oncology Postgraduate Scholarship (A.C.). The authors thank Dr. John Ryan (VUW), and Dr. John Harwood (Purdue University) for assistance with the NMR structure analysis. NR 42 TC 28 Z9 28 U1 1 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JAN 1 PY 2010 VL 75 IS 1 BP 2 EP 10 DI 10.1021/jo9021265 PG 9 WC Chemistry, Organic SC Chemistry GA 536AG UT WOS:000273013000002 PM 19957922 ER PT J AU Bougel, S Renaud, S Braunschweig, R Loukinov, D Morse, HC Bosman, FT Lobanenkov, V Benhattar, J AF Bougel, Stephanie Renaud, Stephanie Braunschweig, Richard Loukinov, Dmitri Morse, Herbert C., III Bosman, Fred T. Lobanenkov, Victor Benhattar, Jean TI PAX5 activates the transcription of the human telomerase reverse transcriptase gene in B cells SO JOURNAL OF PATHOLOGY LA English DT Article DE hTERT; PAX5; B cells; chromatin immunoprecipitation; CTCF; telomerase; DNA methylation ID CATALYTIC SUBUNIT; DNA METHYLATION; BSAP PAX-5; HTERT GENE; TERNARY COMPLEXES; CTCF-BINDING; CPG ISLAND; IGH LOCUS; PCR-SSCP; PROMOTER AB Telomerase is an RNA-dependent DNA polymerase that synthesizes telomeric DNA. Its activity is not detectable in most somatic cells but it is reactivated during tumorigenesis. In most cancers, the combination of hTERT hypermethylation and hypomethylation of a short promoter region is permissive for low-level hTERT transcription. Activated and malignant lymphocytes express high telomerase activity, through a mechanism that seems methylation-independent. The aim of this study was to determine which mechanism is involved in the enhanced expression of hTERT in lymphoid cells. Our data confirm that in B cells, some T cell lymphomas and non-neoplastic lymph nodes, the hTERT promoter is unmethylated. Binding sites for the B cell-specific transcription factor PAX5 were identified downstream of the ATG translational start site through EMSA and ChIP experiments. ChIP assays indicated that the transcriptional activation of hTERT by PAX5 does not involve repression of CTCF binding. In a B cell lymphoma cell line, siRNA-induced knockdown of PAX5 expression repressed hTERT transcription. Moreover, ectopic expression of PAX5 in a telomerase-negative normal fibroblast cell line was found to be sufficient to activate hTERT expression. These data show that activation of hTERT in telomerase-positive B cells is due to a methylation-independent mechanism in which PAX5 plays all important role. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Bougel, Stephanie; Braunschweig, Richard; Bosman, Fred T.; Benhattar, Jean] CHU Vaudois, Inst Pathol, CH-1011 Lausanne, Switzerland. [Bougel, Stephanie; Braunschweig, Richard; Bosman, Fred T.; Benhattar, Jean] Univ Lausanne, CH-1011 Lausanne, Switzerland. [Renaud, Stephanie; Loukinov, Dmitri; Morse, Herbert C., III; Lobanenkov, Victor] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. RP Benhattar, J (reprint author), CHU Vaudois, Inst Pathol, Bugnon 25, CH-1011 Lausanne, Switzerland. EM Jean.Benhattar@chuv.ch OI Morse, Herbert/0000-0002-9331-3705; Lobanenkov, Victor/0000-0001-6665-3635 FU Swiss National Science Foundation [3100A0-101732, 3100A0-113505]; NIH; National Institute of Allergy and Infectious Diseases FX This work was supported by grants from the Swiss National Science Foundation (Grants 3100A0-101732 and 3100A0-113505) and in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 45 TC 12 Z9 14 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2010 VL 220 IS 1 BP 87 EP 96 DI 10.1002/path.2620 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 538LN UT WOS:000273186100010 PM 19806612 ER PT J AU Bell, DW AF Bell, Daphne W. TI Our changing view of the genomic landscape of cancer SO JOURNAL OF PATHOLOGY LA English DT Review DE neoplasia; gene; sequence; mutation; history; cancer; somatic; genomic; personalized medicine ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; METASTATIC BREAST-CANCER; GROWTH-FACTOR RECEPTOR; KINASE GENE FAMILY; ACUTE LYMPHOBLASTIC-LEUKEMIA; BLADDER-CARCINOMA ONCOGENE; TUBEROUS SCLEROSIS GENE; TUMOR-SUPPRESSOR GENE; ABL TYROSINE KINASE AB Sporadic tumours, which account for the majority of all human cancers, arise from the acquisition of somatic, genetic and epigenetic alterations leading to changes in gene sequence, structure, copy number and expression. Within the last decade, the availability of a complete sequence-based map of the human genome, coupled with significant technological advances, has revolutionized the search for somatic alterations in tumour genomes. Recent landmark studies, which resequenced all coding exons within breast, colorectal, brain and pancreatic cancers, have shed new light on the genomic landscape of cancer. Within a given tumour type there are many infrequently mutated genes and a few frequently mutated genes, resulting in incredible genetic heterogeneity. However, when the altered genes are placed into biological processes and biochemical pathways, this complexity is significantly reduced and shared pathways that are affected in significant numbers of tumours can be discerned. The advent of next-generation sequencing technologies has opened up the potential to resequence entire tumour genomes to interrogate protein-encoding genes, non-coding RNA genes, non-genic regions and the mitochondrial genome. During the next decade it is anticipated that the most common forms of human cancer will be systematically surveyed to identify the underlying somatic changes in gene copy number, sequence and expression. The resulting catalogues of somatic alterations will point to candidate cancer genes requiring further validation to determine whether they have a causal role in tumourigenesis. The hope is that this knowledge will fuel improvements in cancer diagnosis, prognosis and therapy, based on the specific molecular alterations that drive individual tumours. In this review, I will provide a historical perspective on the identification of somatic alterations in the pre- and post-genomic eras, with a particular emphasis on recent pioneering studies that have provided unprecedented insights into the genomic landscape of human cancer. Published in 2009 by John Wiley & Sons, Ltd. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM belldaph@mail.nih.gov FU NIH FX I would like to extend my sincere thanks to Dr Cariappa Annaiah and members of my laboratory for critical reading of the manuscript. I thank Julia Fekecs and Darryl Leja for graphical expertise. Funded by the Intramural Program of the National Human Genome Research Institute at NIH (to DWB). NR 242 TC 48 Z9 49 U1 2 U2 17 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2010 VL 220 IS 2 BP 231 EP 243 DI 10.1002/path.2645 PG 13 WC Oncology; Pathology SC Oncology; Pathology GA 545CM UT WOS:000273710100011 PM 19918804 ER PT J AU Bedognetti, D Rubagotti, A Zoppoli, G Boccardo, F AF Bedognetti, Davide Rubagotti, Alessandra Zoppoli, Gabriele Boccardo, Francesco TI Gynaecomastia: The Anastrozole Paradox SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Letter ID PUBERTAL GYNECOMASTIA; PROSTATE-CANCER; BREAST PAIN; TAMOXIFEN; BICALUTAMIDE; PREVENTION C1 [Bedognetti, Davide; Rubagotti, Alessandra; Zoppoli, Gabriele; Boccardo, Francesco] Univ Study Genoa, Genoa, Italy. [Rubagotti, Alessandra; Boccardo, Francesco] Natl Canc Res Inst, Genoa, Italy. [Bedognetti, Davide; Zoppoli, Gabriele] NIH, Bethesda, MD 20892 USA. RP Bedognetti, D (reprint author), Univ Study Genoa, Genoa, Italy. EM Davide.Bedognetti@nih.gov RI Bedognetti, Davide/A-9090-2012; Zoppoli, Gabriele/B-6935-2016; OI Zoppoli, Gabriele/0000-0003-3890-5588; Bedognetti, Davide/0000-0002-5857-773X NR 9 TC 1 Z9 1 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD JAN-FEB PY 2010 VL 23 IS 1-2 BP 205 EP 206 PG 2 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 582NO UT WOS:000276604900028 PM 20432826 ER PT J AU Mazaki-Tovi, S Romero, R Vaisbuch, E Chaiworapongsa, T Erez, O Mittal, P Kim, SK Gotsch, F Lamont, R Ogge, G Pacora, P Goncalves, L Kim, CJ Gomez, R Espinoza, J Hassan, SS Kusanovic, JP AF Mazaki-Tovi, Shali Romero, Roberto Vaisbuch, Edi Chaiworapongsa, Tinnakorn Erez, Offer Mittal, Pooja Kim, Sun Kwon Gotsch, Francesca Lamont, Ronald Ogge, Giovanna Pacora, Percy Goncalves, Luis Kim, Chong Jai Gomez, Ricardo Espinoza, Jimmy Hassan, Sonia S. Kusanovic, Juan Pedro TI Low circulating maternal adiponectin in patients with pyelonephritis: adiponectin at the crossroads of pregnancy and infection SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Acute bacterial infection; adipokines; adiponectin; infection; inflammation; pregnancy; pyelonephritis ID RESPIRATORY-DISTRESS-SYNDROME; ACTIVATED PROTEIN-KINASE; ADIPOSE-SPECIFIC PROTEIN; TYPE-2 DIABETIC-PATIENTS; METABOLIC RISK-FACTORS; INSULIN-RESISTANCE; PLASMA-PROTEIN; SERUM ADIPONECTIN; AMNIOTIC-FLUID; STIMULATES ANGIOGENESIS AB Objective: An emerging theme in modern biology is that adipose tissue can respond to metabolic stress, and to inflammatory stimuli, by regulating the secretion of a complex network of soluble mediators, termed adipokines. Adiponectin, the most prevalent circulating adipokine in human, has profound insulin-sensitizing and anti-inflammatory properties. Indeed, the notion that adiponectin plays an important role in the interactions between the metabolic and the immune systems has been strongly suggested. Thus, the aim of this study was to determine if pyelonephritis during pregnancy is associated with changes in maternal serum adiponectin concentrations. Study design: This cross-sectional study included women in the following groups: 1) normal pregnant women (n=200); and 2) pregnant women with pyelonephritis (n=50). Maternal plasma adiponectin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results: 1) The median maternal plasma adiponectin concentration was lower in patients with pyelonephritis than in those with a normal pregnancy (P<0.001); 2) among pregnant women with a normal weight, patients with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (P<0.001); 3) similarly, among overweight/obese patients, those with pyelonephritis had a lower median plasma adiponectin concentration than those with a normal pregnancy (P<0.001); and 4) the presence of pyelonephritis was independently associated with maternal plasma adiponectin concentrations after adjustment for maternal age, smoking, gestational age at sampling, and pregestational body mass index (BMI). Conclusion: 1) The findings that acute pyelonephritis in pregnancy is characterized by low maternal plasma concentrations of adiponectin in both lean and overweight/obese patients are novel and concur with the antiinflammatory properties of adiponectin; and 2) the results of this study support the notion that adiponectin may play a role in the intricate interface between inflammation and metabolism during pregnancy. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Kim, Sun Kwon; Gotsch, Francesca; Lamont, Ronald; Ogge, Giovanna; Pacora, Percy; Goncalves, Luis; Kim, Chong Jai; Espinoza, Jimmy; Hassan, Sonia S.; Kusanovic, Juan Pedro] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Erez, Offer; Mittal, Pooja; Lamont, Ronald; Hassan, Sonia S.; Kusanovic, Juan Pedro] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Hosp Sotero Rio, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU National Institute of Child Health and Human Development, NIH, DHHS FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 127 TC 13 Z9 13 U1 0 U2 3 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD JAN PY 2010 VL 38 IS 1 BP 9 EP 17 DI 10.1515/JPM.2009.134 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 547SZ UT WOS:000273910800003 PM 19650757 ER PT J AU Lee, SE Romero, R Lee, SM Yoon, BH AF Lee, Si Eun Romero, Roberto Lee, Seung Mi Yoon, Bo Hyun TI Amniotic fluid volume in intra-amniotic inflammation with and without culture-proven amniotic fluid infection in preterm premature rupture of membranes SO JOURNAL OF PERINATAL MEDICINE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med (SMFM) DE Amniotic fluid index (AFI); amniotic fluid infection; fetal inflammatory response syndrome (FIRS); intra-amniotic inflammation; oligohydramnios; rupture of membranes ID POLYMERASE-CHAIN-REACTION; MATRIX METALLOPROTEINASE-8; INTRAUTERINE INFECTION; CLINICAL-SIGNIFICANCE; RESPONSE SYNDROME; SPONTANEOUS LABOR; FETAL; PREGNANCY; OLIGOHYDRAMNIOS; ASSOCIATION AB Objective: Previous studies reported that the clinical significance of intra-amniotic inflammation with a negative amniotic fluid (AF) culture is similar to that of intra-amniotic inflammation with microbiologically-proven AF infection. However, the magnitude of the fetal inflammatory response in these two conditions is different as gauged by umbilical cord C-reactive protein (CRP) concentrations. We undertook this study to determine if the frequency of oligohydramnios is different in these two conditions. Methods: The amniotic fluid index (AFI) was measured in 205 patients with preterm premature rupture of membranes (PROM) (<= 35 weeks). AF was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an elevated AF matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). Patients were divided into three groups according to the results of AF culture and the presence or absence of intra-amniotic inflammation: 1) without intra-amniotic inflammation and a negative culture (n=109); 2) with intra-amniotic inflammation and a negative culture (n=44); and 3) a positive culture (n=52). Results: Patients with a positive culture had a higher frequency of oligohydramnios and a lower median AFI than those with a negative culture but with intra-amniotic inflammation (P<0.01). However, there was no significant difference in the median AFI or in the frequency of oligohydramnios according to the presence or absence of intra-amniotic inflammation among patients with a negative culture (P>0.1). Conclusion: Oligohydramnios was more frequent in patients with culture-proven AF infection than in those with intra-amniotic inflammation and a negative AF culture. C1 [Lee, Si Eun; Lee, Seung Mi; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet Gynecol, Seoul 110744, South Korea. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet Gynecol, Seoul 110744, South Korea. EM Yoonbh@snu.ac.kr RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS [Z01 HD002400-16] NR 34 TC 25 Z9 27 U1 0 U2 2 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD JAN PY 2010 VL 38 IS 1 BP 39 EP 44 DI 10.1515/JPM.2009.123 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 547SZ UT WOS:000273910800008 PM 19708825 ER PT J AU Kim, SK Romero, R Kusanovic, JP Erez, O Vaisbuch, E Mazaki-Tovi, S Gotsch, F Mittal, P Chaiworapongsa, T Pacora, P Ogge, G Gomez, R Yoon, BH Yeo, L Lamont, RF Hassan, SS AF Kim, Sun Kwon Romero, Roberto Kusanovic, Juan Pedro Erez, Offer Vaisbuch, Edi Mazaki-Tovi, Shali Gotsch, Francesca Mittal, Pooja Chaiworapongsa, Tinnakorn Pacora, Percy Ogge, Giovanna Gomez, Ricardo Yoon, Bo Hyun Yeo, Lami Lamont, Ronald F. Hassan, Sonia S. TI The prognosis of pregnancy conceived despite the presence of an intrauterine device (IUD) SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE Chorioamnionitis; intrauterine device; microbial invasion of the amniotic cavity; pregnancy; prematurity; preterm delivery; preterm labor; preterm prelabor rupture of the membranes ID PRETERM PREMATURE RUPTURE; AMNIOTIC-FLUID SLUDGE; INTRAAMNIOTIC INFECTION; PLACENTAL ABRUPTION; CLINICAL-SIGNIFICANCE; CONTRACEPTIVE DEVICE; CANDIDA INFECTION; INTACT MEMBRANES; RISK-FACTORS; LABOR AB Objective: Intrauterine devices (IUDs) are used for contraception worldwide; however, the management of pregnancies with an IUD poses a clinical challenge. The purpose of this study was to determine the outcome of pregnancy in patients with an IUD. Study design: A retrospective cohort study (December 1997-June 2007) was conducted. The cohort consisted of 12,297 pregnancies, of which 196 had an IUD. Only singleton pregnancies were included. Logistic regression analysis was used to adjust for potential confounders between the groups. Results: 1) Pregnancies with an IUD were associated with a higher rate of late miscarriage, preterm delivery, vaginal bleeding, clinical chorioamnionitis, and placental abruption than those without an IUD; 2) among patients with available histologic examination of the placenta, the rate of histologic chorioamnionitis and/or funisitis was higher in patients with an IUD than in those without an IUD (54.2% vs. 14.7%; P<0.001). Similarly, among patients who underwent an amniocentesis, the prevalence of microbial invasion of the amniotic cavity (MIAC) was also higher in pregnant women with an IUD than in those without an IUD (45.9% vs. 8.8%; P<0.001); and 3) intra-amniotic infection caused by Candida species was more frequently present in pregnancies with an IUD than in those without an IUD (31.1% vs. 6.3%; P<0.001). Conclusion: Pregnant women with an IUD are at a very high risk for adverse pregnancy outcomes. This finding can be attributed, at least in part, to the high prevalence of intra-amniotic infection and placental inflammatory lesions observed in pregnancies with an IUD. C1 [Kim, Sun Kwon; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Vaisbuch, Edi; Mazaki-Tovi, Shali; Gotsch, Francesca; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Pacora, Percy; Ogge, Giovanna; Yeo, Lami; Lamont, Ronald F.; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Kim, Sun Kwon; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Vaisbuch, Edi; Mazaki-Tovi, Shali; Gotsch, Francesca; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Pacora, Percy; Ogge, Giovanna; Yeo, Lami; Lamont, Ronald F.; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Vaisbuch, Edi; Mazaki-Tovi, Shali; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Yeo, Lami; Lamont, Ronald F.; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Ctr Perinatal Diag & Res CEDIP, Sotero Rio Hosp, Santiago, Chile. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 59 TC 23 Z9 23 U1 1 U2 5 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD JAN PY 2010 VL 38 IS 1 BP 45 EP 53 DI 10.1515/JPM.2009.133 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 547SZ UT WOS:000273910800009 PM 19650756 ER PT J AU Katz, JL Soto, PL Koffarnus, M AF Katz, Jonathan L. Soto, Paul. L. Koffarnus, Mikhail TI Cognitive safety of a benztropine analog with preclinical efficacy for ADHD SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 83rd Annual Meeting of the Japanese-Pharmacological-Society CY MAR 16-18, 2010 CL Osaka, JAPAN SP Japanese Pharmacol Soc C1 [Katz, Jonathan L.] NIDA IRP, Medicat Discovery Res Branch, Baltimore, MD 21224 USA. [Soto, Paul. L.; Koffarnus, Mikhail] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2010 VL 112 SU 1 BP 17P EP 17P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 573NQ UT WOS:000275921000029 ER PT J AU Goto, K Chiba, Y Matsusue, K Sakai, H Kimura, S Misawa, M AF Goto, Kumiko Chiba, Yoshihiko Matsusue, Kimihiko Sakai, Hiroyasu Kimura, Shioko Misawa, Miwa TI Pharmacological studies on the respiratory tract (Rpt. 330): Characterization of the human RhoA gene promoter in bronchial smooth muscle cells SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 83rd Annual Meeting of the Japanese-Pharmacological-Society CY MAR 16-18, 2010 CL Osaka, JAPAN SP Japanese Pharmacol Soc C1 [Goto, Kumiko; Chiba, Yoshihiko; Sakai, Hiroyasu; Misawa, Miwa] Hoshi Univ, Sch Med, Dept Pharmacol, Shinagawa Ku, Tokyo 1428501, Japan. [Matsusue, Kimihiko] Fukuoka Univ, Fac Pharmaceut Sci, Jonan Ku, Fukuoka 8140180, Japan. [Matsusue, Kimihiko; Kimura, Shioko] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2010 VL 112 SU 1 BP 73P EP 73P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 573NQ UT WOS:000275921000245 ER PT J AU Unno, T Yamamoto, M Hayashi, T Koide, K Tanahashi, Y Matsuyama, H Yamada, M Jurgen, W Komori, S AF Unno, Toshihiro Yamamoto, Masayuki Hayashi, Toshimi Koide, Kento Tanahashi, Yasuyuki Matsuyama, Hayato Yamada, Masahisa Jurgen, Wess Komori, Seiichi TI Functional roles of M2 and M3 muscarinic receptors in neurogenic contractions in mouse bladder studied with receptor knockout mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 83rd Annual Meeting of the Japanese-Pharmacological-Society CY MAR 16-18, 2010 CL Osaka, JAPAN SP Japanese Pharmacol Soc C1 [Unno, Toshihiro; Hayashi, Toshimi; Koide, Kento; Matsuyama, Hayato; Komori, Seiichi] Gifu Univ, Dept Vet Med, Pharmacol Lab, Gifu 5011193, Japan. [Yamamoto, Masayuki; Tanahashi, Yasuyuki] Gifu Univ, United Grad Sch, Dept Pathogen Vet Med, Gifu 5011193, Japan. [Yamada, Masahisa] RIKEN, Brain Sci Inst, Yamada Res Unit, Wako, Saitama 3510198, Japan. [Jurgen, Wess] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2010 VL 112 SU 1 BP 193P EP 193P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 573NQ UT WOS:000275921001240 ER PT J AU Baladi, MG Newman, AH France, CP AF Baladi, Michelle G. Newman, Amy H. France, Charles P. TI Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BODY-TEMPERATURE; (+)-PD 128907; AGONISTS; D-3; COCAINE; HYPOTHERMIA; ANTAGONISTS; RACLOPRIDE; LIGANDS; ANALOGS AB The discriminative stimulus effects of dopamine (DA) D3/D2 receptor agonists are thought to be mediated by D2 receptors. To maintain responding, access to food is often restricted, which can alter neurochemical and behavioral effects of drugs acting on DA systems. This study established stimulus control with quinpirole in free-feeding rats and tested the ability of agonists to mimic and antagonists to attenuate the effects of quinpirole. The same antagonists were studied for their ability to attenuate quinpirole-induced yawning and hypothermia. DA receptor agonists apomorphine and lisuride, but not amphetamine and morphine, occasioned responding on the quinpirole lever. The discriminative stimulus effects of quinpirole were attenuated by the D3 receptor-selective antagonist N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide HCl (PG01037) and the nonselective D3/D2 receptor antagonist raclopride, but not by the D2 receptor-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl-1H-indole (L-741,626); the potencies of PG01037 and raclopride to antagonize this effect of quinpirole paralleled their potencies to antagonize the ascending limb of the quinpirole yawning dose-response curve (thought to be mediated by D3 receptors). L-741,626 selectively antagonized the descending limb of the quinpirole yawning dose-response curve, and both L-741,626 and raclopride, but not PG01037, antagonized the hypothermic effects of quinpirole (thought to be mediated by D2 receptors). Food restriction (10 g/day/7 days) significantly decreased quinpirole-induced yawning without affecting the quinpirole discrimination. Many discrimination studies on DA receptor agonists use food-restricted rats; together with those studies, the current experiment using free-feeding rats suggests that feeding conditions affecting the behavioral effects of direct-acting DA receptor agonists might also have an impact on the effects of indirect-acting agonists such as cocaine and amphetamine. C1 [Baladi, Michelle G.; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM france@uthscsa.edu FU National Institutes of Health National Institute on Drug Abuse [DA17918] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health National Institute on Drug Abuse (to A.H.N.); and the National Institutes of Health National Institute on Drug Abuse [Grant DA17918]. NR 36 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2010 VL 332 IS 1 BP 308 EP 315 DI 10.1124/jpet.109.158394 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 534RB UT WOS:000272913900033 PM 19797621 ER PT J AU Kiziltepe, T Anderson, KC Kutok, JL Jia, L Boucher, KM Saavedra, JE Keefer, LK Shami, PJ AF Kiziltepe, Tanyel Anderson, Kenneth C. Kutok, Jeffery L. Jia, Lee Boucher, Kenneth M. Saavedra, Joseph E. Keefer, Larry K. Shami, Paul J. TI JS-K has potent anti-angiogenic activity in vitro and inhibits tumour angiogenesis in a multiple myeloma model in vivo SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article DE angiogenesis; HUVEC; JS-K; myeloma; nitric oxide ID BONE-MARROW ANGIOGENESIS; NITRIC-OXIDE MODULATION; LEUKEMIA-CELLS; S-GLUTATHIONYLATION; PROGNOSTIC VALUE; GENE-EXPRESSION; DIFFERENTIATION; RESISTANCE; APOPTOSIS; GROWTH AB Objectives Glutathione S-transferases (GSTs) play an important role in multidrug resistance and are upregulated in multiple cancers. We have designed a prodrug class that releases nitric oxide on metabolism by GST. O(2-)(2,4-Dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent antineoplastic activity. Methods We studied the effect of JS-K on angiogenesis in human umbilical vein endothelial cells (HUVECs), OPM1 multiple myeloma cells, chick aortic rings and in mice. Key findings JS-K inhibited the proliferation of HUVECs with a 50% inhibitory concentration (IC50) of 0.432, 0.466 and 0.505 mu M at 24, 48 and 72 h, respectively. In the cord formation assay, JS-K led to a decrease in the number of cord junctions and cord length with an IC50 of 0.637 and 0.696 mu M, respectively. JS-K inhibited cell migration at 5 h using VEGF as a chemoattractant. Migration inhibition occurred with an IC50 of 0.493 mu M. In the chick aortic ring assay using VEGF or FGF-2 for vessel growth stimulation, 0.5 mu M JS-K completely inhibited vessel growth. JS-K inhibited tumour angiogenesis in vivo in NIH III mice implanted subcutaneously with OPM1 multiple myeloma cells. Conclusions JS-K is a potent inhibitor of angiogenesis in vitro and tumour vessel growth in vivo. As such, it establishes a new class of antineoplastic agent that targets the malignant cells directly as well as their microenvironment. C1 [Kiziltepe, Tanyel; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Kutok, Jeffery L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kutok, Jeffery L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Jia, Lee] NCI, Dev Therapeut Branch, Rockville, MD USA. [Boucher, Kenneth M.; Shami, Paul J.] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA. [Saavedra, Joseph E.] SAIC Frederick, Frederick, MD USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. [Shami, Paul J.] Univ Utah, Dept Internal Med, Div Med Oncol, Salt Lake City, UT 84112 USA. RP Shami, PJ (reprint author), Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Suite 2100,2000 Circle Hope, Salt Lake City, UT 84112 USA. EM paul.shami@utah.edu RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Boucher, Kenneth/0000-0003-2833-0127 FU Leukemia and Lymphoma Society; NCI RAID; NIH [R01 CA84496, R01 CA129611]; National Cancer Institute [N01-CO-12400]; Center for Cancer Research FX We acknowledge Jagadambal Thillainathan (SAIC-Frederick, Frederick, USA) for technical assistance. This work was funded by the Translational Research Award from the Leukemia and Lymphoma Society, NCI RAID Grant, NIH Grants R01 CA84496 and R01 CA129611 (P.J.S) and the National Cancer Institute contract No. N01-CO-12400. It was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The following contributions were made by the authors: Tanyel Kiziltepe performed research, reviewed and edited the manuscript; Kenneth C. Anderson oversaw research, reviewed and edited the manuscript; Jeffery Kutok performed research, reviewed and edited the manuscript; Lee Jia oversaw research, reviewed and edited the manuscript; Kenneth M. Boucher performed statistical analysis, reviewed and edited the manuscript; Joseph E. Saavedra designed, synthesized and provided JS-K and reviewed and edited the manuscript; Larry K. Keefer designed J-S-K and reviewed and edited the manuscript; Paul J. Shami analysed and interpreted data and wrote the manuscript. NR 25 TC 12 Z9 14 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD JAN PY 2010 VL 62 IS 1 BP 145 EP 151 DI 10.1211/jpp/62.01.0017 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 554XV UT WOS:000274470700017 PM 20723011 ER PT J AU Kurotani, R Kezuka, K Kimura, S Ishikawa, Y AF Kurotani, Reikol Kezuka, Kyohei Kimura, Shioko Ishikawa, Yoshihiro TI SCGB3A2 suppresses bleomycin-induced lung fibrosis through activation of STAT1 SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Kurotani, Reikol; Kezuka, Kyohei; Ishikawa, Yoshihiro] Yokohama City Univ, Inst Cardiovasc Res, Yokohama, Kanagawa 232, Japan. [Kurotani, Reikol; Kimura, Shioko] NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2010 VL 60 SU 1 BP S197 EP S197 PG 1 WC Physiology SC Physiology GA 608MG UT WOS:000278587800662 ER PT J AU Shiono, H Ogawa, S Matsui, T Niwata, S Okada, T Ito, Y AF Shiono, Hiroyuki Ogawa, Shintaro Matsui, Takuya Niwata, Satoru Okada, Tadashi Ito, Yoichiro TI Preparation of basophils from human peripheral blood by a novel continuous flow-through cell separation method SO JOURNAL OF PHYSIOLOGICAL SCIENCES LA English DT Meeting Abstract C1 [Shiono, Hiroyuki; Ogawa, Shintaro; Matsui, Takuya; Okada, Tadashi] Aichi Med Univ, Dept Physiol Sch Med, Aichi, Japan. [Niwata, Satoru] Kurabo Ind Ltd, Neyagawa, Osaka, Japan. [Ito, Yoichiro] NHLBI, NIH, Bioseparat Technol Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1880-6546 J9 J PHYSIOL SCI JI J. Physiol. Sci. PY 2010 VL 60 SU 1 BP S173 EP S173 PG 1 WC Physiology SC Physiology GA 608MG UT WOS:000278587800577 ER PT J AU Josephson, IR Guia, A Lakatta, EG Lederer, WJ Stern, MD AF Josephson, Ira R. Guia, Antonio Lakatta, Edward G. Lederer, W. Jonathan Stern, Michael D. TI Ca2+-dependent components of inactivation of unitary cardiac L-type Ca2+channels SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CALCIUM-CHANNELS; CA2+ CHANNELS; DEPENDENT INACTIVATION; CA2+-SENSITIVE INACTIVATION; CONDITIONING VOLTAGE; DIVALENT IONS; LOCAL-CONTROL; HEART-CELLS; MODULATION; CALMODULIN AB A Ca2+ ion-dependent inactivation (CDI) of L-type Ca2+ channels (LCC) is vital in limiting and shaping local Ca2+ ion signalling in a variety of excitable cell types. However, under physiological conditions the unitary LCC properties that underlie macroscopic inactivation are unclear. Towards this end, we have probed the gating kinetics of individual cardiac LCCs recorded with a physiological Ca2+ ion concentration (2 mm) permeating the channel, and in the absence of channel agonists. Upon depolarization the ensemble-averaged LCC current decayed with a fast and a slow exponential component. We analysed the unitary behaviour responsible for this biphasic decay by means of a novel kinetic dissection of LCC gating parameters. We found that inactivation was caused by a rapid decrease in the frequency of LCC reopening, and a slower decline in mean open time of the LCC. In contrast, with barium ions permeating the channel ensemble-averaged currents displayed only a single, slow exponential decay and little time dependence of the LCC open time. Our results demonstrate that the fast and slow phases of macroscopic inactivation reflect the distinct time courses for the decline in the frequency of LCC reopening and the open dwell time, both of which are modulated by Ca2+ influx. Analysis of the evolution of CDI in individual LCC episodes was employed to examine the stochastic nature of the underlying molecular switch, and revealed that influx on the order of a thousand Ca2+ ions may be sufficient to trigger CDI. This is the first study to characterize both the unitary kinetics and the stoichiometry of CDI of LCCs with a physiological Ca2+ concentration. These novel findings may provide a basis for understanding the mechanisms regulating unitary LCC gating, which is a pivotal element in the local control of Ca2+-dependent signalling processes. C1 [Josephson, Ira R.] CUNY City Coll, Sch Med, Dept Physiol & Pharmacol, New York, NY 10031 USA. [Josephson, Ira R.; Lederer, W. Jonathan] Univ Maryland, Ctr Med Biotechnol, Inst Biotechnol, Inst Mol Cardiol, Baltimore, MD 21201 USA. [Guia, Antonio; Lakatta, Edward G.; Stern, Michael D.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Josephson, IR (reprint author), CUNY City Coll, Sch Med, Dept Physiol & Pharmacol, 138th St & Convent Ave, New York, NY 10031 USA. EM josephso@med.cuny.edu RI Lederer, William/B-1285-2010 FU NIA/NIH Intramural Research Program; NIH FX We thank Drs Darryl Abernethy, Victor Maltsev and Evgeny Kobrinsky for their comments on the manuscript, and Bruce Ziman for technical support. During which time when the experiments were conducted Dr Josephson was a National Research Council Senior Research Associate. Support was provided by the NIA/NIH Intramural Research Program (E.G.L. and M.D.S.) and extramural NIH grants (W.J.L.). NR 32 TC 3 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2010 VL 588 IS 1 BP 213 EP 223 DI 10.1113/jphysiol.2009.178343 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 540WP UT WOS:000273371600030 PM 19917566 ER PT J AU Niemiec, CP Ryan, RM Patrick, H Deci, EL Williams, GC AF Niemiec, Christopher P. Ryan, Richard M. Patrick, Heather Deci, Edward L. Williams, Geoffrey C. TI The energization of health-behavior change: Examining the associations among autonomous self-regulation, subjective vitality, depressive symptoms, and tobacco abstinence SO JOURNAL OF POSITIVE PSYCHOLOGY LA English DT Article DE depressive symptoms; self-determination theory; tobacco abstinence; vitality ID SMOKING-CESSATION; NEGATIVE AFFECT; NICOTINE DEPENDENCE; MAJOR DEPRESSION; POSITIVE MOOD; SMOKERS; TRIAL; INTERVENTION; ANTECEDENTS; PERSONALITY AB Most research on the psychological correlates of smoking behavior has focused on negative indices of wellness, but findings are mixed, contradictory, controversial, and, thus, inconclusive. This study, guided by self-determination theory, examined both positive (viz., vitality) and negative (viz., depressive symptoms) indices of psychological health as predictors of long-term tobacco abstinence in the context of a randomized clinical trial. It also examined autonomous self-regulation and cigarette use as predictors of psychological health. Results supported the proposed conditional indirect effect model in which change in cigarette use mediated the relation of change in autonomous self-regulation for smoking cessation to change in vitality, and this indirect effect was moderated by treatment condition. Further, change in vitality predicted long-term tobacco abstinence. Results for depressive symptoms were largely null. Discussion focuses on the importance of considering positive indices of psychological health for understanding the psychological correlates of smoking behavior. C1 [Niemiec, Christopher P.; Ryan, Richard M.; Deci, Edward L.; Williams, Geoffrey C.] Univ Rochester, Dept Clin & Social Sci Psychol, New York, NY USA. [Patrick, Heather] NCI, Div Canc Control & Populat Sci, Behav Res Program, Hlth Promot Res Branch, Bethesda, MD 20892 USA. RP Niemiec, CP (reprint author), Univ Rochester, Dept Clin & Social Sci Psychol, New York, NY USA. EM niemiec@psych.rochester.edu OI Ryan, Richard M/0000-0002-2355-6154 NR 51 TC 10 Z9 10 U1 7 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1743-9760 J9 J POSIT PSYCHOL JI J. Posit. Psychol. PY 2010 VL 5 IS 2 BP 122 EP 138 DI 10.1080/17439760903569162 PG 17 WC Psychology, Multidisciplinary SC Psychology GA 778XN UT WOS:000291742800002 ER PT J AU Chen, QR Song, YK Yu, LR Wei, JS Chung, JY Hewitt, SM Veenstra, TD Khan, J AF Chen, Qing-Rong Song, Young K. Yu, Li-Rong Wei, Jun S. Chung, Joon-Yong Hewitt, Stephen M. Veenstra, Timothy D. Khan, Javed TI Global Genomic and Proteomic Analysis Identifies Biological Pathways Related to High-Risk Neuroblastoma SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE neuroblastoma; ICAT; pathway analysis; proteomics; genomics ID CODED AFFINITY TAGS; GENE-EXPRESSION; CELL-ADHESION; N-MYC; DIFFERENTIATION; PROGNOSIS; CANCER; SURVIVAL; STAGE; CADM1 AB Neuroblastoma (NB) is a heterogeneous pediatric tumor. To better understand the biological pathways involved in the development of high-risk neuroblastoma, we performed parallel global protein and mRNA expression profiling on NB tumors of stage 4 MYCN-amplified (4+) and stage 1 MYCN-not-amplified (1-) using isotope-coded affinity tags (ICAT) and Affymetrix U133plus2 microarray, respectively. A total of 1461 proteins represented. by 2 or more peptides were identified from the quantitative ICAT analysis, of which 433 and 130 proteins are up- or down-regulated, respectively, in 4+ tumor compared to the 1- tumor. Pathway analysis of the differentially expressed proteins showed the enrichment of glycolysis, DNA replication and cell cycle processes in the up-regulated proteins and cell adhesion, nervous system development and cell differentiation processes in the down-regulated proteins in 4+ tumor; suggesting a less mature neural and a more invasive phenotype of 4+ tumor. Myc targets and ribosomal proteins are overrepresented in the 4+ tumors as expected; functional gene sets reported to be enriched in neural and embryonic stem cells are significantly enriched in the 4+ tumor, indicating the existence of a sternness signature in MYCN-amplified stage 4 tumor. In addition, protein and mRNA expression are moderately correlated (r=0.51, p < 0.0001), as approximately half of the up-regulated proteins in 4+ tumor have elevated mRNA level (n = 208), and one-third of down-regulated proteins have lower mRNA expression (n = 47). Further biological network analysis revealed that the differentially expressed proteins closely interact with other proteins of known networks; the important role of MYCN is confirmed and other transcription factors identified in the network may have potential roles in the biology of NB tumor. We used global genomic and proteomic analysis to identify biologically relevant proteins and pathways important to NB progression and development that may provide new insights into the biology of advanced neuroblastoma. C1 [Chen, Qing-Rong; Song, Young K.; Wei, Jun S.; Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD 20877 USA. [Chen, Qing-Rong] NCI, Bioinformat Support Grp, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. [Yu, Li-Rong; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Gaithersburg, MD 20877 USA. RP Khan, J (reprint author), NCI, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014; OI Khan, Javed/0000-0002-5858-0488; Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 FU NIH [HHSN261200800001E]; National Cancer Institute, Center for Cancer Research FX We thank Drs. Frank Westermann and Frank Berthold of German Cancer Research Center, Heidelberg (DZNSG), Drs. John Maris, Wendy London of the Children's Oncology Group (COG), Steven QLjalrnan of the Cooperative Human Tissue Network (CHTN) for the tumor samples and patient demographic information. We thank Dr. Thorrias Badgett for his critical reading and helpful comments on the manuscript. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. It has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, cornmercial products, or organizations imply endorsenient by the U.S. Government. This research was supported in part by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. NR 31 TC 22 Z9 23 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JAN PY 2010 VL 9 IS 1 BP 373 EP 382 DI 10.1021/pr900701v PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 539PI UT WOS:000273267900035 PM 19921788 ER PT J AU Nestadt, G Di, CZ Samuels, JF Bienvenu, OJ Reti, IM Costa, P Eaton, WW Bandeen-Roche, K AF Nestadt, Gerald Di, Chongzhi Samuels, J. F. Bienvenu, O. J. Reti, I. M. Costa, P. Eaton, William W. Bandeen-Roche, Karen TI The stability of DSM personality disorders over twelve to eighteen years SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Personality; Personality disorders; Consistency (measurement) ID 2-YEAR STABILITY; FOLLOW-UP; OUTPATIENTS; BORDERLINE; COMMUNITY; SCHIZOTYPAL; BALTIMORE; DIAGNOSIS; AVOIDANT; CRITERIA AB Background: Stability of personality disorders is assumed in most nomenclatures; however, the evidence for this is limited and inconsistent. The aim of this study is to investigate the stability of DSM-III personality disorders in a community sample of eastern Baltimore residents unselected for treatment. Methods: Two hundred ninety four participants were examined on two occasions by psychiatrists using the same standardized examination twelve to eighteen years apart. All the DSM-III criteria for personality disorders were assessed. Item-response analysis was adapted into two approaches to assess the agreement between the personality measures on the two occasions. The first approach estimated stability in the underlying disorder, correcting for error in trait measurement, and the second approach estimated stability in the measured disorder, without correcting for item unreliability. Results: Five of the ten personality disorders exhibited moderate stability in individuals: antisocial, avoidant, borderline, histrionic, and schizotypal. Associated estimated ICCs for stability of underlying disorder over time ranged between approximately 0.4 and 0.7-0.8. A sixth disorder, OCPD, exhibited appreciable stability with estimated ICC of approximately 0.2-0.3. Dependent, narcissistic, paranoid, and schizoid disorders were not demonstrably stable. Conclusions: The findings suggest that six of the DSM personality disorder constructs themselves are stable, but that specific traits within the DSM categories are both of lesser importance than the constructs themselves and require additional specification. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Samuels, J. F.; Bienvenu, O. J.; Reti, I. M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Di, Chongzhi; Bandeen-Roche, Karen] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. [Eaton, William W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD 21287 USA. [Costa, P.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Nestadt, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Meyer 113,600 N Wolfe St, Baltimore, MD 21287 USA. EM gnestadt@jhmi.edu OI Samuels, Jack/0000-0002-6715-7905; Costa, Paul/0000-0003-4375-1712 FU National Institutes of Health [MH50616, MH64543, MH47447]; NIA FX Supported by National Institutes of Health grants MH50616, MH64543 and MH47447 and the Intramural Research Program, NIA. NR 32 TC 6 Z9 6 U1 4 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JAN PY 2010 VL 44 IS 1 BP 1 EP 7 DI 10.1016/j.jpsychires.2009.06.009 PG 7 WC Psychiatry SC Psychiatry GA 555HG UT WOS:000274499100001 PM 19656527 ER PT J AU Coleman-Cowger, VH Erickson, K Spong, CY Portnoy, B Croswell, J Schulkin, J AF Coleman-Cowger, Victoria H. Erickson, Kristine Spong, Catherine Y. Portnoy, Barry Croswell, Jennifer Schulkin, Jay TI Current Practice of Cesarean Delivery on Maternal Request Following the 2006 State-of-the-Science Conference SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE cesarean section; maternal request; State-of-the-Science Conference AB OBJECTIVE: To determine obstetrician-gynecologists' practice patterns of cesarean delivery on maternal request (CDMR) following the 2006 National Institutes Of Health (NIH) State-of-the-Science conference on this topic, and compare them with those in their practice prior to the conference. STUDY DESIGN: Questionnaires were: mailed to 612 American College of Obstetricians and, Gynecologists fellows whoa participated in a 2006 preconference survey, with 59% responding. The survey assessed demographic characteristics, practice, attitudes, knowledge regarding potential risks and benefits, counseling practices, and department policies with regards to CDMR. RESULTS: The majority of obstetrician-gynecologists in our sample continues to believe that a woman has the right to CDMR, but fewer than in 2006 would agree to perform this procedure. In general, obstetrician-gynecologists associate more risks and fewer benefits with CDMR than in 2006. CONCLUSION: Some physicians have shifted their perception of CDMR risks and benefits since the NIH State-of-the-Science conference; however, practice patterns have not changed significantly. (J Reprod Med 2010;55:25-30) C1 Amer Coll Obstricians & Gynecologists, Dept Res, Washington, DC USA. NIH, Mol Imaging Branch, Pregnancy & Perinatol Branch, Off Dis Prevent, Bethesda, MD 20892 USA. NIH, Off Med Applicat Res, Bethesda, MD 20892 USA. RP Coleman-Cowger, VH (reprint author), Chestnut Hlth Syst, 448 Wylie Dr, Normal, IL 61761 USA. EM vhcole-man@chestnut.org OI Coleman-Cowger, Victoria/0000-0002-7745-7223 FU Office of Medical Applications of Research, National Institutes of Health; Maternal and Child Health Bureau (Title V, Social Security Act), Health Resources and Services Administration, Department of Health and Human Services [R60 MC 05674] FX Supported by the Office of Medical Applications of Research, National Institutes of Health, and grant R60 MC 05674 from the Maternal and Child Health Bureau (Title V, Social Security Act), Health Resources and Services Administration, Department of Health and Human Services. NR 5 TC 5 Z9 5 U1 0 U2 0 PU J REPROD MED INC PI ST LOUIS PA 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD JAN-FEB PY 2010 VL 55 IS 1-2 BP 25 EP 30 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 569BS UT WOS:000275571500005 PM 20337204 ER PT J AU Liu, XM Akula, N Skup, M Brotman, MA Leibenluft, E McMahon, FJ AF Liu, Xinmin Akula, Nirmala Skup, Martha Brotman, Melissa A. Leibenluft, Ellen McMahon, Francis J. TI A Genome-Wide Association Study of Amygdala Activation in Youths With and Without Bipolar Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE amygdala; bipolar disorder; DOK5; functional magnetic resonance imaging ID MULTILOCUS GENOTYPE DATA; ENDOPHENOTYPE CONCEPT; FACIAL EXPRESSIONS; GENETIC-VARIATION; IMAGING GENETICS; COMMON DISEASE; RATING-SCALE; SCHIZOPHRENIA; CHILDREN; RELIABILITY AB Objective: Functional magnetic resonance imaging is commonly used to characterize brain activity underlying a variety of psychiatric disorders. A previous functional magnetic resonance imaging study found that amygdala activation during a face-processing task differed between pediatric patients with bipolar disorder (BD) and healthy controls. We undertook a genome-wide association study to explore the genetic architecture of this neuroimaging phenotype. Method: Thirty-nine patients with BD and 29 healthy controls who had previously undergone functional magnetic resonance imaging when viewing a neutral face were genotyped using a genome-wide single-nucleotide polymorphism (SNP) array. After quality control, 104,043 SNPs were tested against normalized amygdala activation scores obtained from the right and left hemispheres. Genetic association was tested with covariates to control for race and ethnicity. Patients and controls were grouped together in the primary analyses. Results: Right amygdala activation under the hostility contrast was most strongly associated with an SNP in the gene DOK5 (rs2023454, p = 4.88 x 10(-7), false discovery rate = 0.05). DOK5 encodes a substrate of tropomyosin-related kinase B/C receptors involved in neurotrophin signaling. This SNP accounted for about 33% of the variance in youths with BD and 12% of the variance in healthy youths. Other results (false discovery rate <50%) were also observed at SNPs near several other genes. Conclusions: To our knowledge, this is the first genome-wide association study of amygdala activation in adolescents with BD. Although preliminary, these data Suggest that DOK5 and perhaps several other genes influence the magnitude of amygdala activation during face processing, particularly in those with BD. Further studies are needed to replicate these findings and characterize the mechanisms involved. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(1):33-41. C1 [Liu, Xinmin; Akula, Nirmala; Skup, Martha; Brotman, Melissa A.; Leibenluft, Ellen; McMahon, Francis J.] NIMH, Bethesda, MD 20892 USA. [Skup, Martha] Yale Univ, New Haven, CT USA. RP Liu, XM (reprint author), 35 Convent Dr,Bldg 35,Room 1A-208, Bethesda, MD 20892 USA. EM liuxinmin@mail.nih.gov RI liu, xinmin/D-7017-2011; Brotman, Melissa/H-7409-2013; OI McMahon, Francis/0000-0002-9469-305X FU National Institute Mental Health at the National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute Mental Health at the National Institutes of Health. NR 54 TC 16 Z9 16 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2010 VL 49 IS 1 BP 33 EP 41 DI 10.1016/j.jaac.2009.10.006 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 548IW UT WOS:000273955800006 PM 20215924 ER PT J AU Hooper, SR Giuliano, AJ Youngstrom, EA Breiger, D Sikich, L Frazier, JA Findling, RL McClellan, J Hamer, RM Vitiello, B Lieberman, JA AF Hooper, Stephen R. Giuliano, Anthony J. Youngstrom, Eric A. Breiger, David Sikich, Linmarie Frazier, Jean A. Findling, Robert L. McClellan, Jon Hamer, Robert M. Vitiello, Benedetto Lieberman, Jeffrey A. TI Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE early-onset schizophrenia; childhood schizophrenia; schizoaffective disorder in childhood; neurocognition in schizophrenia ID SPECTRUM DISORDERS; COGNITIVE FUNCTION; DEFICITS; ADOLESCENTS; DYSFUNCTION; RATIONALE; PSYCHOSIS; ADULTS; TEOSS; CATIE AB Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship of different variables of illness severity and adaptive behavior to neuropsychological functioning. Method: Participants ranged in age from 8 to 19 years. Diagnostic status was confirmed via structured interview over multiple time points. Domains of neuropsychological functioning included fine-motor, attention, working memory, problem-solving efficiency, inhibitory control, and social cognition. Other variables included intelligence (IQ), academic achievement skills, adaptive behavior, and different measures of illness severity. Results: The two groups did not differ on IQ or on any of the neuropsychological domains. The SZ group performed significantly lower in spelling. A high proportion of individuals in both groups reflected significant intellectual and academic achievement skill deficits. Significant correlations were found between the neurocognitive domains and both illness severity and adaptive behavior variables. Conclusions: There were few differences between the SZ and SA groups on IQ, achievement, or neuropsychological functioning; however, both groups showed significantly high rates of deficits in IQ and basic academic skills. Correlations of the neurocognitive functions with illness severity and adaptive behavior were small to moderate in magnitude. These findings continue to implicate the importance of neurocognitive functioning as a key area of vulnerability in the study of youth with schizophrenia spectrum disorders. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(1):52-60. C1 [Hooper, Stephen R.] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Ctr Dev & Learning, Chapel Hill, NC 27599 USA. [Giuliano, Anthony J.; Frazier, Jean A.] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA. [Breiger, David; McClellan, Jon] Univ Washington, Seattle, WA 98195 USA. [Findling, Robert L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Vitiello, Benedetto] NIMH, Bethesda, MD USA. [Lieberman, Jeffrey A.] Columbia Univ, New York, NY 10027 USA. [Lieberman, Jeffrey A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Hooper, SR (reprint author), Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Ctr Dev & Learning, CB 7255, Chapel Hill, NC 27599 USA. EM Stephen.hooper@cdl.unc.edu FU National Institute of Mental Health [U01MH61528, U01MH61464, U01MH62726, U01MH61355]; Maternal Child Health Bureau [MCJ379154A]; Administration on Developmental Disabilities [90DD043003]; Clinical Research Centers at Seattle Children's Hospital, University of Washington [M01-RR-00037]; University of North Carolina [M01-RR00046] FX The Treatment of Early Onset Schizophrenia Spectrum (TEOSS) project was conducted with grant support from the National Institute of Mental Health under cooperative agreements U01MH61528 to the University of North Carolina (P.I,: Lin Sikich), U01MH61464 to the University of Washington (P.I.: Jon McClellan), U01MH62726 to Harvard Medical School (P.I.: Jean Frazier), and U01MH61355 to Case Western Reserve University (P.I.: Robert Findling), and by the Maternal Child Health Bureau (#MCJ379154A), and the Administration on Developmental Disabilities (#90DD043003). The research was conducted in NIH supported Clinical Research Centers at Seattle Children's Hospital, University of Washington (M01-RR-00037) and the University of North Carolina (M01-RR00046). NR 58 TC 19 Z9 21 U1 12 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2010 VL 49 IS 1 BP 52 EP 60 DI 10.1016/j.jaac.2009.11.001 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 548IW UT WOS:000273955800008 PM 20215926 ER PT J AU Cowen, EW Nguyen, JC Miller, DD McShane, D Arron, ST Prose, NS Turner, ML Fox, LP AF Cowen, Edward W. Nguyen, Josephine C. Miller, Daniel D. McShane, Diana Arron, Sarah T. Prose, Neil S. Turner, Maria L. Fox, Lindy P. TI Chronic phototoxicity and aggressive squamous cell carcinoma of the skin in children and adults during treatment with voriconazole SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE fungal infection; immunosuppression; photoaging; photosensitivity; phototoxicity; squamous cell carcinoma; voriconazole ID TRANSPLANT RECIPIENTS; ANTIFUNGAL AGENT; THERAPY; CANCERS; PSEUDOPORPHYRIA; PATIENT AB Background. Voriconazole is a broad-spectrum antifungal agent associated with photosensitivity and accelerated photoaging. A possible link with aggressive squamous cell carcinoma (SCC) has also been reported. Objective: We sought to determine the incidence and frequency of cutaneous SCC among patients undergoing long-term treatment with voriconazole who also manifest features of chronic phototoxicity. Methods: We conducted a retrospective review of patients who developed one or more squamous cell neoplasms during long-term treatment with voriconazole at 3 academic dermatology centers. Results: A total of 51 cutaneous SCC were identified in 8 patients (median age 34.5 years, range 9-54) treated with chronic voriconazole (median duration 46.5 months, range 13-60). Underlying diagnoses included graft-versus-host disease, HIV, and Wegener granulomatosis. Signs of chronic phototoxicity and accelerated photoaging included erythema, actinic keratoses, and lentigo formation. Limitations: The retrospective nature of the study cannot determine the true population risk of SCC associated with voriconazole therapy. A prospective cohort study is needed. Conclusion: A high index of suspicion for photosensitivity and SCC may be warranted with chronic voriconazole use when used in the setting of concurrent immunosuppression. (J Am Acad Dermatol 2010;62:31-7.) C1 [Cowen, Edward W.; Nguyen, Josephine C.; Turner, Maria L.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Miller, Daniel D.; Arron, Sarah T.; Fox, Lindy P.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [McShane, Diana; Prose, Neil S.] Duke Univ, Dept Dermatol, Durham, NC 27706 USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1908,Bldg 10,Room 12N238, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov FU National Institutes of Health, Center for Cancer Research, National Cancer Institute FX Supported in part by the Intramural Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute. NR 25 TC 88 Z9 90 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2010 VL 62 IS 1 BP 31 EP 37 DI 10.1016/j.jaad.2009.09.033 PG 7 WC Dermatology SC Dermatology GA 546BJ UT WOS:000273781800003 PM 19896749 ER PT J AU Anderson, ET Davis, AS Law, JM Lewbart, GA Christian, LS Harms, CA AF Anderson, Eric T. Davis, A. Sally Law, J. McHugh Lewbart, Gregory A. Christian, Larry S. Harms, Craig A. TI Gross and Histologic Evaluation of 5 Suture Materials in the Skin and Subcutaneous Tissue of the California Sea Hare (Aplysia californica) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID ANTIMICROBIAL PEPTIDES; BODY-WALL; ANTIBIOTICS; FISH AB Invertebrates are increasing in their importance to both the public and private aquarium trade and play a vital role in biomedical research. Surgical techniques have become an important approach to obtaining data and maintaining good health in both of these areas. However, studies examining tissue reaction to suture material in invertebrates are lacking. The current study evaluated the gross and histologic reaction of Aplysia californica to 5 commonly used suture materials, including polydioxanone, black braided silk, polyglactin 910, monofilament nylon, and monofilament poliglecaprone. Histologic samples were graded on the amount of edema (score, 1 to 4), inflammation (1 to 4), and granuloma formation (1 to 4) present, and a final overall histology score (1 to 6) was assigned to each sample. Compared with untreated control tissue, all suture materials caused significantly increased tissue reaction, but the overall histology score did not differ among the suture materials. Silk was the only suture that did not have a significantly increased granuloma score when compared with the control. Although none of the suture materials evaluated seemed clearly superior for use in Aplysia, we recommend silk because of its less robust granuloma induction, which is favorable in a clinical and research setting. C1 [Anderson, Eric T.; Lewbart, Gregory A.; Christian, Larry S.; Harms, Craig A.] N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27695 USA. [Davis, A. Sally; Law, J. McHugh] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC 27695 USA. [Anderson, Eric T.; Harms, Craig A.] N Carolina State Univ, Ctr Marine Sci & Technol, Morehead City, NC USA. [Davis, A. Sally] NCI, Comparat Mol Pathol Unit, NIH, Bethesda, MD 20892 USA. RP Harms, CA (reprint author), N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27695 USA. EM craig_harms@ncsu.edu OI Davis, Anne/0000-0001-5711-3936 NR 29 TC 6 Z9 6 U1 1 U2 4 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JAN PY 2010 VL 49 IS 1 BP 64 EP 68 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 550SO UT WOS:000274150100012 PM 20122319 ER PT J AU Thompson, FE Subar, AF Loria, CM Reedy, JL Baranowski, T AF Thompson, Frances E. Subar, Amy F. Loria, Catherine M. Reedy, Jill L. Baranowski, Tom TI Need for Technological Innovation in Dietary Assessment SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID FOOD FREQUENCY QUESTIONNAIRE; EPISODICALLY CONSUMED FOODS; 13-YEAR-OLD CHILDREN; ENERGY-INTAKE; VALIDATION; SYSTEM; RECALL; NUTRIENT; VALIDITY; WOMEN C1 [Thompson, Frances E.; Subar, Amy F.; Reedy, Jill L.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. [Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA. [Baranowski, Tom] ARS, Baylor Coll Med, USDA, Childrens Nutr Res Ctr, Houston, TX USA. RP Thompson, FE (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, 6130 Execut Blvd,EPN 4095A, Bethesda, MD 20892 USA. EM thompsof@mail.nih.gov OI Baranowski, Tom/0000-0002-0653-2222 FU Intramural NIH HHS [Z99 CA999999] NR 53 TC 95 Z9 95 U1 2 U2 38 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2010 VL 110 IS 1 BP 48 EP 51 DI 10.1016/j.jada.2009.10.008 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 587LL UT WOS:000276993800009 PM 20102826 ER PT J AU Subar, AF Crafts, J Zimmerman, TP Wilson, M Mittl, B Islam, NG McNutt, S Potischman, N Buday, R Hull, SG Baranowski, T Guenther, PM Willis, G Tapia, R Thompson, FE AF Subar, Amy F. Crafts, Jennifer Zimmerman, Thea Palmer Wilson, Michael Mittl, Beth Islam, Noemi G. McNutt, Suzanne Potischman, Nancy Buday, Richard Hull, Stephen G. Baranowski, Tom Guenther, Patricia M. Willis, Gordon Tapia, Ramsey Thompson, Frances E. TI Assessment of the Accuracy of Portion Size Reports Using Computer-Based Food Photographs Aids in the Development of an Automated Self-Administered 24-Hour Recall SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DIETARY ASSESSMENT INSTRUMENTS; FREQUENCY QUESTIONNAIRE; YOUNG-ADULTS; VALIDITY; VALIDATION; REPRODUCIBILITY; BEVERAGES; INTERVIEW; CHILDREN; SYSTEM AB Objective To assess the accuracy of portion-size estimates and participant preferences using various presentations of digital images. Design Two observational feeding studies were conducted. In both, each participant selected and consumed foods for breakfast and lunch, buffet style, serving themselves portions of nine foods representing five forms (eg, amorphous, pieces). Serving containers were weighed unobtrusively before and after selection as was plate waste. The next day, participants used a computer software program to select photographs representing portion sizes of foods consumed the previous day. Preference information was also collected. In Study 1 (n=29), participants were presented with four different types of images (aerial photographs, angled photographs, images of mounds, and household measures) and two types of screen presentations (simultaneous images vs an empty plate that filled with images of food portions when clicked). In Study 2 (n=20), images were presented in two ways that varied by size (large vs small) and number (4 vs 8). Subjects/setting Convenience sample of volunteers of varying background in an office setting. Statistical analyses performed Repeated-measures analysis of variance of absolute differences between actual and reported portions sizes by presentation methods. Results Accuracy results were largely not statistically significant, indicating that no one image type was most accurate. Accuracy results indicated the use of eight vs four images was more accurate. Strong participant preferences supported presenting simultaneous vs sequential images. Conclusions These findings support the use of aerial photographs in the automated self-administered 24-hour recall. For some food forms, images of mounds or household measures are as accurate as images of food and, therefore, are a cost-effective alternative to photographs of foods. J Am Diet Assoc. 2010;110:55-64. C1 [Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. [Crafts, Jennifer; Wilson, Michael; Mittl, Beth; Hull, Stephen G.] Westat Corp, Rockville, MD 20850 USA. [Zimmerman, Thea Palmer] Westat Corp, Cleveland, OH USA. [Islam, Noemi G.; Baranowski, Tom] Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. [McNutt, Suzanne] Westat Corp, Salt Lake City, UT USA. [Buday, Richard; Tapia, Ramsey] Archimage, Houston, TX USA. [Guenther, Patricia M.] Ctr Nutr Policy & Promot, USDA, Alexandria, VA USA. RP Subar, AF (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, 6130 Execut Blvd,EPN 4005, Bethesda, MD 20892 USA. EM subara@mail.nih.gov OI Baranowski, Tom/0000-0002-0653-2222 FU National Cancer Institute FX This research was funded by National Cancer Institute contracts awarded to Archimage, Inc, and Westat. NR 35 TC 69 Z9 69 U1 0 U2 19 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2010 VL 110 IS 1 BP 55 EP 64 DI 10.1016/j.jada.2009.10.007 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 587LL UT WOS:000276993800011 PM 20102828 ER PT J AU Baranowski, T Beltran, A Martin, S Watson, KB Islam, N Robertson, S Berno, S Dadabhoy, H Thompson, D Cullen, K Buday, R Subar, AF Baranowski, J AF Baranowski, Tom Beltran, Alicia Martin, Shelby Watson, Kathleen B. Islam, Noemi Robertson, Shay Berno, Stephanie Dadabhoy, Hafza Thompson, Debbe Cullen, Karen Buday, Richard Subar, Amy F. Baranowski, Janice TI Tests of the Accuracy and Speed of Categorizing Foods into Child vs Professional Categories Using Two Methods of Browsing with Children SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID 13-YEAR-OLD CHILDREN AB This research tested whether children could categorize foods more accurately and speedily when presented with child-generated rather than professionally generated food categories, and whether a graphically appealing browse procedure similar to the Apple iTunes (Cupertino, CA) "cover flow" graphical user interface accomplished this better than the more common tree-view structure. In Fall 2008, 104 multiethnic children ages 8 to 13 were recruited at the Baylor College of Medicine (Houston, TX) and randomly assigned to two browse procedures: cover flow (collages of foods in a category) or tree view (food categories in a list). Within each browse condition children categorized the same randomly ordered 26 diverse foods to both child and professionally organized categories (with method randomly sequenced per child). Acceptance of categorization was determined by registered dietitians. Speed of categorization was recorded by the computer. Differences between methods were determined by repeated measures analysis of variance. Younger children (8 to 9 years old) tended to have lower acceptance and longer speeds of categorization. The quickest categorization was obtained with child categories in a tree structure. Computerized dietary reporting by children can use child-generated food categories and tree structures to organize foods for browsing in a hierarchically organized structure to enhance speed of categorization, but not accuracy. A computerized recall may not be appropriate for children 9 years of age or younger. J Am Diet Assoc. 2010;110:91-94. C1 [Baranowski, Tom] Baylor Coll Med, ARS, USDA, Childrens Nutr Res Ctr,Dept Pediat, Houston, TX 77030 USA. [Buday, Richard] Archimage Inc, Houston, TX USA. [Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. RP Baranowski, T (reprint author), Baylor Coll Med, ARS, USDA, Childrens Nutr Res Ctr,Dept Pediat, 1100 Bates St,Room 2038, Houston, TX 77030 USA. EM tbaranow@bcm.tmc.edu OI Baranowski, Tom/0000-0002-0653-2222 FU National Cancer Institute [5 U01 CA130762-02]; USDA/ARS [58-6250-6001] FX This research was primarily funded by a grant from the National Cancer Institute (5 U01 CA130762-02). This work is also a publication of the United States Department of Agriculture/Agricultural Research Service (USDA/ARS) Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, and had been funded in part with federal funds from the USDA/ARS under Cooperative Agreement no. 58-6250-6001. The contents of this publication do not necessarily reflect the views or policies of the US Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement from the US government. NR 11 TC 11 Z9 11 U1 0 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2010 VL 110 IS 1 BP 91 EP 94 DI 10.1016/j.jada.2009.10.006 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 587LL UT WOS:000276993800015 PM 20102832 ER PT J AU Waldstein, SR Wendell, CR Seliger, SL Ferrucci, L Metter, EJ Zonderman, AB AF Waldstein, Shari R. Wendell, Carrington Rice Seliger, Stephen L. Ferrucci, Luigi Metter, E. Jeffrey Zonderman, Alan B. TI Nonsteroidal Anti-Inflammatory Drugs, Aspirin, and Cognitive Function in the Baltimore Longitudinal Study of Aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE NSAIDs; aspirin; cognitive function; neuropsychology ID ALZHEIMERS-DISEASE; CACHE COUNTY; NSAID USE; RISK; DEMENTIA; ANTAGONISTS; POPULATION; PREVENTION; PROTECT; COHORT AB OBJECTIVES To examine the relations between the use of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin and age-related change in multiple domains of cognitive function in community-dwelling individuals without dementia. DESIGN Longitudinal, with measures obtained on one to 18 occasions over up to 45 years. SETTING General community. PARTICIPANTS A volunteer sample of up to 2,300 participants from the Baltimore Longitudinal Study of Aging free of diagnosed dementia. MEASUREMENTS At each visit, reported NSAID or aspirin use (yes/no) and tests of verbal and visual memory, attention, perceptuo-motor speed, confrontation naming, executive function, and mental status. RESULTS Mixed-effects regression models revealed that NSAID use was associated with less prospective decline on the Blessed Information-Memory-Concentration (I-M-C) Test, a mental status test weighted for memory and concentration (P <.001), and Part B of the Trail Making Test, a test of perceptuo-motor speed and mental flexibility (P <.05). In contrast, aspirin use was related to greater prospective decline on the Blessed I-M-C Test (P <.05) and the Benton Visual Retention Test, a test of visual memory (P <.001). CONCLUSION Consistent with studies of incident dementia, NSAID users without dementia displayed less prospective decline in cognitive function, but on only two cognitive measures. In contrast, aspirin use was associated with greater prospective cognitive decline on select measures, potentially reflecting its common use for vascular disease prophylaxis. Effect sizes were small, calling into question clinical significance, although overall public health significance may be meaningful. C1 [Waldstein, Shari R.; Wendell, Carrington Rice] Univ Maryland, Dept Psychol, Baltimore, MD USA. [Waldstein, Shari R.] Univ Maryland, Sch Med, Div Gerontol, Dept Med, Baltimore, MD 21250 USA. [Seliger, Stephen L.] Univ Maryland, Sch Med, Div Nephrol, Dept Med, Baltimore, MD 21250 USA. [Waldstein, Shari R.] Baltimore Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. [Wendell, Carrington Rice; Ferrucci, Luigi; Metter, E. Jeffrey; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Waldstein, SR (reprint author), Univ Maryland, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM waldstei@umbc.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institutes of Health, National Institute on Aging FX Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.; This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 29 TC 13 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2010 VL 58 IS 1 BP 38 EP 43 DI 10.1111/j.1532-5415.2009.02618.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 540DR UT WOS:000273311500006 PM 20122039 ER PT J AU Milaneschi, Y Bandinelli, S Corsi, AM Vazzana, R Patel, KV Ferrucci, L Guralnik, JM AF Milaneschi, Yuri Bandinelli, Stefania Corsi, Anna Maria Vazzana, Rosamaria Patel, Kushang V. Ferrucci, Luigi Guralnik, Jack M. TI Personal Mastery and Lower Body Mobility in Community-Dwelling Older Persons: The Invecchiare in Chianti Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE personal mastery; lower body mobility; physical performance; SPPB ID COPING RESOURCES; SOCIAL SUPPORT; DEPRESSIVE SYMPTOMS; STRESS; HEALTH; INCHIANTI; MORTALITY; ABILITY; DECLINE; SENSE AB OBJECTIVES To test the hypothesis that, in older persons, sense of personal mastery, defined as the extent to which one regards one's life chance as being under one's own control, predicts change in lower extremity performance during a 6-year follow-up. DESIGN Prospective cohort study. SETTING Community based. PARTICIPANTS Six hundred twenty-six participants aged 65 and older. MEASUREMENTS Personal mastery was assessed at baseline using Pearlin's mastery scale. Lower extremity performance was measured at baseline and at 6-year follow-up using the Short Physical Performance Battery (SPPB) of lower extremity function. RESULTS Higher sense of mastery was associated with a significantly less-steep decline in lower extremity performance. Participants in the two lowest quartiles of personal mastery had, respectively, a 2.6 (95% confidence interval (CI)=1.4-5.1, P=.01) and 3.2 (95% CI=1.6-6.6, P=.002) higher risk of experiencing a substantial decline (>= 3 points) in SPPB scores after 6 years as those in the highest quartile. CONCLUSIONS Older individuals with poor sense of personal mastery are at high risk of accelerated lower extremity physical function decline. Whether interventions aimed at improving personal mastery may prevent disability remains unknown. C1 [Milaneschi, Yuri] InCHIANTI Study Grp, Tuscany Hlth Reg Agcy, I-50125 Florence, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Vazzana, Rosamaria] Univ G DAnnunzio, Dept Med & Sci Aging, Lab Clin Epidemiol, Chieti, Italy. [Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Milaneschi, Y (reprint author), InCHIANTI Study Grp, Tuscany Hlth Reg Agcy, Vle Michelangelo 41, I-50125 Florence, Italy. EM yuri.milaneschi@asf.toscana.it FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging (NIA) [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; National Institutes of Health FX Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.; The InCHIANTI Study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (NIA; Contracts 263 MD 9164 and 263 MD 821336); the InCHIANTI follow-up 1 (2001-2003) was funded by the U.S. NIA (Contracts N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI follow-up 2 and 3 studies (2004-2010) were financed by the U.S. NIA (Contract: N01-AG-5-0002); supported in part by the Intramural Research Program of the NIA, National Institutes of Health. NR 30 TC 9 Z9 9 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2010 VL 58 IS 1 BP 98 EP 103 DI 10.1111/j.1532-5415.2009.02611.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 540DR UT WOS:000273311500014 PM 19943832 ER PT J AU Downs, SM van Dyck, PC Rinaldo, P McDonald, C Howell, RR Zuckerman, A Downing, G AF Downs, Stephen M. van Dyck, Peter C. Rinaldo, Piero McDonald, Clement Howell, R. Rodrey Zuckerman, Alan Downing, Gregory TI Improving newborn screening laboratory test ordering and result reporting using health information exchange SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB Capture, coding and communication of newborn screening (NBS) information represent a challenge for public health laboratories, health departments, hospitals, and ambulatory care practices. An increasing number of conditions targeted for screening and the complexity of interpretation contribute to a growing need for integrated information-management strategies. This makes NBS an important test of tools and architecture for electronic health information exchange (HIE) in this convergence of individual patient care and population health activities. For this reason, the American Health Information Community undertook three tasks described in this paper. First, a newborn screening use case was established to facilitate standards harmonization for common terminology and interoperability specifications guiding HIE. Second, newborn screening coding and terminology were developed for integration into electronic HIE activities. Finally, clarification of privacy, security, and clinical laboratory regulatory requirements governing information exchange was provided, serving as a framework to establish pathways for improving screening program timeliness, effectiveness, and efficiency of quality patient care services. C1 [Downs, Stephen M.] Indiana Univ, Sch Med, Childrens Hlth Serv, Res Program, Indianapolis, IN 46202 USA. [van Dyck, Peter C.] Hlth Resources & Serv Adm, Dept Hlth & Human Serv, Washington, DC USA. [Rinaldo, Piero] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [McDonald, Clement] NIH, Dept Hlth & Human Serv, Lister Hill Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. [Howell, R. Rodrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Zuckerman, Alan] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Downing, Gregory] Personalized Hlth Care Initiat, Dept Hlth & Human Serv, Washington, DC USA. RP Downs, SM (reprint author), Indiana Univ, Sch Med, Childrens Hlth Serv, Res Program, Hlth Informat & Translat Sci Bldg,HS 1020,410 W 1, Indianapolis, IN 46202 USA. EM stmdowns@iupui.edu FU Health Resources and Services Administration Maternal and Child Health Bureau [U22MC06969-01-00] FX The authors would like to thank C Coon and C Gardett for assistance in editing the document. SMD's effort was supported by Health Resources and Services Administration Maternal and Child Health Bureau U22MC06969-01-00. NR 19 TC 10 Z9 12 U1 1 U2 7 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN PY 2010 VL 17 IS 1 BP 13 EP 18 DI 10.1197/jamia.M3295 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 538GY UT WOS:000273173800004 PM 20064796 ER PT J AU Mathew, A Eliasziw, M Devereaux, PJ Merino, JG Barnett, HJM Garg, AX AF Mathew, Anna Eliasziw, Michael Devereaux, P. J. Merino, Jose G. Barnett, Henry J. M. Garg, Amit X. CA NASCET Collaborators TI Carotid Endarterectomy Benefits Patients with CKD and Symptomatic High-Grade Stenosis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; RANDOMIZED-TRIAL; CARDIOVASCULAR-DISEASE; SUBGROUP ANALYSES; SERUM CREATININE; RENAL-INSUFFICIENCY; CORONARY-DISEASE; ISCHEMIC-STROKE; RISK; MORTALITY AB Endarterectomy is generally recommended for symptomatic high-grade (70 to 99%) stenosis of the internal carotid artery, but whether this procedure is beneficial among patients with chronic kidney disease (CKD) is unknown. In this re-analysis of data from the North American Symptomatic Carotid Endarterectomy Trial, we included patients with symptomatic stenosis and either stage 3 CKD (n = 524) or preserved kidney function (n = 966; estimated GFR >= 60). For medically treated patients with high-grade stenosis, risk for ipsilateral stroke at 2 yr was significantly higher in patients with CKD than in those with preserved renal function (31.6 versus 19.3%; P = 0.042); carotid endarterectomy significantly reduced this risk by 82 and 51%, respectively. To prevent one ipsilateral stroke, the number needed to treat by endarterectomy was four for patients with CKD and 10 for patients with preserved renal function. Compared with patients with preserved renal function, those with CKD had similar rates of perioperative stroke and death but higher rates of cardiac events. In conclusion, patients with stage 3 CKD and symptomatic high-grade carotid stenosis gain a large benefit in stroke risk reduction after endarterectomy. C1 [Mathew, Anna; Garg, Amit X.] Univ Western Ontario, Div Nephrol, London, ON, Canada. [Barnett, Henry J. M.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. [Barnett, Henry J. M.] Univ Western Ontario, John P Robarts Res Inst, London, ON, Canada. [Garg, Amit X.] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Eliasziw, Michael] Univ Calgary, Dept Med, Dept Community Hlth Sci, Calgary, AB, Canada. [Devereaux, P. J.; Garg, Amit X.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Devereaux, P. J.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Merino, Jose G.] NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. RP Garg, AX (reprint author), London Hlth Sci Ctr, London Kidney Clin Res Unit, Room ELL-101,800 Commissioners Rd E, London, ON N6A 4G5, Canada. EM amit.garg@lhsc.on.ca OI Merino, Jose/0000-0002-6676-0008; Devereaux, P.J./0000-0003-2935-637X FU Physicians Services Incorporated Foundation; National Institute of Neurological Disorders and Stroke [R01-NS-24456]; Alberta Heritage Foundation for Medical Research; Canadian Institutes of Health Research FX This analysis was supported by a research grant from the Physicians Services Incorporated Foundation. The NASCET trial was Supported by grant R01-NS-24456 from the National Institute of Neurological Disorders and Stroke. M.E. was Supported by the Alberta Heritage Foundation for Medical Research, P.J.D. was Supported by a New Investigator Award from the Canadian Institutes of Health Research, and A.X.G. was Supported by a Clinician Scientist Award from the Canadian Institutes of Health Research. NR 41 TC 16 Z9 18 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2010 VL 21 IS 1 BP 145 EP 152 DI 10.1681/ASN.2009030287 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 546BK UT WOS:000273781900022 PM 20007752 ER PT J AU Olney, CA Backus, JEB Klein, LJ AF Olney, Cynthia A. Backus, Joyce E. B. Klein, Lori J. TI Characteristics of project management at institutions sponsoring National Library of Medicine MedlinePlus Go Local SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID SERVICE AB Objectives: Through interviews with the National Library of Medicine's MedlinePlus Go Local collaborators, an evaluation team sought to identify process characteristics that are critical for long-term sustainability of Go Local projects and to describe the impact that Go Local projects have on sponsoring institutions. Methods: Go Local project coordinators (n = 44) at 31 sponsor institutions participated in semi-structured interviews about their experiences developing and maintaining Go Local sites. Interviews were summarized, checked for accuracy by the participating librarians, and analyzed using a general inductive methodology. Results: Institutional factors that support Go Local projects were identified through the interviews, as well as strategies for staffing and partnerships with external organizations. Positive outcomes for sponsoring institutions also were identified. Conclusions: The findings may influence the National Library of Medicine team's decisions about improvements to its Go Local system and the support it provides to sponsoring institutions. The findings may benefit current sponsoring institutions as well as those considering or planning a Go Local project. C1 [Olney, Cynthia A.] CO Evaluat Consulting, Roswell, GA 30076 USA. [Klein, Lori J.] Natl Lib Med, Reference & Web Serv Sect, Bethesda, MD 20894 USA. RP Olney, CA (reprint author), CO Evaluat Consulting, POB 767671, Roswell, GA 30076 USA. EM olneyc@coevaluation.com; backusj@nlm.nih.gov; klein1@nlm.nih.gov RI Santos, Fernando/H-3257-2011 NR 10 TC 0 Z9 1 U1 0 U2 9 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2010 VL 98 IS 1 BP 65 EP 72 DI 10.3163/1536-5050.98.1.018 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA 548IB UT WOS:000273952700018 PM 20098657 ER PT J AU Zeno, SA Kim-Dorner, SJ Deuster, PA Davis, JL Remaley, AT Poth, M AF Zeno, Stacey A. Kim-Dorner, Su-Jong Deuster, Patricia A. Davis, Jennifer L. Remaley, Alan T. Poth, Merrily TI Cardiovascular Fitness and Risk Factors of Healthy African Americans and Caucasians SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE cardiovascular; C-reactive protein; exercise; cholesterol ID C-REACTIVE PROTEIN; BLOOD LIPID RESPONSE; METABOLIC SYNDROME; CARDIORESPIRATORY FITNESS; PHYSICAL-ACTIVITY; AEROBIC FITNESS; INSULIN-RESISTANCE; WOMENS AWARENESS; HERITAGE FAMILY; HEART-DISEASE AB Background: African Americans have a higher prevalence of and mortality rates from cardiovascular disease than Caucasians. One important risk factor for cardiovascular disease is poor cardiovascular fitness. We quantified associations between fitness and related primary risk factors for cardiovascular disease in healthy African Americans and Caucasians. Methods and Results: Participants included African American (n = 91) and Caucasian (n = 51) men and women aged 18 to 45 years with a body mass index less than 38 kg/m(2), fasting blood glucose less than 126 mg/dL, and blood pressure less than 140/90 mm Hg. Fitness, waist and hip circumference, percent body fat, fasting blood glucose, insulin, lipid profiles, and C-reactive protein (CRP) were measured. The majority of African Americans (57.1%) were low-fair fitness (Caucasians, 31.4%), and only 20.8% were good/high fitness (Caucasians, 39.2%). The number of cardiovascular disease risk factors increased with decreasing fitness, and CRP was negatively associated with fitness in both groups. Conclusions: Low fitness may characterize apparently healthy African Americans as at risk for cardiovascular disease. Including fitness as a risk factor may improve early identification of at-risk African Americans. Importantly, prescribing exercise as medicine and promoting regular physical activity to improve fitness is essential among African Americans. C1 [Kim-Dorner, Su-Jong; Deuster, Patricia A.; Davis, Jennifer L.] Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. [Poth, Merrily] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Remaley, Alan T.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Zeno, SA (reprint author), 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM szeno@usuhs.mil RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 FU US Army Medical Research and Materiel Command, Fort Detrick, Maryland; Peer Reviewed Medical Research Program [DAMD 17-03-2-0024] FX Funding for this project was provided by US Army Medical Research and Materiel Command, Fort Detrick, Maryland, Peer Reviewed Medical Research Program Award (DAMD 17-03-2-0024). NR 41 TC 10 Z9 10 U1 0 U2 3 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JAN PY 2010 VL 102 IS 1 BP 28 EP 35 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 547HX UT WOS:000273878800004 PM 20158133 ER PT J AU Dickersin, K Fredman, L Flegal, KM Scott, J Crawley, B AF Dickersin, Kay Fredman, Lisa Flegal, Katherine M. Scott, Jane Crawley, Barbara TI Female editorship is an important indicator of gender imbalance SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Letter ID EDITORIAL-BOARDS; WOMEN; JOURNALS C1 [Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Fredman, Lisa] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Flegal, Katherine M.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Scott, Jane] NHLBI, NIH, Bethesda, MD 20892 USA. [Crawley, Barbara] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. RP Dickersin, K (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. EM kdickers@jhsph.edu RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 6 TC 2 Z9 2 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD JAN PY 2010 VL 103 IS 1 BP 5 EP 5 DI 10.1258/jrsm.2009.09k071 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 550XZ UT WOS:000274169100002 PM 20056662 ER PT J AU Ning, J Qin, J Shen, Y AF Ning, Jing Qin, Jing Shen, Yu TI Non-parametric tests for right-censored data with biased sampling SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Dependent censoring; Left truncation; Length-biased sampling; Log-rank test; Permutation test; Prevalent cohort; Score test ID PREVALENT COHORT; SURVIVAL-DATA; LENGTH-BIAS; TRUNCATED DATA; LOG-RANK; DURATION; TIMES; UNEMPLOYMENT; STATIONARITY; PREGNANCY AB Testing the equality of two survival distributions can be difficult in a prevalent cohort study when non-random sampling of subjects is involved. Owing to the biased sampling scheme, the independent censoring assumption is often violated. Although the issues about biased inference caused by length-biased sampling have been widely recognized in the statistical, epidemiological and economical literature, there is no satisfactory solution for efficient two-sample testing. We propose an asymptotic most efficient non-parametric test by properly adjusting for length-biased sampling. The test statistic is derived from a full likelihood function and can be generalized from the two-sample test to a k-sample test. The asymptotic properties of the test statistic under the null hypothesis are derived by using its asymptotic independent and identically distributed representation. We conduct extensive Monte Carlo simulations to evaluate the performance of the test statistics proposed and compare them with the conditional test and the standard log-rank test for various biased sampling schemes and right-censoring mechanisms. For length-biased data, empirical studies demonstrated that the test proposed is substantially more powerful than the existing methods. For general left-truncated data, the test proposed is robust, still maintains accurate control of the type I error rate and is also more powerful than the existing methods, if the truncation patterns and right censoring patterns are the same between the groups. We illustrate the methods by using two real data examples. C1 [Ning, Jing] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Div Biostat, Houston, TX 77030 USA. [Qin, Jing] NIAID, Bethesda, MD 20892 USA. [Shen, Yu] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Ning, J (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Div Biostat, 1200 Herman Pressler Dr, Houston, TX 77030 USA. EM jing.ning@uth.tmc.edu FU National Health Research and Development Program of Health Canada [6606-3954-MC]; Pfizer Canada Incorporated through Medical Research Council; National Health Research and Development Program [6603-1417-302(R)]; Bayer Incorporated; British Columbia Health Research Foundation [38 (93-2), 34 (96-1)]; National Institutes of Health [CA79466] FX The authors are grateful to two referees, an Associate Editor and the Joint Editor for their insightful comments on this manuscript. We thank Professor Masoud Asgharian and the investigators from the CSHA for kind use of the dementia data from the CSHA. The data that are reported in the example were collected as part of the CHSA. The core study was funded by the Seniors' Independence Research Program, through the National Health Research and Development Program of Health Canada (project 6606-3954-MC(S)). Additional funding was provided by Pfizer Canada Incorporated through the Medical Research Council-Pharmaceutical Manufacturers Association of Canada Health Activity Program, National Health Research and Development Program project 6603-1417-302(R), Bayer Incorporated and British Columbia Health Research Foundation projects 38 (93-2) and 34 (96-1). The study was co-ordinated through the University of Ottawa and the Division of Aging and Seniors, Health Canada. This research was partially supported by US grant CA79466 from the National Institutes of Health. NR 46 TC 8 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1369-7412 J9 J R STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2010 VL 72 BP 609 EP 630 DI 10.1111/j.1467-9868.2010.00742.x PN 5 PG 22 WC Statistics & Probability SC Mathematics GA 663HY UT WOS:000282875200002 PM 21031144 ER PT J AU Follmann, D Qin, J Hoshino, Y AF Follmann, Dean Qin, Jing Hoshino, Yo TI Estimation of viral infection and replication in cells by using convolution models SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Assays; Deconvolution; Mixture model; Robust methods; Stopped sum ID HERPES-SIMPLEX-VIRUS; CORRELATE; GANGLIA; NUMBER; LOAD AB In some assays, a diluted suspension of infected cells is plated onto multiple wells. In each well the number of genome copies of virus, Y, is recorded, but interest focuses on the number of infected cells, X, and the number of genome copies in the infected cells, W-1,...,W-X. The statistical problem is to recover the distribution or at least moments of X and W on the basis of the convolution Y. We evaluate various parametric statistical models for this 'mixture'- type problem and settle on a flexible robust approach where X follows a two-component Poisson mixture model and W is a shifted negative binomial distribution. Data analysis and simulations reveal that the means and occasionally variances of X and W can be reliably captured by the model proposed. We also identify the importance of selecting an appropriate dilution for a reliable assay. C1 [Follmann, Dean] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Follmann, D (reprint author), NIAID, Biostat Res Branch, 6700A Rockledge Dr, Bethesda, MD 20892 USA. EM dfollmann@niaid.nih.gov NR 18 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0035-9254 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2010 VL 59 BP 423 EP 435 PN 3 PG 13 WC Statistics & Probability SC Mathematics GA 581DD UT WOS:000276500600003 ER PT J AU Detterbeck, F Giaccone, G Loehrer, P Suster, S Wright, C AF Detterbeck, Frank Giaccone, Giuseppe Loehrer, Patrick Suster, Saul Wright, Cameron TI International Thymic Malignancy Interest Group SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material ID EVIDENCE-BASED PATHOLOGY; THYMOMAS C1 [Detterbeck, Frank] Yale Univ, Sch Med, Dept Surg, Div Thorac Surg, New Haven, CT 06520 USA. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Dept Med, Bethesda, MD 20892 USA. [Loehrer, Patrick] Indiana Univ Sch Med, Dept Med, Div Med Oncol, IU Simon Canc Ctr, Indianapolis, IN USA. [Suster, Saul] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. [Wright, Cameron] Harvard Univ, Sch Med, Dept Surg, Mass Gen Hosp Canc Ctr,Div Cardiothorac Surg, Boston, MA 02115 USA. RP Detterbeck, F (reprint author), Yale Univ, Sch Med, Dept Surg, Div Thorac Surg, 333 Cedar St,BB 205, New Haven, CT 06520 USA. EM frank.detterbeck@yale.edu RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 4 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JAN PY 2010 VL 5 IS 1 BP 1 EP 2 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 542LX UT WOS:000273496000001 PM 20035184 ER PT J AU Maher, SA Mauck, RL Rackwitz, L Tuan, RS AF Maher, S. A. Mauck, R. L. Rackwitz, L. Tuan, R. S. TI A nanofibrous cell-seeded hydrogel promotes integration in a cartilage gap model SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Article DE nanofibrous hydrogel; chondrocytes; cartilage repair; TGF beta 3; tissue engineering ID ASSEMBLING PEPTIDE HYDROGEL; ARTICULAR-CARTILAGE; IN-VITRO; REPAIR; ADHESIVE; CHONDROCYTES; DEGRADATION; MATURATION; DEPOSITION; SURFACE AB The presence of a defect in mature articular cartilage can lead to degenerative changes of the joint. This is in part caused by the inability of cartilage to regenerate tissue that is capable of spanning a fissure or crack. In this study, we hypothesized that introduction of a biodegradable cell-seeded nanofibrous hydrogel, Puramatrix (TM), into a cartilage gap would facilitate the generation of a mechanically stable interface. The effects of chondrocyte incorporation within the hydrogel and supplementation with transforming growth factor-beta 3 (TGF beta 3), a known regulator of cell growth and differentiation, on cartilage integration were examined mechanically and histologically as a function of cell density and incubation time. When supplemented with TGF beta 3, the cell-seeded hydrogel exhibited abundant matrix generation within the hydrogel and a corresponding increase in maximum push-out stress as compared to all other groups. Furthermore, initial cell seeding density affected interfacial strength in a time-dependent manner. This study suggests that a cell-seeded TGF beta 3-supplemented hydrogel can encourage integration between two opposing pieces of articular cartilage. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Maher, S. A.] Hosp Special Surg, New York, NY 10021 USA. [Mauck, R. L.; Rackwitz, L.; Tuan, R. S.] NIAMSD, Cartilage Biol & Orthoped Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Maher, SA (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM mahers@hss.edu FU Leo Rosner Foundation; NIAMS; NIH [ZO1 AR41131] FX The authors would like to thank the Hospital for Special Surgery and the Leo Rosner Foundation for funding this study, and are grateful for the support of the intramural Research Program of the NIAMS, NIH (ZO1 AR41131). NR 32 TC 23 Z9 23 U1 2 U2 14 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1932-6254 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD JAN PY 2010 VL 4 IS 1 BP 25 EP 29 DI 10.1002/term.205 PG 5 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA 542MQ UT WOS:000273498100003 PM 19834956 ER PT J AU Slager, RE Simpson, SL LeVan, TD Poole, JA Sandler, DP Hoppin, JA AF Slager, Rebecca E. Simpson, Sean L. LeVan, Tricia D. Poole, Jill A. Sandler, Dale P. Hoppin, Jane A. TI Rhinitis Associated with Pesticide Use Among Private Pesticide Applicators in the Agricultural Health Study SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID RESPIRATORY SYMPTOMS; ALLERGIC RHINITIS; OCCUPATIONAL RHINITIS; ANIMAL CONFINEMENT; DUST EXPOSURE; RISK-FACTORS; ADULT-ONSET; FARMERS; ILLNESS; ASTHMA AB Farmers commonly experience rhinitis but the risk factors are not well characterized. The aim of this study was to analyze cross-sectional data on rhinitis in the past year and pesticide use from 21,958 Iowa and North Carolina farmers in the Agricultural Health Study, enrolled 1993-1997, to evaluate pesticide predictors of rhinitis. Polytomous and logistic regression models were used to assess association between pesticide use and rhinitis while controlling for demographics and farm-related exposures. Sixty-seven percent of farmers reported current rhinitis and 39% reported 3 or more rhinitis episodes. The herbicides glyphosate [odds ratio (OR) = 1.09, 95% confidence interval (95% CI) = 1.05-1.13] and petroleum oil (OR = 1.12, 95% CI = 1.05-1.19) were associated with current rhinitis and increased rhinitis episodes. Of the insecticides, four organophosphates (chlorpyrifos, diazinon, dichlorvos, and malathion), carbaryl, and use of permethrin on animals were predictors of current rhinitis. Diazinon was significant in the overall polytomous model and was associated with an elevated OR of 13+ rhinitis episodes (13+ episodes OR = 1.23, 95% CI = 1.09-1.38). The fungicide captan was also a significant predictor of rhinitis. Use of petroleum oil, use of malathion, use of permethrin, and use of the herbicide metolachlor were significant in exposure-response polytomous models. Specific pesticides may contribute to rhinitis in farmers; agricultural activities did not explain these findings. C1 [Sandler, Dale P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Slager, Rebecca E.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27109 USA. [Simpson, Sean L.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. [LeVan, Tricia D.; Poole, Jill A.] Univ Nebraska, Med Ctr, Dept Med, Pulm Crit Care Sleep & Allergy Div, Omaha, NE 68105 USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services [Z01-CP010119]; National Institutes of Health and National Heart, Lung, and Blood Institute at the Wake Forest University School of Medicine [K12 HL89992] FX This work is supported by intramural research funds (for the AHS) from the National Institute of Environmental Health Sciences (Z01-ES049030) and the National Cancer Institute (Z01-CP010119), National Institutes of Health, U.S. Department of Health and Human Services. RES is supported by the National Institutes of Health and National Heart, Lung, and Blood Institute K12 Scholars' Program in the Genetics and Genomics of Lung Disease, Principal Investigator Deborah A. Meyers, PhD (K12 HL89992), at the Wake Forest University School of Medicine. We thank Stuart Long for preparation of the AHS data set. NR 33 TC 14 Z9 15 U1 2 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2010 VL 73 IS 20 BP 1382 EP 1393 AR PII 926545975 DI 10.1080/15287394.2010.497443 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 647GM UT WOS:000281606400004 PM 20818537 ER PT J AU Brooke, BS Arnaoutakis, G McDonnell, NB Black, JH AF Brooke, Benjamin S. Arnaoutakis, George McDonnell, Nazli B. Black, James H., III TI Contemporary management of vascular complications associated with Ehlers-Danlos syndrome SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 63rd Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY JUN 11-14, 2009 CL Denver, CO SP Soc Vasc Surg (SVS) ID SYNDROME TYPE-IV; GENETIC FEATURES; PATIENT; DISEASE; HETEROGENEITY; PERFORATION; COLLAGEN; REPAIR AB Objectives: There has been debate regarding the safety of performing elective procedures in patients with vascular manifestations associated with Ehlers-Danlos syndrome (EDS). The purpose of this stud), was to review the surgical management and clinical outcomes of EDS patients undergoing vascular procedures at a tertiary medical center with multimodality expertise in connective tissue disorders. Methods. All patients with EDS undergoing endovascular and open vascular procedures at a single-institution academic medical center from 1994 to 2009 were retrospectively reviewed. Clinical data were evaluated including patient demographics, length of stay (LOS), and mortality outcomes during hospital course and long-term follow-up. Results: A total of 40 patients with EDS were identified, including individuals diagnosed with classic (n = 15), hypermobility (n = 16), and vascular (n = 9) types of EDS. These patients collectively underwent 45 endovascular and 18 open procedures for vascular disease during the time period, including embolization (n = 37), angioplasty (n = 8), arterial bypass (n = 5), and aortic aneurysm repair (n = 13). All cases were performed electively, except for one (2%) urgent endovascular and one (5%) emergent open procedure. Endovascular procedures were associated with a median LOS (interquartile range [IQR]) of 2 (1 to 3) days with no procedure-related mortality or in-hospital deaths among all EDS types, whereas open vascular procedures had median LOS (IQR) of 6 (5 to 8) days with one (6%) in-hospital death occurring in a vascular EDS patient. Survival free of any complication at 5 years was 85% and 54% following endovascular and open procedures, respectively. Conclusions. The elective surgical management of vascular disorders in EDS patients using open and endovascular procedures has been associated with good outcomes. Our results suggest that vascular interventions in these EDS patients can be safely performed and should not be withheld until rupture or acute symptoms arise. (J Vasc Surg 2010;51:131-9.) C1 [Brooke, Benjamin S.; Arnaoutakis, George; Black, James H., III] Johns Hopkins Univ Hosp, Div Vasc & Endovasc Surg, Baltimore, MD 21287 USA. [McDonnell, Nazli B.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Black, JH (reprint author), Johns Hopkins Univ Hosp, Div Vasc & Endovasc Surg, Baltimore, MD 21287 USA. EM jhblack@jhmi.edu NR 22 TC 35 Z9 35 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2010 VL 51 IS 1 BP 131 EP 139 DI 10.1016/j.jvs.2009.08.019 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 545BX UT WOS:000273708500024 PM 19879095 ER PT J AU Sahora, A Khanna, C AF Sahora, A. Khanna, C. TI A Survey of Evidence in the Journal of Veterinary Internal Medicine Oncology Manuscripts from 1999 to 2007 SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Article DE Clinical trials; Evidence-based medicine; Statistics ID REMAINS AB Objectives To survey and monitor trends in evidence for oncology manuscripts published in the Journal of Veterinary Internal Medicine (JVIM) between 1999 and 2007 based on an evidence-based medicine (EBM) standard. Methods All veterinary oncology-related articles published in JVIM and 7 other high-impact journals from 1999 to 2007 were collected by database searches. Relevant manuscripts then were characterized including investigator affiliation, subject matter investigated, retrospective or prospective study design, manuscript type, and classifications of manuscripts using an EBM standard. Results A total of 172 relevant veterinary oncology manuscripts were identified in JVIM between 1999 and 2007. The proportion of oncology manuscripts published each year rose with the total number of manuscripts published in JVIM (mean, 13%; range, 8-15%). The author affiliations and subject matter were similar during this evaluation period. Case series represented the most common manuscript type (40%). With the exception of a progressive increase in prospective manuscripts and a reduction in case reports, no significant changes in the classification of manuscripts using EBM standards were seen. During this same period, veterinary oncology manuscripts published in 7 high-impact journals were associated with higher standards of evidence including prospective studies and randomized trials. Conclusions The standards of evidence for veterinary oncology manuscripts published in JVIM have remained static between 1999 and 2007. This survey provides an informative benchmark for the state of evidence in previous JVIM oncology manuscripts and may be useful in identifying specific opportunities that may raise the standards of evidence in future publications in JVIM. C1 [Khanna, C.] NCI, Comparat Oncol Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sahora, A.] Anim Clin Invest LLC, Washington, DC USA. RP Khanna, C (reprint author), NCI, Comparat Oncol Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov NR 10 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD JAN-FEB PY 2010 VL 24 IS 1 BP 51 EP 56 DI 10.1111/j.1939-1676.2009.0394.x PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 540EX UT WOS:000273315100012 PM 19780934 ER PT J AU Henderson, WA Shankar, R Gill, JM Kim, KH Ghany, MG Skanderson, M Butt, AA AF Henderson, Wendy A. Shankar, Ravi Gill, Jessica M. Kim, Kevin H. Ghany, Marc G. Skanderson, Melissa Butt, Adeel A. TI Hepatitis C progressing to hepatocellular carcinoma: the HCV dialysis patient in dilemma SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE co-morbidity; dialysis; end stage renal disease; hepatitis C; hepatocellular carcinoma ID CHRONIC-HEMODIALYSIS PATIENTS; HIV-INFECTED VETERANS; VIRUS-INFECTION; UNITED-STATES; RISK; COINFECTION; CIRRHOSIS; IMPACT; COMORBIDITIES; SURVIVAL AB Approximately 3.2 million people in the United States have chronic hepatitis C virus (HCV) infection; the primary cause for adult liver transplantation and a significant burden on healthcare resources. The role of HCV and other risk factors in development of HCC in patients with chronic kidney disease is not well defined. We studied predictors of hepatocellular carcinoma (HCC) in dialysis patients with chronic HCV by analyzing factors associated with its development. Data were extracted from the United States Renal Database System (USRDS) using ICD-9 codes. Variables included were gender, race, duration on dialysis and co-morbidities (alcohol abuse, drug abuse, HIV, hepatitis B, diabetes and/or presence of cirrhosis). Among the 32 806 HCV infected subjects, 262 cases had HCC. HCC was 12 times more likely in subjects with cirrhosis (P < 0.001), three times more likely in subjects with alcohol abuse (P < 0.001), and 1.3 times more likely in subjects with diabetes (P = 0.04). Asians were three times more likely (P < 0.001) to have HCC. Females were less likely to have HCC compared to males (P = 0.002). The likelihood of having HCC increased with age (P = 0.001). This population-based study demonstrates that among subjects with HCV on dialysis, those with cirrhosis, Asian race and history of alcohol abuse are at highest risk for development of HCC. Furthermore, these findings indicate links between HCV and HCC which are valuable in case management for identifying; monitoring, and managing dialysis patients with HCC. C1 [Henderson, Wendy A.] NINR, Symptoms Management Branch, Biobehav Unit, NIH, Bethesda, MD 20892 USA. [Kim, Kevin H.] Univ Pittsburgh, Sch Educ, Pittsburgh, PA 15260 USA. [Ghany, Marc G.] NIDDK, NIH, Bethesda, MD USA. [Skanderson, Melissa] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Henderson, WA (reprint author), NINR, Symptoms Management Branch, Biobehav Unit, NIH, 10 Ctr Dr,2-1339, Bethesda, MD 20892 USA. EM hendersw@mail.nih.gov OI Henderson, Wendy/0000-0003-3924-7118 FU National Institutes of Health [NIH, 1TL1 RR024155-01, NIH/NIDA, DA016175-01A1]; University of Pittsburgh School of Nursing; Educational Innovation Fund; Duquesne University School of Nursing FX Support was provided by the Symptoms Management Branch, Intramural Research Program, National Institute of Nursing Research, National Institutes of Health. Additional support was provided by the following: Clinical & Translational Science Institute Fellowship (Henderson): NIH, 1TL1 RR024155-01(Reis), NIH/NIDA, DA016175-01A1, (Butt); University of Pittsburgh School of Nursing, Educational Innovation Fund; Duquesne University School of Nursing, Dean's Fund (Henderson). Special thanks to Drs. Thelma Patrick and Mary Ann Thurkettle for their assistance with the pilot phase of this study. NR 28 TC 13 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JAN PY 2010 VL 17 IS 1 BP 59 EP 64 DI 10.1111/j.1365-2893.2009.01151.x PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 545KT UT WOS:000273731700007 PM 19566787 ER PT J AU Krishnan, L Matreyek, KA Oztop, I Lee, K Tipper, CH Li, X Dar, MJ KewalRamani, VN Engelman, A AF Krishnan, Lavanya Matreyek, Kenneth A. Oztop, Ilker Lee, Kyeongeun Tipper, Christopher H. Li, Xiang Dar, Mohd J. KewalRamani, Vineet N. Engelman, Alan TI The Requirement for Cellular Transportin 3 (TNPO3 or TRN-SR2) during Infection Maps to Human Immunodeficiency Virus Type 1 Capsid and Not Integrase SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; REVERSE TRANSCRIPTION COMPLEXES; NUCLEAR IMPORT RECEPTOR; NONDIVIDING CELLS; GENE-TRANSFER; HIV-1 INFECTION; ANEMIA-VIRUS; PREINTEGRATION COMPLEXES; RETROVIRAL VECTORS; LENTIVIRAL VECTOR AB Recent genome-wide screens have highlighted an important role for transportin 3 in human immunodeficiency virus type 1 (HIV-1) infection and preintegration complex (PIC) nuclear import. Moreover, HIV-1 integrase interacted with recombinant transportin 3 protein under conditions whereby Moloney murine leukemia virus (MLV) integrase failed to do so, suggesting that integrase-transportin 3 interactions might underscore active retroviral PIC nuclear import. Here we correlate infectivity defects in transportin 3 knockdown cells with in vitro protein binding affinities for an expanded set of retroviruses that include simian immunodeficiency virus (SIV), bovine immunodeficiency virus (BIV), equine infectious anemia virus (EIAV), feline immunodeficiency virus (FIV), and Rous sarcoma virus (RSV) to critically address the role of integrase-transportin 3 interactions in viral infection. Lentiviruses, with the exception of FIV, display a requirement for transportin 3 in comparison to MLV and RSV, yielding an infection-based dependency ranking of SIV > HIV-1 > BIV and EIAV > MLV, RSV, and FIV. In vitro pulldown and surface plasmon resonance assays, in contrast, define a notably different integrase-transportin 3 binding hierarchy: FIV, HIV-1, and BIV > SIV and MLV > EIAV. Our results therefore fail to support a critical role for integrase binding in dictating transportin 3 dependency during retrovirus infection. In addition to integrase, capsid has been highlighted as a retroviral nuclear import determinant. Accordingly, MLV/HIV-1 chimera viruses pinpoint the genetic determinant of sensitization to transportin 3 knockdown to the HIV-1 capsid protein. We therefore conclude that capsid, not integrase, is the dominant viral factor that dictates transportin 3 dependency during HIV-1 infection. C1 [Krishnan, Lavanya; Matreyek, Kenneth A.; Oztop, Ilker; Tipper, Christopher H.; Li, Xiang; Dar, Mohd J.; Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Krishnan, Lavanya; Matreyek, Kenneth A.; Oztop, Ilker; Tipper, Christopher H.; Li, Xiang; Dar, Mohd J.; Engelman, Alan] Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. [Lee, Kyeongeun; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,CLSB-1010, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu RI Li, Xiang/C-4588-2011; OI Matreyek, Kenneth/0000-0001-9149-551X FU HIV Drug Resistance Program; NIH [AI052014]; Harvard University Center for AIDS Research [P30AI060354]; NIH FX This work was supported by the HIV Drug Resistance Program (V.N.K.), NIH grant AI052014 (A. E.), and the Harvard University Center for AIDS Research, an NIH-funded program (grant P30AI060354), which is supported by the following NIH institutes and centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, and NCCAM. NR 55 TC 100 Z9 101 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2010 VL 84 IS 1 BP 397 EP 406 DI 10.1128/JVI.01899-09 PG 10 WC Virology SC Virology GA 530BQ UT WOS:000272564300038 PM 19846519 ER PT J AU Sekhar, V Reed, SC McBride, AA AF Sekhar, Vandana Reed, Shawna C. McBride, Alison A. TI Interaction of the Betapapillomavirus E2 Tethering Protein with Mitotic Chromosomes SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; TRANSCRIPTION FACTOR HUBF; NUCLEAR ANTIGEN 1; RNA-POLYMERASE-I; BOVINE PAPILLOMAVIRUS; DNA-BINDING; GENE-EXPRESSION; SPLICING FACTORS; COPY NUMBER AB During persistent papillomavirus infection, the viral E2 protein tethers the viral genome to the host cell chromosomes, ensuring maintenance and segregation of the viral genome during cell division. However, E2 proteins from different papillomaviruses interact with distinct chromosomal regions and targets. The tethering mechanism has been best characterized for bovine papillomavirus type 1 (BPV1), where the E2 protein tethers the viral genome to mitotic chromosomes in complex with the cellular bromodomain protein, Brd4. In contrast, the betapapillomavirus human papillomavirus type 8 (HPV8) E2 protein binds to the repeated ribosomal DNA genes that are found on the short arm of human acrocentric chromosomes. In this study, we show that a short 16-amino-acid peptide from the hinge region and the C-terminal DNA binding domain of HPV8 E2 are necessary and sufficient for interaction with mitotic chromosomes. This 16-amino-acid region contains an RXXS motif that is highly conserved among betapapillomaviruses, and both arginine 250 and serine 253 residues within this motif are required for mitotic chromosome binding. The HPV8 E2 proteins are highly phosphorylated, and serine 253 is a site of phosphorylation. The HPV8 E2 chromosome binding sequence also has sequence similarity with chromosome binding regions in the gammaherpesvirus EBNA and LANA tethering proteins. C1 [Sekhar, Vandana; Reed, Shawna C.; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0455, Bethesda, MD 20892 USA. EM amcbride@nih.gov OI McBride, Alison/0000-0001-5607-5157 FU NIAID; NIH FX We thank Moon Kyoo Jang, Atasi Poddar, Sandra Chapman, and Nozomi Sakakibara for critical readings of the manuscript. NR 59 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2010 VL 84 IS 1 BP 543 EP 557 DI 10.1128/JVI.01908-09 PG 15 WC Virology SC Virology GA 530BQ UT WOS:000272564300051 PM 19846509 ER PT J AU DeFilippis, VR Alvarado, D Sali, T Rothenburg, S Fruh, K AF DeFilippis, Victor R. Alvarado, David Sali, Tina Rothenburg, Stefan Frueh, Klaus TI Human Cytomegalovirus Induces the Interferon Response via the DNA Sensor ZBP1 SO JOURNAL OF VIROLOGY LA English DT Article ID INNATE IMMUNE-RESPONSE; ANTIVIRAL SIGNALING PROTEIN; VIRUS PARTICLE ENTRY; DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTOR-9; HEPATITIS-C VIRUS; NF-KAPPA-B; RIG-I; REGULATORY FACTOR-3; GENE-EXPRESSION AB Human cytomegalovirus (HCMV) is a member of the betaherpesvirus family that, unlike other herpesviruses, triggers a strong innate immune response in infected cells that includes transcription of the beta interferon gene via activation of interferon regulatory factor 3 (IRF3). IRF3 activation requires signaling from pattern recognition receptors that is initiated by their interaction with specific pathogen-associated molecules. However, while IRF3-activating pathways are increasingly well characterized, the cellular molecules involved in HCMV-mediated IRF3-dependent beta interferon transcription are virtually unknown. We undertook a systematic examination of new and established IRF3-terminal pathway components to identify those that are essential to HCMV-triggered IRF3 activation. We show here that IRF3 activation induced by HCMV infection involves the newly identified protein STING but, in contrast to infections with other herpesviruses, occurs independently of the adaptor molecule IPS-1. We also show that the protein DDX3 contributes to HCMV-triggered expression of beta interferon. Moreover, we identify Z-DNA binding protein 1 (ZBP1) as being essential for IRF3 activation and interferon beta expression triggered by HCMV, as well as being sufficient to enhance HCMV-stimulated beta interferon transcription and secretion. ZBP1 transcription was also found to be induced following exposure to HCMV in a JAK/STAT-dependent manner, thus perhaps also contributing to a positive feedback signal. Finally, we show that constitutive overexpression of ZBP1 inhibits HCMV replication. ZBP1 was recently identified as a cytosolic pattern recognition receptor of double-stranded DNA, and thus, we propose a model for HCMV-mediated IRF3 activation that involves HCMV-associated DNA as the principal innate immune-activating pathogen-associated molecular pattern. C1 [DeFilippis, Victor R.; Alvarado, David; Sali, Tina; Frueh, Klaus] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. [Rothenburg, Stefan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP DeFilippis, VR (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. EM defilipp@ohsu.edu RI Rothenburg, Stefan/A-8340-2008 FU American Heart Association [0730325N]; Medical Research Foundation of Oregon; NIH [R01AI070890] FX This work was supported by American Heart Association grant 0730325N (V.R. D.), a grant from the Medical Research Foundation of Oregon (V.R.D.), and NIH grant R01AI070890 (K.J.F.). NR 85 TC 71 Z9 77 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2010 VL 84 IS 1 BP 585 EP 598 DI 10.1128/JVI.01748-09 PG 14 WC Virology SC Virology GA 530BQ UT WOS:000272564300055 PM 19846511 ER PT J AU Cheng, C Gall, JGD Nason, M King, CR Koup, RA Roederer, M McElrath, MJ Morgan, CA Churchyard, G Baden, LR Duerr, AC Keefer, MC Graham, BS Nabel, GJ AF Cheng, Cheng Gall, Jason G. D. Nason, Martha King, C. Richter Koup, Richard A. Roederer, Mario McElrath, M. Juliana Morgan, Cecilia A. Churchyard, Gavin Baden, Lindsey R. Duerr, Ann C. Keefer, Michael C. Graham, Barney S. Nabel, Gary J. TI Differential Specificity and Immunogenicity of Adenovirus Type 5 Neutralizing Antibodies Elicited by Natural Infection or Immunization SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINE VECTORS; HIV-1 VACCINE; GENE-TRANSFER; IMMUNITY; HUMANS; STEP; SEROTYPE-5; RESPONSES; AFRICA; SAFETY AB A recent clinical trial of a T-cell-based AIDS vaccine delivered with recombinant adenovirus type 5 (rAd5) vectors showed no efficacy in lowering viral load and was associated with increased risk of human immunodeficiency virus type 1 (HIV-1) infection. Preexisting immunity to Ad5 in humans could therefore affect both immunogenicity and vaccine efficacy. We hypothesized that vaccine-induced immunity is differentially affected, depending on whether subjects were exposed to Ad5 by natural infection or by vaccination. Serum samples from vaccine trial subjects receiving a DNA/rAd5 AIDS vaccine with or without prior immunity to Ad5 were examined for the specificity of their Ad5 neutralizing antibodies and their effect on HIV-1 immune responses. Here, we report that rAd5 neutralizing antibodies were directed to different components of the virion, depending on whether they were elicited by natural infection or vaccination in HIV vaccine trial subjects. Neutralizing antibodies elicited by natural infection were directed largely to the Ad5 fiber, while exposure to rAd5 through vaccination elicited antibodies primarily to capsid proteins other than fiber. Notably, preexisting immunity to Ad5 fiber from natural infection significantly reduced the CD4 and CD8 cell responses to HIV Gag after DNA/rAd5 vaccination. The specificity of Ad5 neutralizing antibodies therefore differs depending on the route of exposure, and natural Ad5 infection compromises Ad5 vaccine-induced immunity to weak immunogens, such as HIV-1 Gag. These results have implications for future AIDS vaccine trials and the design of next-generation gene-based vaccine vectors. C1 [Cheng, Cheng; Nason, Martha; Koup, Richard A.; Roederer, Mario; Graham, Barney S.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Gall, Jason G. D.; King, C. Richter] GenVec Inc, Gaithersburg, MD 20878 USA. [McElrath, M. Juliana; Morgan, Cecilia A.; Duerr, Ann C.] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98109 USA. [Churchyard, Gavin] KOSH, ZA-2107 Marshalltown, South Africa. [Baden, Lindsey R.] Brigham & Womens Hosp, HIV Vaccine Trials Network, Boston, MA 02115 USA. [Keefer, Michael C.] Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU Intramural Research Program of the NIH; Vaccine Research Center, NIAID FX We declare that we have no material conflicts of interest, although intellectual property applications have been filed through the National Institutes of Health on the background DNA/rAd5 vaccine reported here. NR 22 TC 38 Z9 39 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2010 VL 84 IS 1 BP 630 EP 638 DI 10.1128/JVI.00866-09 PG 9 WC Virology SC Virology GA 530BQ UT WOS:000272564300059 PM 19846512 ER PT J AU Joiner, WM FitzGibbon, EJ Wurtz, RH AF Joiner, Wilsaan M. FitzGibbon, Edmond J. Wurtz, Robert H. TI Amplitudes and directions of individual saccades can be adjusted by corollary discharge SO JOURNAL OF VISION LA English DT Article DE corollary discharge; saccadic eye movement; movement vector ID FRONTAL EYE FIELD; BRAIN-STEM TELLS; SUPERIOR COLLICULUS; MOVEMENTS; THALAMUS; CORTEX; MONKEY; SEQUENCES; PATHWAY; SIGNALS AB There is strong evidence that the brain can use an internally generated copy of motor commands, a corollary discharge, to guide rapid sequential saccades. Much of this evidence comes from the double-step paradigm: after two briefly flashed visual targets have disappeared, the subject makes two sequential saccades to the targets. Recent studies on the monkey revealed that amplitude variations of the first saccade led to compensation by the second saccade, mediated by a corollary discharge. Here, we investigated whether such saccade-by-saccade compensation occurs in humans, and we made three new observations. First, we replicated previous findings from the monkey: following first saccade amplitude variations, the direction of the second saccade compensated for the error. Second, the change in direction of the second saccade followed variations in vertical as well as horizontal first saccades although the compensation following horizontal saccades was significantly more accurate. Third, by examining oblique saccades, we are able to show that first saccade variations are compensated by adjustment in saccade amplitude in addition to direction. Together, our results demonstrate that it is likely that a corollary discharge in humans can be used to adjust both saccade direction and amplitude following variations in individual saccades. C1 [Joiner, Wilsaan M.; FitzGibbon, Edmond J.; Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Joiner, WM (reprint author), NEI, Sensorimotor Res Lab, NIH, Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. EM joinerw@nei.nih.gov FU National Eye Institute Intramural Research Program FX This work was supported by the National Eye Institute Intramural Research Program. We are grateful for the continuing advice of our colleague Christian Quaia during these experiments, and for discussions with Neeraj Gandhi, Rebecca Berman, and Richard Krauzlis. NR 23 TC 16 Z9 16 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2010 VL 10 IS 2 AR 22 DI 10.1167/10.2.22 PG 12 WC Ophthalmology SC Ophthalmology GA 573ED UT WOS:000275890300022 ER PT J AU Quaia, C Joiner, WM FitzGibbon, EJ Optican, LM Smith, MA AF Quaia, Christian Joiner, Wilsaan M. FitzGibbon, Edmond J. Optican, Lance M. Smith, Maurice A. TI Eye movement sequence generation in humans: Motor or goal updating? SO JOURNAL OF VISION LA English DT Article DE eye movements; memory; plasticity ID CONTEXT-SPECIFIC ADAPTATION; TERM SACCADIC ADAPTATION; INTERNALLY TRIGGERED SACCADES; SCANNING VOLUNTARY SACCADES; HAND-POINTING MOVEMENTS; GAIN ADAPTATION; PARAMETRIC ADJUSTMENT; VISUAL LOCALIZATION; STEP STIMULI; PLASTICITY AB Saccadic eye movements are often grouped in pre-programmed sequences. The mechanism underlying the generation of each saccade in a sequence is currently poorly understood. Broadly speaking, two alternative schemes are possible: first, after each saccade the retinotopic location of the next target could be estimated, and an appropriate saccade could be generated. We call this the goal updating hypothesis. Alternatively, multiple motor plans could be pre-computed, and they could then be updated after each movement. We call this the motor updating hypothesis. We used McLaughlin's intra-saccadic step paradigm to artificially create a condition under which these two hypotheses make discriminable predictions. We found that in human subjects, when sequences of two saccades are planned, the motor updating hypothesis predicts the landing position of the second saccade in two-saccade sequences much better than the goal updating hypothesis. This finding suggests that the human saccadic system is capable of executing sequences of saccades to multiple targets by planning multiple motor commands, which are then updated by serial subtraction of ongoing motor output. C1 [Quaia, Christian; Joiner, Wilsaan M.; FitzGibbon, Edmond J.; Optican, Lance M.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. [Smith, Maurice A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Smith, Maurice A.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. RP Quaia, C (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA. EM quaiac@nei.nih.gov NR 107 TC 11 Z9 11 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2010 VL 10 IS 14 AR 28 DI 10.1167/10.14.28 PG 31 WC Ophthalmology SC Ophthalmology GA 763BV UT WOS:000290529100028 ER PT J AU Zou, SG Carey, JR Liedo, P Ingram, DK Yu, BB Ghaedian, R AF Zou, Sige Carey, James R. Liedo, Pablo Ingram, Donald K. Yu, Binbing Ghaedian, Reza TI Prolongevity Effects of an Oregano and Cranberry Extract are Diet Dependent in the Mexican Fruit Fly (Anastrepha ludens) SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Life span; Botanical extract; Aging intervention; Reproduction; Egg laying ID URINARY-TRACT-INFECTIONS; LIFE-SPAN; PHYTOCHEMICAL SYNERGIES; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; CANCER PREVENTION; IN-VIVO; RESTRICTION; RESVERATROL; MORTALITY AB Botanicals have numerous health benefits. Here, we used the Mexican fruit fly to screen 14 compounds and botanicals for their prolongevity effects and found an oregano and cranberry mixture (OC) improved survival. We then evaluated prolongevity effects of OC within the context of diet composition. Individual flies were fed 0%, 1%, or 2% OC in one of the three diets containing sugar and yeast extract (SY) at a ratio of 3:1, 9:1, or 24:1. We found that prolongevity effects of OC depended upon dose, gender, and diet composition. The greatest increase in longevity was observed in females fed the SY24:1 diet with 2% OC compared to the non-supplemented diet. OC did not reduce egg laying and, hence, did not compromise fecundity under any dietary condition tested here. This study reveals the prolongevity effects of OC and supports the emerging view that benefits of botanicals on aging depend on diet composition and gender. C1 [Zou, Sige] NIA, Funct Genom Unit, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Carey, James R.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Liedo, Pablo] El Colegio Frontera Sur, Tapachula, Chiapas, Mexico. [Ingram, Donald K.] Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. [Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. [Ghaedian, Reza] Decas Cranberry Prod Inc, Carver, MA USA. RP Zou, SG (reprint author), NIA, Funct Genom Unit, Lab Expt Gerontol, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM zous@grc.nia.nih.gov RI Trejo, Yesenia/D-9257-2012; Liedo, Pablo/E-9313-2010 OI Liedo, Pablo/0000-0002-0004-1721 FU National Institute on Aging, National Institutes of Health [P01-AG022500-01, P01-AG08761-10]; Ellison Medical Foundation; Cranberry Institute FX National Institute on Aging, National Institutes of Health, to J. R. C. (P01-AG022500-01; P01-AG08761-10), Ellison Medical Foundation to J. R. C. and S. Z., and Cranberry Institute to S. Z. and Intramural Research Program at the National Institute on Aging, National Institutes of Health, to S. Z. NR 63 TC 15 Z9 15 U1 1 U2 5 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2010 VL 65 IS 1 BP 41 EP 50 DI 10.1093/gerona/glp176 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 537LV UT WOS:000273115300006 PM 19906819 ER PT J AU Ferrucci, L Studenski, SA Alley, DE Barbagallo, M Harris, TB AF Ferrucci, Luigi Studenski, Stephanie A. Alley, Dawn E. Barbagallo, Mario Harris, Tamara B. TI Obesity in Aging and Art SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 [Ferrucci, Luigi] Harbor Hosp, Longitudinal Studies Sect, Clin Res Branch, NIA,ASTRA Unit, Baltimore, MD 21225 USA. [Studenski, Stephanie A.] Univ Pittsburgh, Div Geriatr & Gerontol, Pittsburgh, PA USA. [Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Barbagallo, Mario] Univ Palermo, Dept Geriatr, Palermo, Italy. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), Harbor Hosp, Longitudinal Studies Sect, Clin Res Branch, NIA,ASTRA Unit, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov OI BARBAGALLO, MARIO/0000-0002-1349-6530 FU Intramural NIH HHS NR 11 TC 3 Z9 3 U1 0 U2 2 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2010 VL 65 IS 1 BP 53 EP 56 DI 10.1093/gerona/glp166 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 537LV UT WOS:000273115300007 PM 19920069 ER PT J AU Lee, JS Visser, M Tylavsky, FA Kritchevsky, SB Schwartz, AV Sahyoun, N Harris, TB Newman, AB AF Lee, Jung Sun Visser, Marjolein Tylavsky, Frances A. Kritchevsky, Stephen B. Schwartz, Ann V. Sahyoun, Nadine Harris, Tamara B. Newman, Anne B. CA Hlth ABC Study TI Weight Loss and Regain and Effects on Body Composition: The Health, Aging, and Body Composition Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Weight cycle; Body composition; Older adults ID FAT-FREE MASS; DWELLING OLDER-ADULTS; X-RAY ABSORPTIOMETRY; CRITERION METHODS; UNITED-STATES; WOMEN; AGE; HISTORY; TISSUE; COHORT AB Older adults are less able to conserve lean mass relative to fat mass with weight change. A cycle of weight loss and regain in an older individual could accelerate sarcopenia. We examined whether older adults experiencing weight loss and regain would show a greater loss of lean mass during a weight-loss period than gain in lean mass during the weight-regain period, thus have overall a greater net loss of lean mass compared with those who maintained weight in the Health, Aging, and Body Composition Study. We compared the body composition change in 147 older weight changers (54% women, 38% black) with the gender- and race-matched weight-stable individuals over the weight-cycling period. A weight cycle was defined as weight loss of 3% or more with regain of within +/- 3% of baseline weight for a period of 2 years. Both men and women showed significantly lower total body mass after the weight loss and regain. Proportionally, more lean mass was lost during the weight-loss period than was gained during the weight-regain period, especially in men. After weight regain, men showed only a slightly lower lean mass than the stable group, and this was not statistically significant, although the failure to fully regain total weight explained most of the deficit in lean mass after the weight cycle. These data suggest that weight loss even with regain may contribute to a net loss of lean mass in older men but warrant further studies. C1 [Lee, Jung Sun] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands. [Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Nutr & Hlth, Amsterdam, Netherlands. [Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Winston Salem, NC 27103 USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Sahyoun, Nadine] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Lee, JS (reprint author), Univ Georgia, Dept Foods & Nutr, 129 Barrow Hall, Athens, GA 30602 USA. EM leejs@fcs.uga.edu RI Sahyoun, Nadine/G-2608-2011; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institutes of Health, National Institute on Aging FX Supported by National Institute on Aging contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging NR 31 TC 37 Z9 38 U1 4 U2 16 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2010 VL 65 IS 1 BP 78 EP 83 DI 10.1093/gerona/glp042 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 537LV UT WOS:000273115300011 PM 19366882 ER PT J AU Stenholm, S Koster, A Alley, DE Houston, DK Kanaya, A Lee, JS Newman, AB Satterfield, S Simonsick, EM Visser, M Harris, TB Ferrucci, L AF Stenholm, Sari Koster, Annemarie Alley, Dawn E. Houston, Denise K. Kanaya, Alka Lee, Jung Sun Newman, Anne B. Satterfield, Suzanne Simonsick, Eleanor M. Visser, Marjolein Harris, Tamara B. Ferrucci, Luigi CA Hlth Aging Body Composition Study TI Joint Association of Obesity and Metabolic Syndrome With Incident Mobility Limitation in Older Men and Women-Results From the Health, Aging, and Body Composition Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Obesity; Metabolic syndrome; Mobility limitation; Inflammation; Older people ID COMMUNITY-BASED SAMPLE; MASS INDEX; INSULIN-RESISTANCE; PHYSICAL FUNCTION; MUSCLE STRENGTH; KNEE OSTEOARTHRITIS; WALKING LIMITATION; FAT DISTRIBUTION; US POPULATION; ADULTS AB Although both obesity and the metabolic syndrome (MetS) are known risk factors for decline in physical function, the joint association of obesity and metabolic alterations with risk of incident mobility limitation is unknown. Data are from 2,984 women and men aged 70-79 years participating in the Health, Aging, and Body Composition Study without mobility limitation at baseline. Obesity was defined as body mass index greater than or equal to 30 kg/m(2) and the MetS as meeting greater than or equal to 3 of the ATP III criteria. Mobility limitation was defined as any difficulty walking one-quarter mile or climbing 10 steps during two consecutive semiannual assessments for more than 6.5 years. Incidence of mobility limitation was 55% in women and 44% in men. In women, adjusted risk of developing mobility limitation was progressively greater in nonobese participants with the MetS (hazard ratio [HR] = 1.49, 95% confidence interval [CI] = 1.24-1.80), obese participants without the MetS (HR = 1.95, 95% CI = 1.51-2.53), and obese participants with the MetS (HR = 2.16, 95% CI = 1.78-2.63) relative to the nonobese without the MetS. In men, the corresponding adjusted HRs (95% CI) were 1.07 (0.87-1.32), 1.64 (1.19-2.25), and 1.41 (1.12-1.78). Elevated inflammatory markers partly explained the association between obesity, the MetS, and mobility limitation, particularly in nonobese and obese participants with the MetS. Obesity itself, independent of its metabolic consequences, is a risk factor for mobility limitation among obese older adults. In addition, having the MetS increases the risk of functional decline in older nonobese women but not in men. C1 [Stenholm, Sari] Harbor Hosp, Longitudinal Studies Sect, Clin Res Branch, NIA, Baltimore, MD 21225 USA. [Stenholm, Sari] Div Welf & Hlth Policies, Living Condit Hlth & Wellbeing Unit, Helsinki, Finland. [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Houston, Denise K.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Kanaya, Alka] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Lee, Jung Sun] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Dept Hlth Sci, Amsterdam, Netherlands. [Visser, Marjolein] Vrije Univ Amsterdam, EMGO Inst, Amsterdam, Netherlands. RP Stenholm, S (reprint author), Harbor Hosp, Longitudinal Studies Sect, Clin Res Branch, NIA, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM stenholmsm@mail.nih.gov RI Koster, Annemarie/E-7438-2010; Stenholm, Sari/G-6940-2011; Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institutes of Health, NIA; Finnish Academy [125494 SS] FX This work was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the National Institutes of Health, NIA. This work was also supported by grant from the Finnish Academy (No. 125494 SS). NR 40 TC 20 Z9 21 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2010 VL 65 IS 1 BP 84 EP 92 DI 10.1093/gerona/glp150 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 537LV UT WOS:000273115300012 PM 19822624 ER PT J AU Stenholm, S Simonsick, EM Ferrucci, L AF Stenholm, Sari Simonsick, Eleanor M. Ferrucci, Luigi TI Secular Trends in Body Weight in Older Men Born Between 1877 and 1941: The Baltimore Longitudinal Study of Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Obesity; BSLA; Body weight; Old age ID ALL-CAUSE MORTALITY; MASS INDEX; WAIST CIRCUMFERENCE; PHYSICAL-ACTIVITY; OBESITY EPIDEMIC; UNITED-STATES; ADULTS; OVERWEIGHT; HEALTH; AGE AB The prevalence of overweight and obesity has increased in all age groups, including older adults. However, it is not known whether higher body weight is maintained in the very old and in the years prior to death. The present study examines whether there are secular trends in body weight in old age among three birth cohorts. The study population includes 1,364 Caucasian men born between 1877 and 1941 from the Baltimore Longitudinal Study of Aging who were followed until death. Four hundred and seventy-seven men had body weight measured during the last 5 years prior to death. Body weight was measured biannually with the last visit occurring between 1959 and 2008. Differences in body weight at the last visit and body weight trajectories across birth cohorts were examined with linear regression and linear mixed-effect regression models. Men born between 1920 and 1941 had significantly higher body weight over the entire follow-up time compared with men born between 1900 and 1919 (p < .001) and 1877 and 1899 (p = .001), and the difference was also significant between the two earlier birth cohorts (p < .001). A significant increasing trend in body weight across birth cohorts was also observed in the few years prior to death. In generally healthy men, there is a significant secular increase in body weight over the adult life span and in the few years prior to death. This study confirms that the obesity epidemic also extends into late life in the current elderly population. C1 [Stenholm, Sari] Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD 21225 USA. [Stenholm, Sari] Natl Inst Hlth & Welf, Div Welf & Hlth Policies, Helsinki, Finland. RP Stenholm, S (reprint author), Harbor Hosp, NIA, Clin Res Branch, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM stenholmsm@mail.nih.gov RI Stenholm, Sari/G-6940-2011 FU National Institutes of Health, National Institute on Aging; Finnish Academy [125494] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. This work was also supported by grant from the Finnish Academy (no. 125494 to S. S.). NR 37 TC 9 Z9 9 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2010 VL 65 IS 1 BP 105 EP 110 DI 10.1093/gerona/glp178 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 537LV UT WOS:000273115300015 PM 19933750 ER PT J AU Yang, MH Sun, S Kostov, Y Rasooly, A AF Yang, Minghui Sun, Steven Kostov, Yordan Rasooly, Avraham TI Lab-on-a-chip for carbon nanotubes based immunoassay detection of Staphylococcal Enterotoxin B (SEB) SO LAB ON A CHIP LA English DT Article ID FIELD-EFFECT TRANSISTORS; ENHANCED CHEMILUMINESCENCE IMMUNOASSAY; ASSAY KIT TECRA; ELECTROCHEMICAL IMMUNOSENSOR; FOOD; DEVICES; TOXIN; ADSORPTION; NETWORKS; RICIN AB We describe a new eight channel Lab-On-a-Chip (LOC) for a Carbon Nanotube (CNT) based immunoassay with optical detection of Staphylococcal Enterotoxin B (SEB) for food safety applications. In this work, we combined four biosensing elements: (1) CNT technology for primary antibody immobilization, (2) Enhanced Chemiluminescence (ECL) for light signal generation, (3) a cooled charge-coupled device (CCD) for detection and (4) polymer lamination technology for developing a point of care immunological assay for SEB detection. Our concept for developing versatile LOCs, which can be used for many different applications, is to use a modular design with interchangeable recognition elements (e. g. various antibodies) to determine the specificity. Polymer lamination technology was used for the fabrication of a six layer, syringe operated LOC capable of analyzing eight samples simultaneously. An anti-SEB antibody-nanotube mixture was immobilized onto a polycarbonate strip, to serve as an interchangeable ligand surface that was then bonded onto the LOC. SEB samples are loaded into the device and detected by an ELISA assay using Horse Radish Peroxidase (HRP) conjugated anti-SEB IgG as a secondary antibody and ECL, with detection by a previously described portable cooled CCD detector. Eight samples of SEB in buffer or soy milk were assayed simultaneously with a limit of detection of 0.1 ng mL(-1). CNT immobilization of the antibody increased the sensitivity of detection six fold. Use of a simple interchangeable immunological surface allows this LOC to be adapted to any immunoassay by simply replacing the ligand surface. A syringe was used to move fluids for this assay so no power is needed to operate the device. Our versatile portable point-of-care CCD detector combined with the LOC immunoassay method described here can be used to reduce the exposure of users to toxins and other biohazards when working outside the lab, as well as to simplify and increase sensitivity for many other types of immunological diagnostics and detection assays. C1 [Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov RI Zhou, Feng/E-9510-2011; OI zaraat, javad/0000-0001-5341-7481 NR 50 TC 42 Z9 43 U1 4 U2 30 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2010 VL 10 IS 8 BP 1011 EP 1017 DI 10.1039/b923996k PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 577JL UT WOS:000276218900007 PM 20358108 ER PT J AU Sun, S Yang, MH Kostov, Y Rasooly, A AF Sun, Steven Yang, Minghui Kostov, Yordan Rasooly, Avraham TI ELISA-LOC: lab-on-a-chip for enzyme-linked immunodetection SO LAB ON A CHIP LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-B; ENHANCED CHEMILUMINESCENCE IMMUNOASSAY; CARBON NANOTUBES; ARRAY BIOSENSOR; MICROFLUIDIC DEVICE; FOODS; ANTIBODIES; ASSAY; FLOW; IMMUNOSENSOR AB A miniature 96 sample ELISA-lab-on-a-chip (ELISA-LOC) was designed, fabricated, and tested for immunological detection of Staphylococcal Enterotoxin B (SEB). The chip integrates a simple microfluidics system into a miniature ninety-six sample plate, allowing the user to carry out an immunological assay without a laboratory. Assay reagents are delivered into the assay plate without the need for separate devices commonly used in immunoassays. The ELISA-LOC was constructed using Laminated Object Manufacturing (LOM) technology to assemble six layers with an acrylic (poly(methyl methacrylate) (PMMA)) core and five polycarbonate layers micromachined by a CO(2) laser. The ELISA-LOC has three main functional elements: reagent loading fluidics, assay and detection wells, and reagent removal fluidics, a simple "surface tension'' valve used to control the flow. To enhance assay sensitivity and to perform the assay without a lab, ELISA-LOC detection combines several biosensing elements: (1) carbon nanotube (CNT) technology to enhance primary antibody immobilization, (2) sensitive ECL (electrochemiluminescence) detection, and (3) a charge-coupled device (CCD) detector for measuring the light signal generated by ECL. Using a sandwich ELISA assay, the system detected SEB at concentrations as low as 0.1 ng n ml(-1), which is similar to the reported sensitivity of conventional ELISA. The fluidics system can be operated by a syringe and does not require power for operation. This simple point-of-care (POC) system is useful for carrying out various immunological assays and other complex medical assays without a laboratory. C1 [Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Sun, Steven; Yang, Minghui; Kostov, Yordan] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov OI zaraat, javad/0000-0001-5341-7481 NR 45 TC 56 Z9 56 U1 4 U2 85 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2010 VL 10 IS 16 BP 2093 EP 2100 DI 10.1039/c003994b PG 8 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 632BK UT WOS:000280394800011 PM 20544092 ER PT J AU Yang, MH Sun, S Bruck, HA Kostov, Y Rasooly, A AF Yang, Minghui Sun, Steven Bruck, Hugh Alan Kostov, Yordan Rasooly, Avraham TI Lab-on-a-chip for label free biological semiconductor analysis of Staphylococcal Enterotoxin B SO LAB ON A CHIP LA English DT Article ID ATOPIC-DERMATITIS; CARBON NANOTUBES; ELECTRICAL PERCOLATION; RHEUMATOID-ARTHRITIS; REAL-TIME; FOOD; SEB; SUPERANTIGENS; MICROFLUIDICS; PREVALENCE AB We describe a new lab-on-a-chip (LOC) which utilizes a biological semiconductor (BSC) transducer for label free analysis of Staphylococcal Enterotoxin B (SEB) (or other biological interactions) directly and electronically. BSCs are new transducers based on electrical percolation through a multi-layer carbon nanotube-antibody network. In BSCs the passage of current through the conductive network is dependent upon the continuity of the network. Molecular interactions within the network, such as binding of antigens to the antibodies, disrupt the network continuity causing increased resistance of the network. For the fabrication of a BSC based detector, we combined several elements: (1) BSC transducers for direct detection, (2) LOC for flow through continuous measurements, (3) a digital multimeter with computer connection for data logging, (4) pumps and valves for fluid delivery, and (5) a computer for fluid delivery control and data analysis. Polymer lamination technology was used for the fabrication of a four layer LOC for BSC detection, the BSC on the chip is fabricated by immobilizing pre-functionalized single-walled carbon nanotubes (SWNTs)-antibody complex directly on the PMMA surface of the LOC. SEB samples were loaded into the device using a peristaltic pump and the change in resistance resulting from antibody-antigen interactions was continuously monitored and recorded. Binding of SEB rapidly increases the BSC electrical resistance. SEB in buffer was assayed with limit of detection (LOD) of 5 ng mL(-1) at a signal to baseline (S/B) ratio of 2. A secondary antibody was used to verify the presence of the SEB captured on the surface of the BSC and for signal amplification. The new LOC system permits rapid detection and semi-automated operation of BSCs. Such an approach may enable the development of multiple biological elements "Biological Central Processing Units (CPUs)'' for parallel processing and sorting out automatically information on multiple analytes simultaneously. Such an approach has potential use for point-of-care medical and environmental testing. C1 [Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Bruck, Hugh Alan] UMCP, College Pk, MD 20742 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. [Rasooly, Avraham] NCI, NIH, Rockville, MD 20852 USA. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov OI zaraat, javad/0000-0001-5341-7481 NR 31 TC 10 Z9 10 U1 2 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2010 VL 10 IS 19 BP 2534 EP 2540 DI 10.1039/c005141a PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 647JN UT WOS:000281614900007 PM 20668726 ER PT J AU Simonyan, K Ludlow, CL Vortmeyer, AO AF Simonyan, Kristina Ludlow, Christy L. Vortmeyer, Alexander O. TI Brainstem Pathology in Spasmodic Dysphonia SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 109th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation CY SEP 25-28, 2005 CL Los Angeles, CA SP Amer Acad Otolaryngol Head & Neck Surg Fdn DE Laryngeal dystonia; neuropathology; immunohistochemistry ID MEIGE SYNDROME; DYSTONIA; NEUROPATHOLOGY; DISEASE AB Spasmodic dysphonia (SD) is a primary focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal. muscles during speech production. We examined two rare cases of postmortem brainstem tissue from SD patients compared to Tour controls. In the SD patients, small clusters of inflammation were found in the reticular formation surrounding solitary tract, spinal trigeminal, and ambigual nuclei, inferior olive, and pyramids. Mild neuronal, degeneration and depigmentation were observed in the substantia nigra and locus coeruleus. No mal, protein accumulations and no demyelination or axonal degeneration were found. These neuropathological findings may provide insights into the pathophysiology of SD. C1 [Simonyan, Kristina; Ludlow, Christy L.] Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20814 USA. [Vortmeyer, Alexander O.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20814 USA. RP Simonyan, K (reprint author), Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, Med Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D38, Bethesda, MD 20814 USA. EM simonyak@ninds.nih.gov OI Simonyan, Kristina/0000-0001-7444-0437; Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS [Z01 NS002980-08, Z99 NS999999] NR 12 TC 11 Z9 13 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2010 VL 120 IS 1 BP 121 EP 124 DI 10.1002/lary.20677 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 539HZ UT WOS:000273245900022 PM 19795469 ER PT S AU Steers, E AF Steers, Edward, Jr. BE Holzer, H Symonds, CL Williams, FJ TI "Let the Stain of Innocent Blood Be Removed from the Land" The Military Trial of the Lincoln Conspirators SO LINCOLN ASSASSINATION: CRIME AND PUNISHMENT, MYTH AND MEMORY SE Norths Civil War LA English DT Article; Book Chapter C1 [Steers, Edward, Jr.] Natl Inst Hlth, Bethesda, MD USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU FORDHAM UNIV PRESS PI BRONX PA UNIV BOX L, BRONX, NY 10458 USA SN 1089-8719 BN 978-0-8232-3226-0 J9 N CIVIL WAR PY 2010 BP 175 EP 194 D2 10.5422/fso/9780823232260.001.0001 PG 20 WC History SC History GA BYB70 UT WOS:000297842700008 ER PT S AU Hristovski, D Kastrin, A Peterlin, B Rindflesch, TC AF Hristovski, Dimitar Kastrin, Andrej Peterlin, Borut Rindflesch, Thomas C. BE Blaschke, C Shatkay, H TI Combining Semantic Relations and DNA Microarray Data for Novel Hypotheses Generation SO LINKING LITERATURE, INFORMATION, AND KNOWLEDGE FOR BIOLOGY SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT Workshop of the BioLINK Special Interest Group on Linking Literature, Information and Knowledge for Biology CY JUN 28-29, 2009 CL Stockholm, SWEDEN SP Int Soc Comp Biol, Spanish Natl Canc Res Ctr, BioCreat II.5 challenge DE microarray analysis; literature-based discovery; semantic predications; natural language processing ID BIOMEDICAL TEXT; PARKINSONS-DISEASE; DISCOVERY; KNOWLEDGE; GENE AB Although microarray experiments have great potential to support progress in biomedical research, results are not easy to interpret. Information about the functions and relations of relevant genes needs to be extracted from the vast biomedical literature. A potential solution is to use computerized text analysis methods. Our proposal enhances these methods with semantic relations. We describe an application that integrates such relations with microarray results and discuss its benefits in supporting enhanced access to the relevant literature for interpretation of results and novel hypotheses generation. The application is available at http://sembt.mf.uni-lj.si C1 [Hristovski, Dimitar] Univ Ljubljana, Fac Med, Inst Biomed Informat, Ljubljana, Slovenia. [Kastrin, Andrej; Peterlin, Borut] Univ Med Ctr, Inst Med Genet, Ljubljana, Slovenia. [Rindflesch, Thomas C.] NIH, Natl Lib Med, Bethesda, MD USA. RP Hristovski, D (reprint author), Univ Ljubljana, Fac Med, Inst Biomed Informat, Ljubljana, Slovenia. EM dimitar.hristovski@mf.uni-lj.si; andrej.kastrin@guest.arnes.si; borut.peterlin@guest.arnes.si; tcr@nlm.nih.gov NR 22 TC 7 Z9 8 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-13130-1 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2010 VL 6004 BP 53 EP + DI 10.1007/978-3-642-13131-8_7 PG 3 WC Biochemical Research Methods; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BST13 UT WOS:000285733500007 ER PT S AU Sohn, HW Tolar, P Brzostowski, J Pierce, SK AF Sohn, Hae Won Tolar, Pavel Brzostowski, Joseph Pierce, Susan K. BE Papkovsky, DB TI A Method for Analyzing Protein-Protein Interactions in the Plasma Membrane of Live B Cells by Fluorescence Resonance Energy Transfer Imaging as Acquired by Total Internal Reflection Fluorescence Microscopy SO LIVE CELL IMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE B lymphocyte; fluorescence resonance energy transfer (FRET); total internal reflection fluorescence (TIRF) imaging; B cell receptor (BCR) signaling; planar lipid bilayer; immune synapse ID LIVING CELLS; INITIATION; ACTIVATION AB For more than a decade, fluorescence resonance energy transfer (FRET) imaging methods have been developed to Study dynamic interactions between molecules at the nanometer scale in live cells. Here, we describe a protocol to measure FRET by the acceptor-sensitized emission method as detected by total internal reflection fluorescence (TIRF) imaging to Study the interaction of appropriately labeled plasma membrane-associated Molecules that regulate the earliest stages of antigen-mediated signaling in live B lymphocytes. This protocol can be adapted and applied to many cell types where there is an interest in understanding signal transduction mechanisms in live cells. C1 [Sohn, Hae Won; Tolar, Pavel; Brzostowski, Joseph; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sohn, HW (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. FU Intramural NIH HHS [ZIA AI000975-06, ZIA AI001126-02, Z01 AI000899-08, Z01 AI000898-08] NR 15 TC 9 Z9 10 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-403-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 591 BP 159 EP 183 DI 10.1007/978-1-60761-404-3_10 D2 10.1007/978-1-60761-404-3 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNC63 UT WOS:000274162900010 PM 19957130 ER PT J AU Moss, J AF Moss, Joel TI Introduction SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Editorial Material RP Moss, J (reprint author), NHLBI, Translat Med Branch, NIH, 10 Ctr Dr,Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PY 2010 VL 8 IS 1 BP 3 EP 3 DI 10.1089/lrb.2010.8102 PG 1 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA 598WO UT WOS:000277870500002 PM 20235881 ER PT J AU Peavy, H Gail, D Kiley, J Shurin, S AF Peavy, Hannah Gail, Dorothy Kiley, James Shurin, Susan TI A National Heart, Lung, and Blood Institute History and Perspective on Lymphangioleiomyomatosis SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; SPORADIC LYMPHANGIOLEIOMYOMATOSIS; GENE; TSC2; SIROLIMUS; CELLS; LYMPHANGIOMYOMATOSIS; TRANSPLANTATION; IDENTIFICATION RP Kiley, J (reprint author), NHLBI, Div Lung Dis, 6701 Rockledge Dr,Room 10018, Bethesda, MD 20892 USA. EM kileyj@nhlbi.nih.gov NR 23 TC 2 Z9 2 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PY 2010 VL 8 IS 1 BP 5 EP 8 DI 10.1089/lrb.2009.0023 PG 4 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA 598WO UT WOS:000277870500003 PM 20235882 ER PT J AU Taveira-DaSilva, AM Pacheco-Rodriguez, G Moss, J AF Taveira-DaSilva, Angelo M. Pacheco-Rodriguez, Gustavo Moss, Joel TI The Natural History of Lymphangioleiomyomatosis: Markers of Severity, Rate of Progression and Prognosis SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; IDIOPATHIC PULMONARY-FIBROSIS; GROWTH FACTOR-D; MATRIX METALLOPROTEINASES; LYMPHATIC INVOLVEMENT; LUNG TRANSPLANTATION; LONGITUDINAL CHANGES; TISSUE INHIBITORS; DIURNAL-VARIATION; FUNCTION TESTS AB Lymphangioleiomyomatosis (LAM) is a multisystem disease of women, characterized by proliferation of abnormal smooth muscle-like cells (LAM cells) that can metastasize, leading to the formation of lung cysts, fluid-filled cystic structures in the axial lymphatics (e.g., lymphangioleiomyomas), and angiomyolipomas, benign tumors usually involving the kidneys, comprising LAM cells and adipocytes, intermixed with incompletely developed vascular structures. LAM occurs sporadically or in association with tuberous sclerosis complex, an autosomal dominant syndrome characterized by hamartoma-like tumor growths. LAM may present with progressive dyspnea, recurrent pneumothorax, chylothorax, or abdominal hemorrhage. Computed tomography scans show thin-walled cysts scattered throughout the lungs, abdominal angiomyolipomas, and lymphangioleiomyomas. Pulmonary function tests show reduced flow rates (FEV1) and diffusion capacity (DLCO). Exercise testing may reveal gas exchange abnormalities, ventilatory limitation, and hypoxemia, which can occur with near-normal lung function. Methods used to grade the severity of disease are the LAM histology score, semiquantitative and quantitative computer tomography, pulmonary function testing, and cardiopulmonary exercise testing. Currently, progression of disease is best assessed by serial measurements of FEV1, DLCO, and exercise performance. New quantitative radiographic techniques that may offer advantages over physiologic testing are now available. Several potential biomarkers, such as LAM cells in peripheral blood, urine, and chyle and chemokines, vascular endothelial growth factors, and matrix metalloproteinases, may be useful as diagnostic tools or markers of organ involvement, disease severity, and progression. RP Taveira-DaSilva, AM (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM dasilvaa@nhlbi.nih.gov FU NIH, NHLBI FX The authors thank Dr. Martha Vaughan (NHLBI, NIH, Bethesda, MD) for critical review of the manuscript and helpful discussions. We thank the LAM Foundation and the Tuberous Sclerosis Alliance for referring patients for participation in these studies, which were also supported in part by the Intramural Research Program, NIH, NHLBI. NR 98 TC 38 Z9 39 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 EI 1557-8585 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PY 2010 VL 8 IS 1 BP 9 EP 19 DI 10.1089/lrb.2009.0024 PG 11 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA 598WO UT WOS:000277870500004 PM 20235883 ER PT J AU Darling, TN Pacheco-Rodriguez, G Gorio, A Lesma, E Walker, C Moss, J AF Darling, Thomas N. Pacheco-Rodriguez, Gustavo Gorio, Alfredo Lesma, Elena Walker, Cheryl Moss, Joel TI Lymphangioleiomyomatosis and TSC2(-/-) Cells SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; SINGLE-LUNG TRANSPLANTATION; TUMOR-SUPPRESSOR GENE; EKER RAT MODEL; PROGESTERONE-RECEPTOR IMMUNOREACTIVITY; REPRODUCTIVE-TRACT LEIOMYOMATA; DOMINANTLY INHERITED CANCER; ANGIOFIBROMA STROMA CELLS; KINASE INHIBITOR P27; SMOOTH-MUSCLE-CELLS AB The cells comprising pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipomas (AMLs) are heterogeneous, with variable mixtures of cells exhibiting differentiation towards smooth muscle, fat, and vessels. Cells grown from LAM and AMLs have likewise tended to be heterogeneous. The discovery that LAM and AMLs contain cells with mutations in the TSC1 or TSC2 genes is allowing investigators to discriminate between "two-hit" cells and neighboring cells, providing insights into disease pathogenesis. In rare cases, it has been possible to derive cells from human tumors, including AMLs and TSC skin tumors that are highly enriched for TSC2(-/-) cells. Cells derived from an Eker rat uterine leiomyoma (ELT3 cells) are Tsc2-null and these have been used in a rodent cell models for LAM. Further improvements in the ability to reliably grow well-characterized TSC2(-/-) cells from human tumors are critical to developing in vitro and in vivo model systems for studies of LAM pathogenesis and treatment. C1 [Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. [Pacheco-Rodriguez, Gustavo; Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Gorio, Alfredo; Lesma, Elena] Univ Milan, Pharmacol Lab, Dept Med Surg & Dent, Fac Med, Milan, Italy. [Gorio, Alfredo] IRCCS Humanitas, Clin Pharmacol, Milan, Italy. [Walker, Cheryl] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM tdarling@usuhs.mil OI Darling, Thomas/0000-0002-5161-1974 FU National Institutes of Health, National Heart, Lung, and Blood Institute; Ministero Superiore della Sanita (IRCCS) [2007-09]; Italian TSC Association; Italian Lymphangioleiomyomatosis Association; Congressionally Directed Medical Research Program [TS080064] FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute, and TS080064 from the Congressionally Directed Medical Research Program (TND). The work of A. Gorio and E. Lesma was supported by the Ministero Superiore della Sanita (IRCCS Grant 2007-09 on rare diseases program), the Italian TSC Association, and the Italian Lymphangioleiomyomatosis Association. We thank the Tuberous Sclerosis Alliance and The LAM Foundation for patient referral. We thank Dr. Martha Vaughan for useful discussions and critical review of the manuscript. NR 111 TC 13 Z9 14 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PY 2010 VL 8 IS 1 BP 59 EP 69 DI 10.1089/lrb.2009.0031 PG 11 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA 598WO UT WOS:000277870500009 PM 20235888 ER PT J AU Nurok, M Eslick, I Carvalho, CRR Costabel, U D'Armiento, J Glanville, AR Harari, S Henske, EP Inoue, Y Johnson, SR Lacronique, J Lazor, R Moss, J Ruoss, SJ Ryu, JH Seyama, K Watz, H Xu, KF Hohmann, EL Moss, F AF Nurok, Michael Eslick, Ian Carvalho, Carlos R. R. Costabel, Ulrich D'Armiento, Jeanine Glanville, Allan R. Harari, Sergio Henske, Elizabeth P. Inoue, Yoshikazu Johnson, Simon R. Lacronique, Jacques Lazor, Romain Moss, Joel Ruoss, Stephen J. Ryu, Jay H. Seyama, Kuniaki Watz, Henrik Xu, Kai-Feng Hohmann, Elizabeth L. Moss, Frank TI The International LAM Registry: A Component of an Innovative Web-Based Clinician, Researcher, and Patient-Driven Rare Disease Research Platform SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; LUNG TRANSPLANTATION; WOMEN AB Background: A relative friability to capture a sufficiently large patient population in any one geographic location has traditionally limited research into rare diseases. Methods and Results: Clinicians interested in the rare disease lymphangioleiomyomatosis (LAM) have worked with the LAM Treatment Alliance, the MIT Media Lab, and Clozure Associates to cooperate in the design of a state-of-the-art data coordination platform that can be used for clinical trials and other research focused on the global LAM patient population. This platform is a component of a set of web-based resources, including a patient self-report data portal, aimed at accelerating research in rare diseases in a rigorous fashion. Conclusions: Collaboration between clinicians, researchers, advocacy groups, and patients can create essential community resource infrastructure to accelerate rare disease research. The International LAM Registry is an example of such an effort. C1 [Nurok, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Surg Crit Care, Boston, MA 02115 USA. [Nurok, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiac, Boston, MA 02115 USA. [Nurok, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Thorac Anesthesia, Boston, MA 02115 USA. [Eslick, Ian; Moss, Frank] MIT, Media Lab, Cambridge, MA 02139 USA. [Carvalho, Carlos R. R.] Univ Sao Paulo, Heart Inst InCor, Div Pulm, Sao Paulo, Brazil. [Costabel, Ulrich] Ruhrlandklin Univ Klinikum, Dept Pneumol Allergy, Essen, Germany. [D'Armiento, Jeanine] Columbia Univ Coll Phys & Surg, Dept Med, Div Pulm & Crit Care, New York, NY 10032 USA. [Glanville, Allan R.] St Vincents Hosp, Div Thorac Med, Lung Transplantat Grp, Darlinghurst, NSW 2010, Australia. [Harari, Sergio] Osped San Giuseppe, Unita Pneumol & Terapia Semiintens Resp, Milan, Italy. [Henske, Elizabeth P.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Ctr LAM Res & Clin Care, Boston, MA 02115 USA. [Henske, Elizabeth P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Inoue, Yoshikazu] Natl Hosp Org Kinki Chuo, Chest Med Ctr, Clin Res Ctr, Dept Diffuse Lung Dis & Resp Failure, Osaka, Japan. [Johnson, Simon R.] Univ Nottingham, Div Therapeut & Mol Med, Nottingham NG7 2RD, England. [Johnson, Simon R.] Univ Nottingham, Nottingham Resp Biomed Res Unit, Nottingham NG7 2RD, England. [Lacronique, Jacques] Hop Cochin, Serv Pneumol, F-75674 Paris, France. [Lazor, Romain] CHU Vaudois, Clin Interstitial & Rare Lung Dis, Dept Resp Med, CH-1011 Lausanne, Switzerland. [Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Ruoss, Stephen J.] Stanford Univ, Med Ctr, Div Pulm & Crit Care Med, Stanford, CA 94305 USA. [Ryu, Jay H.] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA. [Seyama, Kuniaki] Juntendo Univ, Sch Med, Dept Resp Med, Tokyo 113, Japan. [Watz, Henrik] Krankenhaus Grosshansdorf, Zentrum Pneumol & Thoraxchirurg, Pneumol Forsch Inst GmbH, D-2070 Grosshansdorf, Germany. [Hohmann, Elizabeth L.] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Resp Med, Beijing 100037, Peoples R China. [Moss, Frank] Partners Healthcare, Partners Human Res Comm, Boston, MA USA. RP Nurok, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Surg Crit Care, 75 Francis St, Boston, MA 02115 USA. EM mnurok@partners.org RI Carvalho, Carlos/H-2161-2011; OI Harari, Sergio/0000-0001-8629-7391; Johnson, Simon/0000-0002-9837-2763 FU LAM Treatment Alliance [501(c)(3)] FX Source of Support: The LAM Treatment Alliance, 501(c)(3) NR 16 TC 7 Z9 7 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PY 2010 VL 8 IS 1 BP 81 EP 87 DI 10.1089/lrb.2009.0028 PG 7 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA 598WO UT WOS:000277870500011 PM 20235890 ER PT J AU Lu, HB Scholl, CA Zuo, YT Demny, S Rea, W Stein, EA Yang, YH AF Lu, Hanbing Scholl, Clara A. Zuo, Yantao Demny, Steven Rea, William Stein, Elliot A. Yang, Yihong TI Registering and analyzing rat fMRI data in the stereotaxic framework by exploiting intrinsic anatomical features SO MAGNETIC RESONANCE IMAGING LA English DT Article DE fMRI; CBV-weighted fMRI; Rat brain atlas; Neuroimaging; Forepaw stimulation ID FUNCTIONAL MRI; CBV RESPONSES; BRAIN; BOLD; REGISTRATION; STIMULATION; VALIDATION; TEMPLATE; SURGERY; ATLAS AB The value of analyzing neuroimaging data on a group level has been well established in human studies. However, there is no standard procedure for registering and analyzing functional magnetic resonance imaging (fMRI) data into common space in rodent fMRI studies. An approach for performing rat imaging data analysis in the stereotaxic framework is presented. This method is rooted in the biological observation that the skull shape and size of rat brain are essentially the same as long as their weights are within certain range. Registration is performed using rigid-body transformations without scaling or shearing, preserving the unique properties of the stable shape and size inherent in rat brain structure. Also, it does not require brain tissue masking and is not biased towards surface coil sensitivity profile. A standard rat brain atlas is used to facilitate the identification of activated areas in common space, allowing accurate region of interest analysis. This technique is evaluated from a group of rats (n=11) undergoing routine MRI scans; the registration accuracy is estimated to be within 400 gm. The analysis of fMRI data acquired with an electrical forepaw stimulation model demonstrates the utility of this technique. The method is implemented within the Analysis of Functional NeuroImages (AFNI) framework and can be readily extended to other studies. Published by Elsevier Inc. C1 [Lu, Hanbing; Scholl, Clara A.; Zuo, Yantao; Demny, Steven; Rea, William; Stein, Elliot A.; Yang, Yihong] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. RP Lu, HB (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. EM luha@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health FX The authors thank Dr. J. B. Mandeville at the Massachusetts General Hospital and Dr. A. C. Silva at the National Institute of Neurological Disease and Stroke for valuable discussions. This work was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 23 TC 16 Z9 16 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JAN PY 2010 VL 28 IS 1 BP 146 EP 152 DI 10.1016/j.mri.2009.05.019 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 583BX UT WOS:000276648600017 PM 19608368 ER PT J AU Hernando, D Kellman, P Haldar, JP Liang, ZP AF Hernando, Diego Kellman, P. Haldar, J. P. Liang, Z-P. TI Robust Water/Fat Separation in the Presence of Large Field Inhomogeneities Using a Graph Cut Algorithm SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE water/fat; graph cut; field map; cardiac MRI; Dixon ID FAT DECOMPOSITION; EXACT OPTIMIZATION; DIXON TECHNIQUE; MAP ESTIMATION; RECONSTRUCTION; SEARCH; PRIORS; HEART AB Water/fat separation is a classical problem for in vivo proton MRI. Although many methods have been proposed to address this problem, robust water/fat separation remains a challenge, especially in the presence of large amplitude of static field inhomogeneities. This problem is challenging because of the nonuniqueness of the solution for an isolated voxel. This paper tackles the problem using a statistically motivated formulation that jointly estimates the complete field map and the entire water/fat images. This formulation results in a difficult optimization problem that is solved effectively using a novel graph cut algorithm, based on an iterative process where all voxels are updated simultaneously. The proposed method has good theoretical properties, as well as an efficient implementation. Simulations and in vivo results are shown to highlight the properties of the proposed method and compare it to previous approaches. Twenty-five cardiac datasets acquired on a short, wide-bore scanner with different slice orientations were used to test the proposed method, which produced robust water/fat separation for these challenging datasets. This paper also shows example applications of the proposed method, such as the characterization of intramyocardial fat. Magn Reson Med 63:79-90, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Hernando, Diego; Haldar, J. P.; Liang, Z-P.] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Hernando, Diego; Haldar, J. P.; Liang, Z-P.] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Kellman, P.] NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hernando, D (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, 405 N Mathews Ave, Urbana, IL 61801 USA. EM dhernan2@illinois.edu RI Haldar, Justin/B-4983-2008 OI Haldar, Justin/0000-0002-1838-0211 FU [NTH-P41-RR023953-01]; [NIH-P41-EB001977-21]; [NSF-CBET-07-30623] FX The work presented in this paper was supported in part by the following research grants: NTH-P41-RR023953-01, NIH-P41-EB001977-21 and NSF-CBET-07-30623. We acknowledge the use of the Matlab Boost Graph Library (MatlabBGL) package, Written by David Gleich. NR 46 TC 83 Z9 83 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2010 VL 63 IS 1 BP 79 EP 90 DI 10.1002/mrm.22177 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 543LI UT WOS:000273578600010 PM 19859956 ER PT B AU McGlynn, KA Cook, MB AF McGlynn, Katherine A. Cook, Michael B. BE Foulkes, WD Cooney, KA TI The Epidemiology of Testicular Cancer SO MALE REPRODUCTIVE CANCERS: EPIDEMIOLOGY, PATHOLOGY AND GENETICS SE Cancer Genetics-Series LA English DT Article; Book Chapter ID GERM-CELL TUMORS; ENVIRONMENTAL RISK-FACTORS; MATERNAL HORMONE-LEVELS; CARCINOMA-IN-SITU; UPSTATE NEW-YORK; UNITED-STATES; PHYSICAL-ACTIVITY; BODY-SIZE; INCREASING INCIDENCE; TESTIS CANCER C1 [McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. RP McGlynn, KA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,Suite 550, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov NR 272 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0448-5 J9 CANCER GENET-SER JI Cancer Genetics PY 2010 BP 51 EP 83 DI 10.1007/978-1-4419-0449-2_2 D2 10.1007/978-1-4419-0449-2 PG 33 WC Oncology SC Oncology GA BNK26 UT WOS:000274787300002 ER PT B AU Osuch, JR Bonham, VL AF Osuch, Janet R. Bonham, Vence L. BE Jatoi, I Kaufmann, M TI Medicolegal Pitfalls in Breast Cancer Diagnosis and Management SO MANAGEMENT OF BREAST DISEASES LA English DT Article; Book Chapter ID SURVIVAL; MALPRACTICE; PHYSICIANS; SYMPTOMS; SURGEONS; THERAPY; SEEKING; WOMEN; DELAY C1 [Osuch, Janet R.] Michigan State Univ, E Lansing, MI 48824 USA. [Bonham, Vence L.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Osuch, JR (reprint author), Michigan State Univ, 632W Fee Hall, E Lansing, MI 48824 USA. EM janet.osuch@hc.msu.edu NR 51 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-69742-8 PY 2010 BP 645 EP 658 DI 10.1007/978-3-540-69743-5_33 D2 10.1007/978-3-540-69743-5 PG 14 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA BNL35 UT WOS:000274860000033 ER PT B AU Shiloach, J Rinas, U AF Shiloach, Joseph Rinas, Ursula BE Baltz, RH Davies, JE Demain, AL TI Bacterial Cultivation for Production of Proteins and Other Biological Products SO MANUAL OF INDUSTRIAL MICROBIOLOGY AND BIOTECHNOLOGY, THIRD EDITION LA English DT Article; Book Chapter ID RECOMBINANT ESCHERICHIA-COLI; HIGH-CELL-DENSITY; HIGH-LEVEL PRODUCTION; FED-BATCH; HETEROLOGOUS PROTEIN; HUMAN INSULIN; CULTURES; GROWTH; SCALE; AMORPHA-4,11-DIENE C1 [Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Rinas, Ursula] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany. RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. NR 39 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-512-7 PY 2010 BP 132 EP 144 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BOC33 UT WOS:000276164600012 ER PT S AU Chiariello, M Vaque, JP Crespo, P Gutkind, JS AF Chiariello, Mario Vaque, Jose P. Crespo, Piero Gutkind, J. Silvio BE Seger, R TI Activation of Ras and Rho GTPases and MAP Kinases by G-Protein-Coupled Receptors SO MAP KINASE SIGNALING PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Kinase assays; Western blot; Phosphorylation; Synthetic ligands; RASSLs; ERKs; GTP; Ras ID PATHWAYS AB A complex intracellular signaling network mediates the multiple biological activities of G-protein-coupled receptors (GPCRs). Among them, monomeric GTPases and a family of closely related proline-targeted serine threonine kinases, collectively known as Mitogen-Activated Protein Kinases (MAPKs), appears to play central roles in orchestrating the proliferative responses to multiple mitogens that act on GPCRs. Upon GDP/GTP exchange, monomeric GTPases control the phosphorylation of conserved threonine and tyrosine residues in MAPKs by their immediate upstream kinases, increasing their enzymatic activity and inducing their translocation to the nucleus where they phosphorylate transcription factors, thereby regulating the expression of genes playing a key role in normal and aberrant cell growth. Recently, a number of GPCRs have been engineered to provide exclusive activation by synthetic drug-like compounds while becoming insensitive to endogenous ligands. These engineered receptors, named Receptors Activated Solely by Synthetic Ligands (RASSLs), promise better understanding of GPCRs signaling in vitro and in vivo, thus representing ideal tools to selectively modulate MAPK signaling routes controlling a wide range of biological functions, from proliferation to differentiation, migration, invasion, and cell survival or death by apoptosis. C1 [Chiariello, Mario] Ist Toscano Tumori & Consiglio, Siena, Italy. [Crespo, Piero] Univ Cantabria, Inst Biomed & Biotecnol Cantabria IBBTEC, CSIC, IDICAN,Dept Biol Mol,Fac Med, E-39005 Santander, Cantabria, Spain. [Vaque, Jose P.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Chiariello, M (reprint author), Ist Toscano Tumori & Consiglio, Siena, Italy. RI Crespo, Piero/M-3273-2014; Chiariello, Mario/O-3642-2014; Vaque, Jose/H-8413-2015 OI Crespo, Piero/0000-0003-2825-7783; Chiariello, Mario/0000-0001-8434-5177; Vaque, Jose/0000-0002-3913-2495 NR 8 TC 10 Z9 10 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-794-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 661 SI 2nd BP 137 EP 150 DI 10.1007/978-1-60761-795-2_8 D2 10.1007/978-1-60761-795-2 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQY31 UT WOS:000282103400008 PM 20811981 ER PT S AU McKay, MM Morrison, DK AF McKay, Melissa M. Morrison, Deborah K. BE Seger, R TI Proteomic Analysis of Scaffold Proteins in the ERK Cascade SO MAP KINASE SIGNALING PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE ERK cascade scaffolds; Scaffold binding partners; Proteomics; Mass spectrometry; Affinity purification; Pyo/Glu-Glu tag ID T-ANTIGEN; KINASE; ACTIVATION; KSR1 AB ERK cascade scaffolds serve as docking platforms to coordinate the assembly of multiprotein complexes that contribute to the spatial and temporal control of ERK signaling. Given that protein protein interactions are essential for scaffold function, determining the full repertoire of scaffold binding partners will likely provide new insight into the regulation and activities of the ERK cascade scaffolds. In this chapter, we describe methods to identify scaffold interacting proteins using a proteomics approach. This protocol is based on the affinity purification of scaffold complexes from tissue culture cells and utilizes mass spectrometry to identify the protein constituents of the complex. C1 [McKay, Melissa M.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD 21701 USA. RP McKay, MM (reprint author), NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD 21701 USA. FU Intramural NIH HHS [ZIA BC011107-03] NR 17 TC 2 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-794-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 661 SI 2nd BP 323 EP 334 DI 10.1007/978-1-60761-795-2_19 D2 10.1007/978-1-60761-795-2 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQY31 UT WOS:000282103400019 PM 20811992 ER PT S AU Woods, AS Jackson, SN AF Woods, Amina S. Jackson, Shelley N. BE Rubakhin, SS Sweedler, JV TI The Application and Potential of Ion Mobility Mass Spectrometry in Imaging MS with a Focus on Lipids SO MASS SPECTROMETRY IMAGING: PRINCIPLES AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE MALDI; ion mobility; lipids; imaging; peptides; drugs; profiling ID DIRECT TISSUE-ANALYSIS; MALDI; LIPIDOMICS; TOFMS; PHOSPHOLIPIDS; SEPARATION AB Tissue profiling and imaging by MALDI mass spectrometry has allowed the direct analysis and localization of biomolecules in tissue. However, due to the in situ nature of this technique, the complexity of tissue, and the need for a chemical matrix in MALDI, the signal recorded can be extremely complex and difficult to assign. Combining ion mobility with matrix-assisted laser desorption/ionization is a very powerful technique for fast separation and analysis of biomolecules in complex mixtures (such as tissue and cells), as isobaric lipid, peptide, and oligonuclcotide molecular ions are pre-separated in the mobility cell before mass analysis. Differences in drift time of as much as 30% are obtained in a timescale of hundreds of microseconds. Molecular ions of the same biochemical family fall along trend lines when plotted in 2D plots of mobility drift time as a function of m/z. In this chapter ion mobility MALDI-MS ability to analyze various biomolecules in tissue, that is, lipids and proteins, as well as its ability to separate species from all of the major phospholipid classes from tissue and extracts, the effects that radyl chain length, degree of unsaturation, head group composition have upon their ion's cross section in the gas phase, and how it can be used not only to distinguish them from other biochemical groups in a mixture but also to differentiate them from other lipid species will be illustrated. C1 [Woods, Amina S.; Jackson, Shelley N.] Natl Inst Drug Abuse, Struct Biol Unit, Cellular Neurobiol Branch, Intramural Res Program,NIH, Baltimore, MD USA. RP Woods, AS (reprint author), Natl Inst Drug Abuse, Struct Biol Unit, Cellular Neurobiol Branch, Intramural Res Program,NIH, Baltimore, MD USA. FU Intramural NIH HHS [Z99 DA999999] NR 21 TC 15 Z9 15 U1 1 U2 13 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-745-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 656 BP 99 EP 111 DI 10.1007/978-1-60761-746-4_5 D2 10.1007/978-1-60761-746-4 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQJ72 UT WOS:000281188000005 PM 20680586 ER PT B AU Raju, TNK AF Raju, Tonse N. K. BE Zimmerman, AW Connors, SL TI Brave New World: The Intrauterine Environment as the Biological Foundation for the Lifespan SO MATERNAL INFLUENCES ON FETAL NEURODEVELOPMENT: CLINICAL AND RESEARCH ASPECTS LA English DT Article; Book Chapter DE Developmental origins of adult diseases; Fetal behavior; Fetal programming; Maternal hypothyroxinemia; Maternal-fetal interface; Perinatal encephalopathy C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Raju, TNK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Rm 4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-920-8 PY 2010 BP 1 EP 8 DI 10.1007/978-1-60327-921-5_1 D2 10.1007/978-1-60327-921-5 PG 8 WC Pediatrics SC Pediatrics GA BRC26 UT WOS:000282337700001 ER PT B AU Cantor, D Bonah, C AF Cantor, David Bonah, Christian BE Cantor, D Bonah, C Dorries, M TI INTRODUCTION: MEAT, MEDICINE, AND HUMAN HEALTH IN THE TWENTIETH CENTURY SO MEAT, MEDICINE AND HUMAN HEALTH IN THE TWENTIETH CENTURY SE Studies for the Society for the Social History of Medicine LA English DT Proceedings Paper CT Workshop on Meat, Medicine and Human Health in the Twentieth Century CY NOV 14-15, 2006 CL Washington, DC SP U S Natl Lib Med, Univ Strasbourg, Inst Rech Sci Technol, Univ Strasbourg, Med Fac, Maison InterUniv Sci l Homme Alsace ID WORLD-WAR-II; PERNICIOUS-ANEMIA; SHORT HISTORY; NUTRITIONAL SCIENCE; UNITED-STATES; SPONGIFORM ENCEPHALOPATHY; BOVINE TUBERCULOSIS; CANCER CONTROL; BELLE-EPOQUE; DISEASE C1 [Cantor, David] NIH, Off Hist, Bethesda, MD 20892 USA. [Bonah, Christian] Univ Strasbourg, Hist Med & Hlth Sci, Strasbourg, France. RP Cantor, D (reprint author), NIH, Off Hist, Bldg 10, Bethesda, MD 20892 USA. NR 784 TC 0 Z9 0 U1 1 U2 2 PU PICKERING & CHATTO PUBL PI LONDON PA 21 BLOOMSBURY WAY, LONDON, WC1A 2TH, ENGLAND BN 978-1-317-32320-4; 978-1-84893-103-9 J9 STUD SOC SOC HIST ME PY 2010 IS 1 BP 1 EP + PG 72 WC History & Philosophy Of Science SC History & Philosophy of Science GA BD8MF UT WOS:000364105100001 ER PT B AU Cantor, D AF Cantor, David BE Cantor, D Bonah, C Dorries, M TI CONFUSED MESSAGES: MEAT, CIVILIZATION, AND CANCER EDUCATION IN THE EARLY TWENTIETH CENTURY. SO MEAT, MEDICINE AND HUMAN HEALTH IN THE TWENTIETH CENTURY SE Studies for the Society for the Social History of Medicine LA English DT Proceedings Paper CT Workshop on Meat, Medicine and Human Health in the Twentieth Century CY NOV 14-15, 2006 CL Washington, DC SP U S Natl Lib Med, Univ Strasbourg, Inst Rech Sci Technol, Univ Strasbourg, Med Fac, Maison InterUniv Sci l Homme Alsace C1 NIH, Off Hist, Bethesda, MD 20892 USA. RP Cantor, D (reprint author), NIH, Off Hist, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PICKERING & CHATTO PUBL PI LONDON PA 21 BLOOMSBURY WAY, LONDON, WC1A 2TH, ENGLAND BN 978-1-317-32320-4; 978-1-84893-103-9 J9 STUD SOC SOC HIST ME PY 2010 IS 1 BP 111 EP 126 PG 16 WC History & Philosophy Of Science SC History & Philosophy of Science GA BD8MF UT WOS:000364105100007 ER PT J AU Levine, RL Bohr, VA AF Levine, Rodney L. Bohr, Vilhelm A. TI Earl R. Stadtman Appreciation SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Biographical-Item C1 [Levine, Rodney L.] NHLBI, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2010 VL 131 IS 1 BP 1 EP 1 DI 10.1016/j.mad.2009.12.003 PG 1 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 560ZU UT WOS:000274945300001 PM 20036277 ER PT J AU Viteri, G Chung, YW Stadtman, ER AF Viteri, Gabriela Chung, Youn Wook Stadtman, Earl R. TI Effect of progerin on the accumulation of oxidized proteins in fibroblasts from Hutchinson Gilford progeria patients SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Progeria; Aging; Proteasome; Oxidized proteins; ATP ID OXIDATIVE STRESS; PROTEASOME; CELLS; APOPTOSIS; UBIQUITIN; DISEASES; ANTIOXIDANTS; DEGRADATION; SENESCENCE; SURVIVAL AB The mutation responsible for Hutchinson Gilford Progeria Syndrome (HGPS) causes abnormal nuclear morphology Previous studies show that free radicals and reactive oxygen species play major roles in the etiology and/or progression of neurodegenerative diseases and aging. This study compares oxidative stress responses between progeric and normal fibroblasts Our data revealed higher ROS levels in HGPS cells compared to age-matched controls In response to oxidative challenge, progeric cells showed increased mRNA levels for mitochondrial superoxide dismutase (SOD) and SOD protein content However, this did not prevent a drop in the ATP content of progeria fibroblasts Previous studies have shown that declines in human fibroblast ATP levels interfere with programmed cell death and promote necrotic inflammation Notably, in Our investigations the ATP content of progeria fibroblasts was only similar to 50% of that found in healthy controls Furthermore, HGPS fibroblast analysis revealed a decrease in total caspase-like proteasome activity and in the levels of two active proteolytic complex subunits (beta(5) and beta(7)). A number of studies indicate that the molecular mechanisms causing accelerated aging in progeric patients also occur in healthy cells of older individuals. Thus, the results of this study may also help explain some of the cellular changes that accompany normal aging Published by Elsevier Ireland Ltd. C1 [Viteri, Gabriela; Chung, Youn Wook; Stadtman, Earl R.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2351,50 South Dr,MSC 8012, Bethesda, MD 20892 USA. FU Intramural Research Program of the National Heart, Lung, and Blood Institute FX We thank the members of the Laboratory of Biochemistry, National Heart, Lung, and Blood Institute for valuable suggestions during the course of this study The MEFs used in this study were kindly shared by Dr. Kan Cao and Mr. Michael Erdos, respectively, from the Molecular Genetics Section of the National Human Genome Research Institute. Marcy Stone provided guidance in the editing of the manuscript. Our special thanks to Dr. Rodney Levine for valuable discussions and comments. This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute. NR 37 TC 30 Z9 32 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2010 VL 131 IS 1 BP 2 EP 8 DI 10.1016/j.mad.2009.11.006 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 560ZU UT WOS:000274945300002 PM 19958786 ER PT J AU Chen, J Li, J Lim, FC Wu, Q Douek, DC Scott, DK Ravussin, E Hsu, HC Jazwinski, SM Mountz, JD AF Chen, Jian Li, Jun Lim, Fei Chu Wu, Qi Douek, Daniel C. Scott, Donald K. Ravussin, Eric Hsu, Hui-Chen Jazwinski, S. Michal Mountz, John D. CA Louisiana Healthy Aging Study TI Maintenance of naive CD8 T cells in nonagenarians by leptin, IGFBP3 and T3 SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Nonagenarians; Naive CD8; TREC; IGFBP3; Leptin; T3 ID RECENT THYMIC EMIGRANTS; RECEPTOR EXCISION CIRCLES; FACTOR-BINDING PROTEIN-3; HEMATOPOIETIC STEM-CELL; IMMUNE-SYSTEM; HUMAN LONGEVITY; AGE; EXPRESSION; IMMUNOSENESCENCE; APOPTOSIS AB Research into the age-associated decline in the immune system has focused on the factors that contribute to the accumulation of senescent CD8 T cells. Less attention has been paid to the non-immune factors that may maintain the pool of naive CD8 T cells. Here, we analyzed the status of the naive CD8 T-cell Population in healthy nonagenarians (>= 90-year-old), old (60-79-year-old), and young (20-34-year-old) subjects Naive CD8 T cells were defined as CD28(+)CD95(-) as this phenotype showed a strong co-expression of the CD45RA(+), CD45RO(-), and CD 127(+) phenotypes. Although there was an age-associated decline in the percentage of CD28(+)CD95(-)CD8 T cells, the healthy nonagenarians maintained a pool of naive CD28(+)CD95(-) cells that contained T-cell receptor excision circles (TREC)(+) cells The percentages of naive CD28(+)CD95(-) CD8 T cells in the nonagenarians correlated with the sera levels of insulin-like growth factor binding protein 3 (IGFBP3) and leptin Higher levels of triiodothyronine (T3) negatively correlated with the accumulation of TREC(-)CD28(-)CD95(+) CD8 T cells from nonagenarians These results Suggest a model in which IGFBP3. leptin and T3 act as non-immune factors to maintain a larger pool of naive CD8 T cells in healthy nonagenarians Published by Elsevier Ireland Ltd. C1 [Mountz, John D.] Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Douek, Daniel C.] NIH, Vaccine Res Ctr, Bethesda, MD USA. [Scott, Donald K.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Jazwinski, S. Michal] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, 1825 Univ Blvd,Room 307 Shelby Bldg, Birmingham, AL 35294 USA. RI Ermolao, Andrea/I-5463-2012 FU NIH/NIA [PO1 AG022064-01A1]; Millennium Trust [HEF(2001-06)-02] FX This research was supported by NIH/NIA PO1 AG022064-01A1 and by the Louisiana Board of Regents through the Millennium Trust Health Excellence Fund [HEF(2001-06)-02] We thank the Recruitment and Clinical Testing Core at the Pennington Biomedical Research Center for collecting the blood samples and the Sampling and Data Management Core at Louisiana State University Health Sciences Center for storage, quality control, and analyses of the data presented herein We thank Dr. David Allison for providing advice on Statistical Analysis. We also acknowledge Ms. Enid Keyser and at the Rheumatic Diseases Core Center - Analytic and Preparative Flow Cytometry Facility at University of Alabama-Birmingham for operating the FACS instrument, Dr. Fiona Hunter for expert edition of the manuscript, and Ms. Carol Humber for excellent secretarial assistance. NR 59 TC 19 Z9 20 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2010 VL 131 IS 1 BP 29 EP 37 DI 10.1016/j.mad.2009.11.003 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 560ZU UT WOS:000274945300005 PM 19941883 ER PT J AU Lee, SL Huang, PY Roller, P Cho, EG Park, D Dickson, RB AF Lee, Sheau-Ling Huang, Pao-Yi Roller, Peter Cho, Eun-Gyung Park, Dongeun Dickson, Robert B. TI Matriptase/epithin participates in mammary epithelial cell growth and morphogenesis through HGF activation SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Mammary epithelial; HGF/SF; SFTI; Epithelial modeling; ECMatrix; q-PCR; siRNA; EpH4 ID TRANSMEMBRANE SERINE-PROTEASE; FACTOR SCATTER FACTOR; BREAST-CANCER CELLS; IN-VITRO; PLASMINOGEN ACTIVATORS; PROTEOLYTIC CLEAVAGE; C-MET; HEPATOCYTE; EXPRESSION; UROKINASE AB The epithelial-derived, type II transmembrane serine protease matriptase, the mouse homologue of which is epithin, has been shown to be involved in epidermal differentiation, hair formation, and thymus function. We show in this study that epithin/matriptase (Epi/MTP) plays a significant role in mammary epithelial cell growth and morphogenesis. Epi/MTP is expressed at low level in the mouse mammary epithelium of young animals and it accumulates at the terminal end-bud of the growing ducts. The level of Epi/MTP is elevated in the mammary glands at stages when epithelial proliferation and modeling occur. It is primarily present in the luminal epithelial cells of mouse mammary ducts and lobules. Using an ex vivo three-dimensional culture system for mammary epithelial functional assays, we show that mammary epithelial growth and morphogenesis in the presence of the latent form hepatocyte growth factor (pro-HGF) are blocked either by an inhibitor of the Epi/MTP protease activity or by siRNA knockdown of the Epi/MTP expression. These studies demonstrate that Epi/MTP participates in mammary epithelial growth and modeling through activation of pro-HGF. Our findings reveal an important pathway in normal mammary epithelial morphogenesis which may participate in breast cancer progression. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Lee, Sheau-Ling; Huang, Pao-Yi] Natl Hlth Res Inst, Inst Cellular & Syst Med, Zhunan Town 35053, Miaoli County, Taiwan. [Dickson, Robert B.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. [Roller, Peter] NCI, Med Chem Lab, NIH, Frederick, MD 21701 USA. [Cho, Eun-Gyung; Park, Dongeun] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea. RP Lee, SL (reprint author), Natl Hlth Res Inst, Inst Cellular & Syst Med, Res Bldg 2,Rm 1027,35 Keyan Rd, Zhunan Town 35053, Miaoli County, Taiwan. EM sllee@nhri.org.tw FU National Health Research Institutes, Taiwan, ROC [SC-094-PP-03] FX We thank Dr. Michael Johnson for the valuable discussion in completion of this study. We also thank Dr. Gloria Chepko for editorial assistance. This work is supported by National Health Research Institutes Grant SC-094-PP-03 (S.-L.L.), Taiwan, ROC. NR 51 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JAN-FEB PY 2010 VL 127 IS 1-2 BP 82 EP 95 DI 10.1016/j.mod.2009.10.004 PG 14 WC Developmental Biology SC Developmental Biology GA 558ED UT WOS:000274722700008 PM 19853659 ER PT S AU Weisburger, EK AF Weisburger, Elizabeth K. BE Coppola, D TI Chemical Carcinogenesis Role of Chloroform - Further Studies SO MECHANISMS OF ONCOGENESIS: AN UPDATE ON TUMORIGENESIS SE Cancer Growth and Progression LA English DT Article; Book Chapter ID REGENERATIVE CELL-PROLIFERATION; FEMALE B6C3F(1) MICE; MALE F344 RATS; CANCER-RISK ASSESSMENT; OSBORNE-MENDEL RATS; DRINKING-WATER; CORN-OIL; LIVER-INJURY; INDUCED HEPATOTOXICITY; CARBON-TETRACHLORIDE C1 [Weisburger, Elizabeth K.] NCI, Div Canc Etiol, Rockville, MD 20850 USA. NR 74 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-3238 BN 978-90-481-3724-4 J9 CANCER GROW PROG-DOR JI Cancer Growth Prog.-Dordr. PY 2010 VL 12 BP 63 EP 69 DI 10.1007/978-90-481-3725-1_4 D2 10.1007/978-90-481-3725-1 PG 7 WC Oncology SC Oncology GA BQP62 UT WOS:000281482600004 ER PT S AU Mark, HFL Raimondi, SC Sokolic, R AF Mark, Hon Fong L. Raimondi, Susana C. Sokolic, Robert BE Coppola, D TI Chromosomal Abnormalities in Selected Hematopoietic Malignancies Detected by Conventional and Molecular Cytogenetics: Diagnostic and Prognostic Significance SO MECHANISMS OF ONCOGENESIS: AN UPDATE ON TUMORIGENESIS SE Cancer Growth and Progression LA English DT Article; Book Chapter ID ACUTE LYMPHOBLASTIC-LEUKEMIA; IN-SITU HYBRIDIZATION; ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; WORLD-HEALTH-ORGANIZATION; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION C1 [Mark, Hon Fong L.] Boston Univ, Sch Med, Cytogenet Labs, Boston, MA 02118 USA. [Raimondi, Susana C.] St Jude Childrens Hosp, Dept Pathol, Cytogenet Lab, Memphis, TN 38105 USA. [Sokolic, Robert] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Mark, HFL (reprint author), Brown Univ, KRAM Corp, Warren Alpert Med Sch, Providence, RI 02912 USA. EM HonFong_Mark@brown.edu NR 168 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1871-3238 BN 978-90-481-3724-4 J9 CANCER GROW PROG-DOR JI Cancer Growth Prog.-Dordr. PY 2010 VL 12 BP 89 EP 113 DI 10.1007/978-90-481-3725-1_6 D2 10.1007/978-90-481-3725-1 PG 25 WC Oncology SC Oncology GA BQP62 UT WOS:000281482600006 ER PT J AU Ecelbarger, CM Rash, A Sinha, RK Tiwari, S AF Ecelbarger, Carolyn M. Rash, Arjun Sinha, Rajesh K. Tiwari, Swasti TI The Effect of Chronic Candesartan Therapy on the Metabolic Profile and Renal Tissue Cytokine Levels in the Obese Zucker Rat SO MEDIATORS OF INFLAMMATION LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; II TYPE-1 RECEPTOR; DIABETIC-NEPHROPATHY; INSULIN SENSITIVITY; GLUCOSE-METABOLISM; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; INDUCED INFLAMMATION; INTERLEUKIN-18; COMPLICATIONS AB The effect of candesartan, an angiotensin-II type-1 receptor antagonist, on the metabolic profile and renal inflammation is unclear. We evaluated this relationship by feeding male lean (LZ) and obese (OZ) Zucker rats chow or chow with candesartan (23.5mg/kg . diet) for 14 weeks (n = 6-8/treatment/body type). Candesartan reduced serum triglycerides, plasma creatinine, urine albumin, and renal cortical collagen and glycogen deposition in the OZ. An ELISA-based cytokine array revealed that candesartan normalized elevated renal interleukin (IL) 1-beta and monocyte chemoattractant protein-1 (MCP-1) levels in OZ. Nonetheless, candesartan impaired glucose tolerance, and did not lower blood insulin or glucose levels. Moreover, renal IL-1 alpha, -2, -4, -6 and -10 tumor necrosis factor-alpha, interferon-gamma, were significantly reduced in OZ relative to LZ, and increased by candesartan. Furthermore, candesartan increased growth-regulated oncogene, transforming growth factor-beta 1 and IL-18 in OZ kidneys to a level higher than LZ or untreated OZ. Candesartan did not affect renal cytokine levels in LZ. Overall, candesartan attenuated renal disease and improved renal function in OZ, despite mixed effects on metabolic factors and cytokines. Reduced plasma triglycerides and/or renal MCP-1 and IL-1 beta may have had a role in this protection. However, these effects were clearly independent of any improvement in glucose tolerance. C1 [Ecelbarger, Carolyn M.; Rash, Arjun; Tiwari, Swasti] Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20057 USA. [Sinha, Rajesh K.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Tiwari, S (reprint author), Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20057 USA. EM st285@georgetown.edu FU National Institutes of Health [HL073193]; American Heart Association; National Capital Area National Kidney Foundation; Haddad Family Research funds FX This work was supported by the National Institutes of Health ( Grant no. HL073193) and an Established Investigator Award from the American Heart Association ( to C. M. Ecelbarger) and a National Capital Area National Kidney Foundation grant and Haddad Family Research funds ( to S. Tiwari). NR 59 TC 4 Z9 4 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2010 AR 841343 DI 10.1155/2010/841343 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 607NQ UT WOS:000278511200001 ER PT S AU Rahman, MM Antani, SK Long, RL Demner-Fushman, D Thoma, GR AF Rahman, Md. Mahmudur Antani, Sameer K. Long, Rodney L. Demner-Fushman, Dina Thoma, George R. BE Caputo, B Muller, H SyedaMahmood, T Duncan, JS Wang, F KalpathyCramer, J TI Multi-modal Query Expansion Based on Local Analysis for Medical Image Retrieval SO MEDICAL CONTENT-BASED RETRIEVAL FOR CLINICAL DECISION SUPPORT SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 1st MICCAI International Workshop on Medical Content-Based Retrieval for Clinical Decision Support CY SEP 20, 2009 CL London, ENGLAND SP MICCAI, IBM Almaden Res Ctr ID SYSTEMS AB A unified medical image retrieval framework integrating visual and text keywords using a novel multi-modal query expansion (QE) is presented. For the content-based image search, visual keywords are modeled using support vector machine (SVM)-based classification of local color and texture patches from image regions. For the text-based search, keywords from the associated annotations are extracted and indexed. The correlations between the keywords in both the visual and text feature spaces are analyzed for QE by considering local feedback information. The QE approach can propagate user perceived semantics from one modality to another and improve retrieval effectiveness when combined in multi-modal search. An evaluation of the method on imageCLEFmed'08 dataset and topics results in a mean average precision (MAP) score of 0.15 over comparable searches without QE or using only single modality. C1 [Rahman, Md. Mahmudur; Antani, Sameer K.; Long, Rodney L.; Demner-Fushman, Dina; Thoma, George R.] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Rahman, MM (reprint author), NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM rahmanmm@mail.nih.gov; santani@mail.nih.gov; rlong@mail.nih.gov; ddemner@mail.nih.gov; gthoma@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 NR 16 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-11768-8 J9 LECT NOTES COMPUT SC PY 2010 VL 5853 BP 110 EP 119 PG 10 WC Computer Science, Information Systems; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BPD33 UT WOS:000278559600011 ER PT J AU Chahla, M Eberlein, M Wright, S AF Chahla, Mayy Eberlein, Michael Wright, Scott TI The effect of providing a USB syllabus on resident reading of landmark articles SO MEDICAL EDUCATION ONLINE LA English DT Article DE medical education; electronic syllabus; USB drive AB Background: The acquisition of new knowledge is a primary goal of residency training. Retrieving and retaining influential primary and secondary medical literature can be challenging for house officers. We set out to investigate the effect of a Universal Serial Bus (USB) drive loaded with landmark scientific articles on housestaff education in a pilot study. Methods: We created a USB syllabus that contains 187 primary scientific research articles. The electronic syllabus had links to the full-text articles and was organized using an html webpage with a table of contents according to medical subspecialties. We performed a prospective cohort study of 53 house officers in the internal medicine residency program who received the USB syllabus. We evaluated the impact of the USB syllabus on resident education with surveys at the beginning and conclusion of the nine-month study period. Results: All 50 respondents (100%) reported to have used the USB syllabus. The self-reported number of original articles read each month was higher at the end of the nine-month study period compared to baseline. Housestaff rated original articles as being a more valuable educational resource after the intervention. Conclusions: An electronic syllabus with landmark scientific articles placed on a USB drive was widely utilized by housestaff, increased the self-reported reading of original scientific articles and seemed to have positively influenced residents' attitude toward original medical literature. C1 [Chahla, Mayy; Wright, Scott] Johns Hopkins Univ, Sch Med, Div Hosp Med, Baltimore, MD 21218 USA. [Eberlein, Michael] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Eberlein, Michael] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. [Wright, Scott] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. RP Chahla, M (reprint author), Johns Hopkins Univ, Sch Med, Div Hosp Med, Baltimore, MD 21218 USA. EM mchahla1@jhmi.edu; eberleinmh@cc.nih.gov NR 11 TC 1 Z9 1 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1087-2981 J9 MED EDUC ONLINE JI Med. Educ. Online PY 2010 VL 15 AR 4639 DI 10.3402/meo.v15i0.4639 PG 5 WC Education & Educational Research SC Education & Educational Research GA V28SG UT WOS:000208699900003 ER PT J AU Parascandola, M AF Parascandola, Mark TI Cancer in the twentieth century SO MEDICAL HISTORY LA English DT Book Review C1 [Parascandola, Mark] NCI, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NCI, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0025-7273 J9 MED HIST JI Med. Hist. PD JAN PY 2010 VL 54 IS 1 BP 122 EP 123 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 549UM UT WOS:000274079800012 ER PT J AU Becker, KG Schultz, ST AF Becker, Kevin G. Schultz, Stephen T. TI Similarities in features of autism and asthma and a possible link to acetaminophen use SO MEDICAL HYPOTHESES LA English DT Article ID MIGRATION INHIBITORY FACTOR; SPECTRUM DISORDER; IMMUNE-RESPONSE; PARACETAMOL USE; MAST-CELLS; GENETIC POLYMORPHISMS; FACTOR MIF; CHILDREN; RISK; PREVALENCE AB Autism and autism spectrum disorders are enigmatic conditions that have their origins in the interaction of genes and environmental factors. In this hypothesis, genes statistically associated with autism are emphasized to be important in inflammation and in innate immune pathways, including pathways for susceptibility to asthma. The role of acetaminophen (paracetamol) in an increased risk for asthma is described and a possible similar link to an increased risk for autism is suggested. (C) Published by Elsevier Ltd. C1 [Becker, Kevin G.] NIA, Biomed Res Ctr, NIH, Gene Express & Genom Unit, Baltimore, MD 21224 USA. [Schultz, Stephen T.] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, N Chicago, IL 60064 USA. RP Becker, KG (reprint author), NIA, Biomed Res Ctr, NIH, Gene Express & Genom Unit, Suite 100,Room 4B122,251 Bayview Blvd, Baltimore, MD 21224 USA. EM beckerk@grc.nia.nih.gov OI Becker, Kevin/0000-0002-6794-6656 FU NIH, National Institute on Aging, National Institutes of Health FX This research was supported by the intramural Research Program of the NIH, National Institute on Aging, National Institutes of Health. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. NR 85 TC 26 Z9 28 U1 2 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JAN PY 2010 VL 74 IS 1 BP 7 EP 11 DI 10.1016/j.mehy.2009.08.033 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 547VU UT WOS:000273918500003 PM 19748189 ER PT S AU Geng, XJ Gu, H Shin, WY Ross, TJ Yang, YH AF Geng, Xiujuan Gu, Hong Shin, Wanyong Ross, Thomas J. Yang, Yihong BE Jiang, T Navab, N Pluim, JPW Viegever, MA TI Group-Wise Diffeomorphic Diffusion Tensor Image Registration SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2010, PT I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 13th International Conference on Medical Image Computing and Computer-Assisted Intervention CY SEP 20-24, 2010 CL China Natl Convent Ctr, Beijing, PEOPLES R CHINA SP MICCAI Soc HO China Natl Convent Ctr ID ATLAS CONSTRUCTION; MRI AB We propose an unbiased group-wise diffeomorphic registration technique to normalize a group of diffusion tensor (DT) images. Our method uses an implicit reference group-wise registration framework to avoid bias caused by reference selection. Log-Euclidean metrics on diffusion tensors are used for the tensor interpolation and computation of the similarity cost functions. The overall energy function is constructed by a diffeomorphic demons approach. The tensor reorientation is performed and implicitly optimized during the registration procedure. The performance of the proposed method is compared with reference-based diffusion tensor imaging (DTI) registration methods. The registered DTI images have smaller shape differences in terms of reduced variance of the fractional anisotropy maps and more consistent tensor orientations. We demonstrate that fiber tract atlas construction can benefit from the group-wise registration by producing fiber bundles with higher overlaps. C1 [Geng, Xiujuan; Gu, Hong; Shin, Wanyong; Ross, Thomas J.; Yang, Yihong] Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Geng, XJ (reprint author), Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. EM gengx@nida.nih.gov OI Ross, Thomas/0000-0002-7745-3572 NR 22 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-15704-2 J9 LECT NOTES COMPUT SC PY 2010 VL 6361 BP 598 EP 606 PG 9 WC Computer Science, Software Engineering; Computer Science, Theory & Methods; Neuroimaging; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Neurosciences & Neurology; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BTS19 UT WOS:000287946100073 ER PT S AU Wang, Y Resnick, SM Davatzikos, C AF Wang, Ying Resnick, Susan M. Davatzikos, Christos BE Jiang, T Navab, N Pluim, JPW Viergever, MA TI Spatio-temporal Analysis of Brain MRI Images Using Hidden Markov Models SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2010, PT II, SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 13th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 20-24, 2010 CL China Natl Convent Ctr, Beijing, PEOPLES R CHINA SP MICCAI Soc HO China Natl Convent Ctr ID CLASSIFICATION; PATTERN; SCANS; MCI AB A rapidly increasing number of medical imaging studies is longitudinal, i.e. involves series of repeated examinations of the same individuals. This paper presents a methodology for analysis of such 4D images, with brain aging as the primary application. An adaptive regional clustering method is first adopted to construct a spatial pattern, in which a measure of correlation between morphological measurements and a continuous patient's variable (age in our case) is used to group brain voxels into regions; Secondly, a dynamic probabilistic Hidden Markov Model (HMM) is created to statistically analyze the relationship between spatial brain patterns and hidden states; Thirdly, parametric HMM models under a bagging framework are used to capture the changes occurring with time by decoding the hidden states longitudinally. We apply this method to datasets from elderly individuals, and test the effectiveness of this spatio-temporal model in analyzing the temporal dynamics of spatial aging patterns on an individual basis. Experimental results show this method could facilitate the early detection of pathological brain change. C1 [Wang, Ying; Davatzikos, Christos] Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA. [Resnick, Susan M.] NIA, Lab Personal & Cognit, Baltimore, MD USA. RP Wang, Y (reprint author), Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA. NR 16 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-15744-8 J9 LECT NOTES COMPUT SC PY 2010 VL 6362 BP 160 EP + PG 3 WC Computer Science, Software Engineering; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BTR11 UT WOS:000287828300020 ER PT S AU Liu, JF Subramanian, KR Yoo, TS AF Liu, Jianfei Subramanian, Kalpathi R. Yoo, Terry S. BE Jiang, T Navab, N Pluim, JPW Viergever, MA TI Region Flow: A Multi-stage Method for Colonoscopy Tracking SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2010, PT II, SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 13th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 20-24, 2010 CL China Natl Convent Ctr, Beijing, PEOPLES R CHINA SP MICCAI Soc HO China Natl Convent Ctr DE colonoscopy; tracking; failure recovery; image matching ID REGISTRATION; SCALE AB Co-located optical and virtual colonoscopy images provide important clinical information during routine colonoscopy procedures. Tracking algorithms that rely on image features to align virtual and optical images can fail when they encounter blurry image sequences. This is a common occurrence in colonoscopy images, when the endoscope touches a wall or is immersed in fluid. We propose a region-flow based matching algorithm to determine the large changes between images that bridge such interruptions in the visual field. The region flow field is used as the means to limit the search space for computing corresponding feature points; a sequence of refining steps is performed to identify the most reliable and accurate feature point pairs. The feature point pairs are then used in a deformation based scheme to compute the final camera parameters. We have successfully tested this algorithm on four clinical colonoscopy image sequences containing anywhere from 9-57 consecutive blurry images. Two additional tabletop experiments were performed to quantitatively validate the algorithm: the endoscope was moved along a slightly curved path by 24 mm and along a straight path by 40 mm. Our method reported errors within 1-5% in these experiments. C1 [Liu, Jianfei; Subramanian, Kalpathi R.] Univ N Carolina, Dept Comp Sci, Charlotte, NC 28223 USA. [Yoo, Terry S.] NIH, Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20892 USA. RP Liu, JF (reprint author), Univ N Carolina, Dept Comp Sci, Charlotte, NC 28223 USA. EM jliu1@uncc.edu; krs@uncc.edu; yoo@nlm.nih.gov NR 12 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-15744-8 J9 LECT NOTES COMPUT SC PY 2010 VL 6362 BP 505 EP + PG 3 WC Computer Science, Software Engineering; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BTR11 UT WOS:000287828300062 ER PT S AU Linguraru, MG Pura, JA Chowdhury, AS Summers, RM AF Linguraru, Marius George Pura, John A. Chowdhury, Ananda S. Summers, Ronald M. BE Jiang, T Navab, N Pluim, JPW Viergever, MA TI Multi-organ Segmentation from Multi-phase Abdominal CT via 4D Graphs Using Enhancement, Shape and Location Optimization SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2010, PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 13th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY SEP 20-24, 2010 CL China Natl Convent Ctr, Beijing, PEOPLES R CHINA SP MICCAI Soc HO China Natl Convent Ctr DE multi-phase CT; segmentation; 4D graph; shape; enhancement ID IMAGES; CONSTRUCTION AB The interpretation of medical images benefits from anatomical and physiological priors to optimize computer-aided diagnosis (CAD) applications. Diagnosis also relies on the comprehensive analysis of multiple organs and quantitative measures of soft tissue. An automated method optimized for medical image data is presented for the simultaneous segmentation of four abdominal organs from 4D CT data using graph cuts. Contrast-enhanced CT scans were obtained at two phases: non-contrast and portal venous. Intra-patient data were spatially normalized by non-linear registration. Then 4D erosion using population historic information of contrast-enhanced liver, spleen, and kidneys was applied to multi-phase data to initialize the 4D graph and adapt to patient specific data. CT enhancement information and constraints on shape, from Parzen windows, and location, from a probabilistic atlas, were input into a new formulation of a 4D graph. Comparative results demonstrate the effects of appearance and enhancement, and shape and location on organ segmentation. C1 [Linguraru, Marius George; Pura, John A.; Chowdhury, Ananda S.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Linguraru, MG (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM lingurarum@mail.nih.gov NR 16 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-15710-3 J9 LECT NOTES COMPUT SC PY 2010 VL 6363 BP 89 EP 96 PG 8 WC Computer Science, Software Engineering; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BTS17 UT WOS:000287945600012 ER PT S AU Guan, HY Antani, S Long, LR Thoma, GR AF Guan, Haiying Antani, Sameer Long, L. Rodney Thoma, George R. BE Liu, BJ Boonn, WW TI Minimizing the Semantic Gap in Biomedical Content-Based Image Retrieval SO MEDICAL IMAGING 2010: ADVANCED PACS-BASED IMAGING INFORMATICS AND THERAPEUTIC APPLICATIONS SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Advanced PACS-based Imaging Informatics and Therapeutic Applications CY FEB 17-18, 2010 CL San Diego, CA SP SPIE, Medtronic Inc, Aeroflex Inc, Tungsten Heavy Powder Inc DE Content-Based Image Retrieval; NHANES II database; Ranking SVM; semantic gap; shape retrieval; digital radiography ID PATTERN-RECOGNITION; SHAPES; GRAPHS AB A major challenge in biomedical Content-Based Image Retrieval (CBIR) is to achieve meaningful mappings that minimize the semantic gap between the high-level biomedical semantic concepts and the low-level visual features in images. This paper presents a comprehensive learning-based scheme toward meeting this challenge and improving retrieval quality. The article presents two algorithms: a learning-based feature selection and fusion algorithm and the Ranking Support Vector Machine (Ranking SVM) algorithm. The feature selection algorithm aims to select 'good' features and fuse them using different similarity measurements to provide a better representation of the high-level concepts with the low-level image features. Ranking SVM is applied to learn the retrieval rank function and associate the selected low-level features with query concepts, given the ground-truth ranking of the training samples. The proposed scheme addresses four major issues in CBIR to improve the retrieval accuracy: image feature extraction, selection and fusion, similarity measurements, the association of the low-level features with high-level concepts, and the generation of the rank function to support high-level semantic image retrieval. It models the relationship between semantic concepts and image features, and enables retrieval at the semantic level. We apply it to the problem of vertebra shape retrieval from a digitized spine x-ray image set collected by the second National Health and Nutrition Examination Survey (NHANES II). The experimental results show an improvement of up to 41.92% in the mean average precision (MAP) over conventional image similarity computation methods. C1 [Guan, Haiying; Antani, Sameer; Long, L. Rodney; Thoma, George R.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. RP Guan, HY (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. EM guanh@mail.nih.gov; santani@mail.nih.gov; rlong@mail.nih.gov; gthoma@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 NR 24 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8029-3 J9 P SOC PHOTO-OPT INS PY 2010 VL 7628 AR 762807 DI 10.1117/12.844470 PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK56 UT WOS:000284752500005 ER PT S AU Xue, ZY Antani, S Long, LR Thoma, GR AF Xue, Zhiyun Antani, Sameer Long, L. Rodney Thoma, George R. BE Liu, BJ Boonn, WW TI Web-accessible cervigram automatic segmentation tool SO MEDICAL IMAGING 2010: ADVANCED PACS-BASED IMAGING INFORMATICS AND THERAPEUTIC APPLICATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Advanced PACS-based Imaging Informatics and Therapeutic Applications CY FEB 17-18, 2010 CL San Diego, CA SP SPIE, Medtronic Inc, Aeroflex Inc, Tungsten Heavy Powder Inc DE image segmentation; system development; uterine cervix image ID IMAGES AB Uterine cervix image analysis is of great importance to the study of uterine cervix cancer, which is among the leading cancers affecting women worldwide. In this paper, we describe our proof-of-concept, Web-accessible system for automated segmentation of significant tissue regions in uterine cervix images, which also demonstrates our research efforts toward promoting collaboration between engineers and physicians for medical image analysis projects. Our design and implementation unifies the merits of two commonly used languages, MATLAB and Java. It circumvents the heavy workload of recoding the sophisticated segmentation algorithms originally developed in MATLAB into Java while allowing remote users who are not experienced programmers and algorithms developers to apply those processing methods to their own cervicographic images and evaluate the algorithms. Several other practical issues of the systems are also discussed, such as the compression of images and the format of the segmentation results. C1 [Xue, Zhiyun; Antani, Sameer; Long, L. Rodney; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Xue, ZY (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 23 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8029-3 J9 PROC SPIE PY 2010 VL 7628 AR 76280Z DI 10.1117/12.844336 PG 8 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Medical Informatics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK56 UT WOS:000284752500033 ER PT S AU Matsuda, KM Chung, JY Ylaya, K Dodd, S Fukunaga, M Hewitt, SM AF Matsuda, Kant M. Chung, Joon-Yong Ylaya, Kris Dodd, Steve Fukunaga, Masaki Hewitt, Stephen M. BE Molthen, RC Weaver, JB TI Microscopic resolution imaging and proteomics correlation at histogeographically identical location: Point by point correlation between ex vivo tissue imaging with high field MRI and multiplex tissue immunoblotting for proteomics profiling SO MEDICAL IMAGING 2010: BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Biomedical Applications in Molecular, Structural, and Functional Imaging CY FEB 14-16, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, Tungsten Heavy Powder, Inc AB Histopathologic correlation is an essential component for validation of the radiological findings. There has been significant advancement in medical imaging technologies, including molecular imaging, such that, it is essential to establish the system beyond histopathologic correlation, to protein profiling that can be correlated with imaging at anatomically identical manner for accurate examination. Recently, a novel technology for proteomic profiling has been established, called "multiplex tissue immunoblotting (MTIB)" which can offer studying multiple protein expression from a single histology slide. Therefore, we attempted to establish the system to obtain an identical plane between high resolution imaging and histopathology at microscopic level so that proteomic profiling can be readily performed using MTIB. A variety of tissues were obtained from autopsy materials and initially scanned with high field MRI (14T) ex vivo along with the marker for tissue orientation. The histology slides were prepared from post-scanned tissue under the marker-guidance in order to obtain an identical plane with high resolution imaging. Subsequently, MTIB was carried out to study expression of proteins of interest and point by point correlation with high resolution imaging was performed at histogeographically identical manner. C1 [Matsuda, Kant M.; Ylaya, Kris; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Gaithersburg, MD 20877 USA. RP Matsuda, KM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, NIH, 8712 Grovemont Circle, Gaithersburg, MD 20877 USA. OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8027-9 J9 P SOC PHOTO-OPT INS PY 2010 VL 7626 AR 76262B DI 10.1117/12.854966 PG 7 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK57 UT WOS:000284752800074 ER PT S AU Aman, JM Yao, JH Summers, RM AF Aman, Javed M. Yao, Jianhua Summers, Ronald M. BE Karssemeijer, N Summers, RM TI Prediction of Polyp Histology on CT Colonography Using Content-Based Image Retrieval SO MEDICAL IMAGING 2010: COMPUTER - AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Computer-Aided Diagnosis CY FEB 16-18, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, Tungsten Heavy Powder, Inc DE CT Colonography; CAD; Content-Based Image Retrieval; Polyp Histology ID ADENOMATOUS POLYPS; POLYPECTOMY; CANCER; COLON AB Predicting the malignancy of colonic polyps is a difficult problem and in general requires an invasive polypectomy procedure. We present a less-invasive and automated method to predict the histology of colonic polyps under computed tomographic colonography (CTC) using the content-based image retrieval (CBIR) paradigm. For the purpose of simplification, polyps annotated as hyperplastic or "other benign" were classified as benign polyps (BP) and the rest (adenomas and cancers) were classified as malignant polyps (MP). The CBIR uses numerical feature vectors generated from our CTC computer aided detection (CTC-CAD) system to describe the polyps. These features relate to physical and visual characteristics of the polyp. A representative database of CTC-CAD polyp images is created. Query polyps are matched with those in the database and the results are ranked based on the similarity to the query. Polyps with a majority of representative MPs in their result set are predicted to be malignant and similarly those with a majority of BPs in their results are benign. For evaluation, the system is compared to the typical optical colonoscopy (OC) size based classification. Using receiver operating curve (ROC) analysis, we show our system is sufficiently better than the OC size method. C1 [Aman, Javed M.; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Aman, JM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8025-5 J9 PROC SPIE PY 2010 VL 7624 AR 76240D DI 10.1117/12.844571 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK55 UT WOS:000284752400011 ER PT S AU Chen, XJ Udupa, JK Alavi, A Torigian, DA AF Chen, Xinjian Udupa, Jayaram K. Alavi, Abass Torigian, Drew A. BE Karssemeijer, N Summers, RM TI Pathology Detection on Medical Images Based on Oriented Active Appearance Models SO MEDICAL IMAGING 2010: COMPUTER - AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Computer-Aided Diagnosis CY FEB 16-18, 2010 CL San Diego, CA SP SPIE, Medtronic Inc, Aeroflex Inc, Tungsten Heavy Powder, Inc DE Object Recognition; Pattern Recognition; Segmentation; Active Appearance Models; CAD ID LESION DETECTION; SHAPE MODELS; SEGMENTATION; ALGORITHMS AB In this paper, we propose a novel, general paradigm based on creating a statistical geographic model of shape and appearance of normal body regions. Any deviations from the normality information captured in a given patient image are highlighted and expressed as a fuzzy pathology image. We study the feasibility of this idea in 2D images via Oriented Active Appearance Models (OAAM). The OAAM synergistically combines AAM and live-wire concepts. The approach consists of three main stages: model building, segmentation, and pathology detection. The model is built utilizing image data from normal subjects. The model currently includes shape and texture information. A variety of other information (functional, morphometric) can be added in the future. For segmentation, a novel automatic object recognition method is proposed which strategically combines the AAM with the live-wire method. A two level dynamic programming method is used to do the finer delineation. During the process of segmentation, a multi-object strategy is used for improving recognition and delineation accuracy. For pathology detection, the model is first fit to the given image as best as possible via recognition and delineation of the objects included in the model. Subsequently, a fuzzy pathology image is generated that expresses deviations in appearance of the given image form the texture information contained in the model. The proposed method was tested on two clinical CT medical image datasets each consisting of 40 images. Our preliminary results indicate high segmentation accuracy (TPVF>97%, FPVF<0.5%) for delineating objects by the multi-object strategy with good pathology detection results suggesting the feasibility of the proposed system. C1 [Chen, Xinjian] NIH, Diag Radiol Dept, Ctr Clin, Bethesda, MD 20814 USA. RP Chen, XJ (reprint author), NIH, Diag Radiol Dept, Ctr Clin, Bethesda, MD 20814 USA. EM chenx6@mail.nih.gov NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8025-5 J9 PROC SPIE PY 2010 VL 7624 AR 76243M DI 10.1117/12.844543 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK55 UT WOS:000284752400120 ER PT S AU Liu, JM White, JM Summers, RM AF Liu, Jiamin White, Jacob M. Summers, Ronald M. BE Karssemeijer, N Summers, RM TI Computer-aided Lymph Node Detection in Abdominal CT Images SO MEDICAL IMAGING 2010: COMPUTER - AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Computer-Aided Diagnosis CY FEB 16-18, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, Tungsten Heavy Powder, Inc DE lymph node detection; 3D blob detector; Hessian matrix; object scale ID SEGMENTATION AB Many malignant processes cause abdominal lymphadenopathy, and computed tomography (CT) has become the primary modality for its detection. A lymph node is considered enlarged (swollen) if it is more than 1 centimeter in diameter. Which lymph nodes are swollen depends on the type of disease and the body parts involved. Identifying their locations is very important to determine the possible cause. In the current clinical workflow, the detection and diagnosis of enlarged lymph nodes is usually performed manually by examining all slices of CT images, which can be error-prone and time consuming. 3D blob enhancement filter is a usual way for computer-aided node detection. We proposed a new 3D blob detector for automatic lymph node detection in contrast-enhanced abdominal CT images. Since lymph nodes are usually next to blood vessels, abdominal blood vessels were first segmented as a reference to set the search region for lymph nodes. Then a new detection response measure, blobness, is defined based on eigenvalues of the Hessian matrix and the object scale in our new blob detector. Voxels with higher blobness were clustered as lymph node candidates. Finally some prior anatomical knowledge was utilized for false positive reduction. We applied our method to 5 patients and compared the results with the performance of the original blobness definition. Both methods achieved sensitivity of 83.3% but the false positive rates per patient were 14 and 26 for our method and the original method, respectively. Our results indicated that computer-aided lymph node detection with this new blob detector may yield a high sensitivity and a relatively low FP rate in abdominal CT. C1 [Liu, Jiamin; White, Jacob M.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Liu, JM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10,Room 1C368X,MSC 1182, Bethesda, MD 20892 USA. NR 14 TC 2 Z9 2 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8025-5 J9 PROC SPIE PY 2010 VL 7624 AR 76240U DI 10.1117/12.844406 PG 7 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK55 UT WOS:000284752400028 ER PT S AU Wang, QA Charisi, A Latecki, LJ Gee, J Megalooikonomou, V AF Wang, Qiang Charisi, Amalia Latecki, Longin Jan Gee, James Megalooikonomou, Vasileios BE Karssemeijer, N Summers, RM TI Shape Similarity Analysis of Regions of Interest in Medical Images SO MEDICAL IMAGING 2010: COMPUTER - AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Computer-Aided Diagnosis CY FEB 16-18, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, Tungsten Heavy Powder, Inc DE Shape representation; sequence similarity; optimal subsequence bijection; dynamic time warping; shape analysis; corpus callosum ID CORPUS-CALLOSUM; REPRESENTATION AB In this work, we introduce a new representation technique of 2D contour shapes and a sequence similarity measure to characterize 2D regions of interest in medical images. First, we define a distance function on contour points in order to map the shape of a given contour to a sequence of real numbers. Thus, the computation of shape similarity is reduced to the matching of the obtained sequences. Since both a query and a target sequence may be noisy, i.e., contain some outlier elements, it is desirable to exclude the outliers in order to obtain a robust matching performance. For the computation of shape similarity, we propose the use of an algorithm which performs elastic matching of two sequences. The contribution of our approach is that, unlike previous works that require images to be warped according to a template image for measuring their similarity, it obviates this need, therefore it can estimate image similarity for any type of medical image in a fast and efficient manner. To demonstrate our method's applicability, we analyzed a brain image dataset consisting of corpus callosum shapes, and we investigated the structural differences between children with chromosome 22q11.2 deletion syndrome and controls. Our findings indicate that our method is quite effective and it can be easily applied on medical diagnosis in all cases of which shape difference is an important clue. C1 [Wang, Qiang] NIAID, NIH, Bethesda, MD 20892 USA. RP Wang, QA (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM wangq2@mail.nih.gov NR 18 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8025-5 J9 PROC SPIE PY 2010 VL 7624 AR 762428 DI 10.1117/12.844319 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK55 UT WOS:000284752400076 ER PT S AU Wang, SJ Yao, JH Petrick, N Summers, RM AF Wang, Shijun Yao, Jianhua Petrick, Nicholas Summers, Ronald M. BE Karssemeijer, N Summers, RM TI Matching Colonic Polyps Using Correlation Optimized Warping SO MEDICAL IMAGING 2010: COMPUTER - AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Computer-Aided Diagnosis CY FEB 16-18, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, Tungsten Heavy Powder, Inc DE Computed Tomographic Colonography; colonic polyp matching; correlation optimized warping; normalized distance along the colon centerline ID CT COLONOGRAPHY; COLONOSCOPY; POPULATION AB Computed tomographic colonography (CTC) combined with a computer aided detection system has the potential for improving colonic polyp detection and increasing the use of CTC for colon cancer screening. In the clinical use of CTC, a true colonic polyp will be confirmed with high confidence if a radiologist can find it on both the supine and prone scans. To assist radiologists in CTC reading, we propose a new method for matching polyp findings on the supine and prone scans. The method performs a colon registration using four automatically identified anatomical salient points and correlation optimized warping (COW) of colon centerline features. We first exclude false positive detections using prediction information from a support vector machine (SVM) classifier committee to reduce initial false positive pairs. Then each remaining CAD detection is mapped to the other scan using the COW technique applied to the distance along the centerline in each colon. In the last step, a new SVM classifier is applied to the candidate pair dataset to find true polyp pairs between supine and prone scans. Experimental results show that our method can improve the sensitivity to 0.87 at 4 false positive pairs per patient compared with 0.74 for a competing method that uses the normalized distance along the colon centerline (p<0.01). C1 [Wang, Shijun; Yao, Jianhua; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM rms@nih.gov; rms@nih.gov NR 10 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8025-5 J9 PROC SPIE PY 2010 VL 7624 AR 76240E DI 10.1117/12.844352 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSK55 UT WOS:000284752400012 ER PT S AU Sussman, DL Yao, JH Summers, RM AF Sussman, Daniel L. Yao, Jianhua Summers, Ronald M. BE Dawant, BM Haynor, DR TI Automated Fat Measurement and Segmentation with Intensity Inhomogeneity Correction SO MEDICAL IMAGING 2010: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Image Processing CY FEB 14-16, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc., Aeroflex, Inc., OpenXi, Tungsten Heavy Powder, Inc. DE Adipose tissue; segmentation; abdominal MRI; inhomogeneity correction ID SUBCUTANEOUS ADIPOSE-TISSUE; ABDOMINAL FAT; UNSUPERVISED ASSESSMENT; MR-IMAGES; BODY-FAT AB Adipose tissue (AT) content, especially visceral AT (VAT), is an important indicator for risks of many disorders, including heart disease and diabetes. Fat measurement by traditional means is often inaccurate and cannot separate subcutaneous and visceral fat. MRI offers a medium to obtain accurate measurements and segmentation between subcutaneous and visceral fat. We present an approach to automatically label the voxels associated with adipose tissue and segment them between subcutaneous and visceral. Our method uses non-parametric non-uniform intensity normalization (N3) to correct for image artifacts and inhomogeneities, fuzzy c-means to cluster AT regions and active contour models to separate SAT and VAT. Our algorithm has four stages: body masking, preprocessing, SAT and VAT separation, and tissue classification and quantification. The method was validated against a manual method performed by two observers, which used thresholds and manual contours to separate SAT and VAT. We measured 25 patients, 22 of which were included in the final analysis and the other three had too much artifact for automated processing. For SAT and total AT, differences between manual and automatic measurements were comparable to manual inter-observer differences. VAT measurements showed more variance in the automated method, likely due to inaccurate contours. C1 [Sussman, Daniel L.; Yao, Jianhua; Summers, Ronald M.] NIH, Bethesda, MD 20814 USA. RP Sussman, DL (reprint author), NIH, 10 Ctr Dr, Bethesda, MD 20814 USA. EM jyao@cc.nih.gov NR 17 TC 1 Z9 1 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8024-8 J9 PROC SPIE PY 2010 VL 7623 AR 76233X DI 10.1117/12.843860 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO04 UT WOS:000285048800134 ER PT S AU Zhuge, Y Udupa, JK Miller, RW AF Zhuge, Ying Udupa, Jayaram K. Miller, Robert W. BE Dawant, BM Haynor, DR TI Fuzzy Affinity Induced Curve Evolution SO MEDICAL IMAGING 2010: IMAGE PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Image Processing CY FEB 14-16, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc., Aeroflex, Inc., OpenXi, Tungsten Heavy Powder, Inc. DE Curve evolution; fuzzy affinity; image segmentation; level set; local scale ID GEODESIC ACTIVE CONTOURS; IMAGE SEGMENTATION; LEVEL SETS; ALGORITHMS AB In this paper, we present a fuzzy affinity induced curve evolution method for image segmentation without the need for solving PDEs, thereby making level set implementations vastly more efficient. We make use of fuzzy affinity that has been employed in fuzzy connectedness methods as a speed function for curve evolution. The fuzzy affinity consists of two components, namely homogeneity-based affinity and object-feature-based affinity, which take account both boundary gradient and object region information. Ball scale - a local morphometric structure - has been used for image noise suppression. We use a similar strategy for curve evolution as the method in, 1 but simplify the voxel switching mechanism where only one linked list is used to implicitly represent the evolving curve. We have presented several studies to evaluate the performance of the method based on brain MR and lung CT images. These studies demonstrate high accuracy and efficiency of the proposed method. C1 [Zhuge, Ying; Miller, Robert W.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Zhuge, Y (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhugey@mail.nih.gov; jay@mail.med.upenn.edu; rwmiller@mail.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8024-8 J9 PROC SPIE PY 2010 VL 7623 AR 76234A DI 10.1117/12.843793 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO04 UT WOS:000285048800147 ER PT S AU Chen, XJ Udupa, JK Bagci, U Alavi, A Torigian, DA AF Chen, Xinjian Udupa, Jayaram K. Bagci, Ulas Alavi, Abass Torigian, Drew A. BE Wong, KH Miga, MI TI 3D Automatic Anatomy Recognition Based on Iterative Graph-Cut-ASM SO MEDICAL IMAGING 2010: VISUALIZATION, IMAGE-GUIDED PROCEDURES, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Visualization, Image-Guided Procedures, and Modeling CY FEB 14-16, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, OpenXi, Tungsten Heavy Powder, Inc DE Object Recognition; Segmentation; Active Shape Models; Graph Cut ID ACTIVE SHAPE MODELS; IMAGE SEGMENTATION; ENERGY MINIMIZATION; FUZZY CONNECTEDNESS; OBJECT DEFINITION; PRIOR KNOWLEDGE; BRAIN MRI; ALGORITHMS AB We call the computerized assistive process of recognizing, delineating, and quantifying organs and tissue regions in medical imaging, occurring automatically during clinical image interpretation, automatic anatomy recognition (AAR). The AAR system we are developing includes five main parts: model building, object recognition, object delineation, pathology detection, and organ system quantification. In this paper, we focus on the delineation part. For the modeling part, we employ the active shape model (ASM) strategy. For recognition and delineation, we integrate several hybrid strategies of combining purely image based methods with ASM. In this paper, an iterative Graph-Cut ASM (IGCASM) method is proposed for object delineation. An algorithm called GC-ASM was presented at this symposium last year for object delineation in 2D images which attempted to combine synergistically ASM and GC. Here, we extend this method to 3D medical image delineation. The IGCASM method effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. We propose a new GC cost function, which effectively integrates the specific image information with the ASM shape model information. The proposed methods are tested on a clinical abdominal CT data set. The preliminary results show that: (a) it is feasible to explicitly bring prior 3D statistical shape information into the GC framework; (b) the 3D IGCASM delineation method improves on ASM and GC and can provide practical operational time on clinical images. C1 [Chen, Xinjian] NIH, Diag Radiol Dept, Ctr Clin, Bethesda, MD 20814 USA. RP Chen, XJ (reprint author), NIH, Diag Radiol Dept, Ctr Clin, Bethesda, MD 20814 USA. EM chenx6@mail.nih.gov OI Bagci, Ulas/0000-0001-7379-6829 NR 25 TC 0 Z9 0 U1 1 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8026-2 J9 PROC SPIE PY 2010 VL 7625 AR 76251T DI 10.1117/12.844551 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO02 UT WOS:000285047500063 ER PT S AU Li, M Mazilu, D Wood, BJ Horvath, KA Kapoor, A AF Li, Ming Mazilu, Dumitru Wood, Bradford J. Horvath, Keith A. Kapoor, Ankur BE Wong, KH Miga, MI TI A robotic assistant system for cardiac interventions under MRI guidance SO MEDICAL IMAGING 2010: VISUALIZATION, IMAGE-GUIDED PROCEDURES, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Visualization, Image-Guided Procedures, and Modeling CY FEB 14-16, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, OpenXi, Tungsten Heavy Powder, Inc DE Surgical system integration; compact fiducial; MRI compatible robot; real-time MRI guidance; aortic valve replacement ID PROSTATE INTERVENTIONS; FEASIBILITY; MANIPULATOR; TRACKING; DESIGN; SWINE; FIELD AB In this paper we present a surgical assistant system for implanting prosthetic aortic valve transapically under MRI guidance, in a beating heart. The system integrates an MR imaging system, a robotic system, as well as user interfaces for a surgeon to plan the procedure and manipulate the robot. A compact robotic delivery module mounted on a robotic arm is used for delivering both balloon-expandable and self-expanding prosthesis. The system provides different user interfaces at different stages of the procedure. A compact fiducial pattern close to the volume of interest is proposed for robot registration. The image processing and the transformation recovery methods using this fiducial in MRI are presented. The registration accuracy obtained by using this compact fiducial is comparable to the larger multi-spherical marker registration method. The registration accuracy using these two methods is less than 0.62 +/- 0.50 deg (mean +/- std. dev.) and 0.63 +/- 0.72 deg (mean +/- std. dev.), respectively. We evaluated each of the components and show that they can work together to form a complete system for transapical aortic valve replacement. C1 [Li, Ming; Mazilu, Dumitru; Horvath, Keith A.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Li, M (reprint author), NHLBI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lim2@mail.nih.gov NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8026-2 J9 PROC SPIE PY 2010 VL 7625 AR 76252X DI 10.1117/12.844458 PG 10 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO02 UT WOS:000285047500102 ER PT S AU Yao, JH Chowdhury, AS Summers, RM AF Yao, Jianhua Chowdhury, Ananda S. Summers, Ronald M. BE Wong, KH Miga, MI TI Realistic Colon Simulation in CT Colonography Using Mesh Skinning SO MEDICAL IMAGING 2010: VISUALIZATION, IMAGE-GUIDED PROCEDURES, AND MODELING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2010 - Visualization, Image-Guided Procedures, and Modeling CY FEB 14-16, 2010 CL San Diego, CA SP SPIE, Medtronic, Inc, Aeroflex, Inc, OpenXi, Tungsten Heavy Powder, Inc DE CT Colonography; Mesh Skinning; Colon Simulation ID COMPUTER-AIDED DETECTION; TOMOGRAPHIC VIRTUAL COLONOSCOPY; POLYP MEASUREMENT; PHANTOM; SEGMENTATION; MODEL; VISUALIZATION; ALGORITHM; SIZE; MAP AB Realistic colon simulations do not exist but would be valuable for CT colonography (CTC) CAD development and validation of new colon image processing algorithms. The human colon is a convoluted tubular structure and very hard to model physically and electronically. In this investigation, we propose a novel approach to generate realistic colon simulation using mesh skinning. The method proceeds as follows. First, a digital phantom of a cylindrical tube is modeled to simulate a straightened colon. Second, haustral folds and teniae coli are added to the cylindrical tube. Third, a centerline equipped with rotation-minimizing frames (RMF) and distention values is computed. Fourth, mesh skinning is applied to warp the tube around the centerline and generate realistic colon simulation. Lastly, colonic polyps in the shape of ellipsoids are also modeled. Results show that the simulated colon highly resembles the real colon. This is the first colon simulation that incorporates most colon characteristics in one model, including curved centerline, variable distention, haustral folds, teniae coli and colonic polyps. C1 [Yao, Jianhua; Chowdhury, Ananda S.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM jyao@cc.nih.gov NR 37 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8026-2 J9 PROC SPIE PY 2010 VL 7625 AR 76252J DI 10.1117/12.844224 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSO02 UT WOS:000285047500088 ER PT S AU Chen, XJ Summers, R Yao, JH AF Chen, Xinjian Summers, Ronald Yao, Jianhua BE Liao, HG Edwards, PJ Pan, XC Fan, Y Yang, GZ TI FEM Based 3D Tumor Growth Prediction for Kidney Tumor SO MEDICAL IMAGING AND AUGMENTED REALITY SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Medical Imaging and Augmented Reality CY SEP 19-20, 2010 CL China Natl Convent Ctr, Beijing, PEOPLES R CHINA SP Chinese Acad Sci, No Digital Inc, Siemens Corp Res, Translat Syst Biol & Med Initiat, Univ Tokyo HO China Natl Convent Ctr DE Tumor Growth Prediction; Finite Element Method; Segmentation; Kidney Tumor ID GLIOMA GROWTH; BRAIN-TUMORS; MODEL; DIFFUSION; DEFORMATION AB It is important to predict the tumor growth so that appropriate treatment can be planned especially in the early stage. In this paper, we propose a finite element method (FEM) based 3D tumor growth prediction system using longitudinal kidney tumor images. To the best of our knowledge, this is the first kidney tumor growth prediction system. The kidney tissues are classified into three types: renal cortex, renal medulla and renal pelvis. The reaction-diffusion model is applied as the tumor growth model. Different diffusion properties are considered in the model: the diffusion for renal medulla is considered as anisotropic, while those of renal cortex and renal pelvis are considered as isotropic. The FEM is employed to simulate the diffusion model. Automated estimation of the model parameters is performed via optimization of an objective function reflecting overlap accuracy, which is optimized in parallel via HOPSPACK (hybrid optimization parallel search). An exponential curve fitting based on the non-linear least squares method is used for multi-time point model parameters prediction. The proposed method was tested on the seven time points longitudinal kidney tumor CT studies from two patients with five tumors. The experimental results showed the feasibility and efficacy of the proposed method. C1 [Chen, Xinjian; Summers, Ronald; Yao, Jianhua] NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20814 USA. RP Chen, XJ (reprint author), NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20814 USA. EM chenx6@mail.nih.gov NR 22 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 978-3-642-15698-4 J9 LECT NOTES COMPUT SC PY 2010 VL 6326 BP 159 EP 168 PG 10 WC Computer Science, Theory & Methods; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BTD73 UT WOS:000286579700017 ER PT S AU Liu, XF Linguraru, MG Yao, JH Summers, RM AF Liu, Xiaofeng Linguraru, Marius George Yao, Jianhua Summers, Ronald M. BE Liao, HG Edwards, PJ Pan, XC Fan, Y Yang, GZ TI Organ Pose Distribution Model and an MAP Framework for Automated Abdominal Multi-organ Localization SO MEDICAL IMAGING AND AUGMENTED REALITY SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Medical Imaging and Augmented Reality CY SEP 19-20, 2010 CL China Natl Convent Ctr, Beijing, PEOPLES R CHINA SP Chinese Acad Sci, No Digital Inc, Siemens Corp Res, Translat Syst Biol & Med Initiat, Univ Tokyo HO China Natl Convent Ctr DE Organ localization; maximum a posteriori; probabilistic atlas; pose distribution model ID CT IMAGES; PROBABILISTIC ATLAS; SEGMENTATION; LIVER; CONSTRUCTION AB Abdominal organ localization is required as an initialization step for most automated abdominal organ analysis tasks, i.e. segmentation, registration, and computer aided-diagnosis. Automated abdominal organ localization is difficult because of the large variability of organ shapes, similar appearances of different organs in images, and organs in close proximity to each other. Previous methods predicted only the organ locations, but not the full organ poses including additionally sizes and orientations. Thus they were often not accurate enough to initialize other image analysis tasks. In this work we proposed a maximum a posteriori (MAP) framework to estimate the poses of multiple abdominal organs from non-contrast CT images. A novel organ pose distribution model is proposed to model the organ poses and limit the search space. Additionally the method uses probabilistic atlases for organ shapes, and Gaussian mixture models for organ intensity profile. An MAP problem is then formulated and solved for organ poses. The method was applied for the localization of liver, left and right kidneys, spleen, and pancreas, and showed promising results, especially on liver and spleen (with mean location and orientation errors under 5.3 mm and 7 degrees respectively). C1 [Liu, Xiaofeng; Linguraru, Marius George; Yao, Jianhua; Summers, Ronald M.] Natl Inst Hlth, Ctr Clin, Radiol & Imaging Sci, Imaging Biomarkers & Comp Aided Diag Lab, Bethesda, MD 20892 USA. RP Liu, XF (reprint author), Natl Inst Hlth, Ctr Clin, Radiol & Imaging Sci, Imaging Biomarkers & Comp Aided Diag Lab, Bethesda, MD 20892 USA. NR 16 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-15698-4 J9 LECT NOTES COMPUT SC PY 2010 VL 6326 BP 393 EP 402 PG 10 WC Computer Science, Theory & Methods; Engineering, Biomedical; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BTD73 UT WOS:000286579700041 ER PT J AU Cerliani, JP Giulianelli, S Sahores, A Wargon, V Gongora, A Baldi, A Molinol, A Lamb, CA Lanari, C AF Cerliani, Juan P. Giulianelli, Sebastian Sahores, Ana Wargon, Victoria Gongora, Adrian Baldi, Alberto Molinol, Alfredo Lamb, Caroline A. Lanari, Claudia TI MIFEPRISTONE INHIBITS MPA- AND FGF2-INDUCED MAMMARY TUMOR GROWTH BUT NOT FGF2-INDUCED MAMMARY HYPERPLASIA SO MEDICINA-BUENOS AIRES LA English DT Article DE breast cancer; mammary gland; mammary carcinomas; FGF2; progestins; RU486 ID CARCINOMA-ASSOCIATED FIBROBLASTS; BREAST-CANCER; PROGESTERONE-RECEPTORS; PREVENTION; MECHANISMS; INSIGHTS; FGFR2; MICE AB We have previously demonstrated a crosstalk between fibroblast growth factor 2 (FGF2) and progestins inducing experimental breast cancer growth. The aim of the present study was to compare the effects of FGF2 and of medroxyprogesterone acetate (MPA) on the mouse mammary glands and to investigate whether the antiprogestin RU486 was able to reverse the MPA- or FGF2-induced effects on both, mammary gland and tumor growth. We demonstrate that FGF2 administered locally induced an intraductal hyperplasia that was not reverted by RU486, suggesting that FGF2-induced effects are progesterone receptor (PR)-independent. However, MPA induced paraductal hyperplasia was reverted by RU486 and a partial agonistic effect was observed in RU486-treatad glands. Using C4-HD tumors which only grow in the presence of MPA, we showed that FGF2 administered intratumorally was able to stimulate tumor growth as MPA. The histology of FGF2-treated tumors showed different degrees of gland differentiation. RU486 inhibited both, MPA or FGF2 induced tumor growth. However, only complete regression was observed in MPA-treated tumors. Our results support the hypothesis that stromal FGF2 activates PR inducing hormone independent tumor growth. C1 [Cerliani, Juan P.; Giulianelli, Sebastian; Sahores, Ana; Gongora, Adrian; Baldi, Alberto; Lamb, Caroline A.; Lanari, Claudia] Consejo Nacl Invest Cient & Tecn, IBYME, Lab Carcinogenesis Hormonal, RA-1428 Buenos Aires, DF, Argentina. [Molinol, Alfredo] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Lanari, C (reprint author), Consejo Nacl Invest Cient & Tecn, IBYME, Lab Carcinogenesis Hormonal, Vuelta Obligado 2490, RA-1428 Buenos Aires, DF, Argentina. EM clanari@dna.uba.ar FU SECYT [PICTs 2005, 2007 932]; Fundacion Sales; Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA FX This work was supported by SECYT (PICTs 2005 and 2007 932 to C. Lanari); and Fundacion Sales. Dr. Molinolo is supported by the Intramural Research Program of the Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU MEDICINA (BUENOS AIRES) PI BUENOS AIRES PA DONATO ALVAREZ 3150, 1427 BUENOS AIRES, ARGENTINA SN 0025-7680 J9 MEDICINA-BUENOS AIRE JI Med.-Buenos Aires PY 2010 VL 70 IS 6 BP 529 EP 532 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 702KI UT WOS:000285892700009 PM 21163742 ER PT J AU Jain, J Kumar, Y Stables, J Sinha, R AF Jain, Jainendra Kumar, Y. Stables, James Sinha, Reema TI Menthone Semicarbazides and Thiosemicarbazides as Anticonvulsant Agents SO MEDICINAL CHEMISTRY LA English DT Article DE (+/-) 3-menthone; semicarbazides; thiosemicarbazides; anticonvulsant; Maximal Electroshock Seizure (MES); subcutaneous pentylene tetrazole (scPTZ); Antiepileptic drug development (AED) ID ANTIEPILEPTIC DRUG DEVELOPMENT; DERIVATIVES AB A series of novel (+/-) 3-menthone semicarbazides (1-7) and thiosemicarbazides (8-14) were synthesized using an appropriate synthetic route and characterized by thin layer chromatography and spectral analysis. The anticonvulsant activity of synthesized compounds was established after intraperitoneal administration in three seizure models in mice which include maximal electroshock seizure (MES), subcutaneous pentylene tetrazole (scPTZ) induced seizure and minimal neurotoxicity test. Seven compounds exhibited protection in both models and N(1) - (4-fluorophenyl) - N(4)- (menth-3-one) semicarbazide (4) emerged as the most active compound with MES ED(50) of 44.15mg/kg and scPTZ ED(50) of 38.68mg/kg at 0.25h duration. These compounds were found to elevate gamma-amino butyric acid (GABA) levels in the mid-brain region, thus indicating that (+/-) 3-menthone semicarbazides could be considered as a lead molecule in designing of a potent anticonvulsant drug. C1 [Jain, Jainendra; Sinha, Reema] Ram Eesh Inst Vocat & Tech Educ, Dept Pharm, Gautam Budh Nagar 201308, Uttar Pradesh, India. [Kumar, Y.] ITS Paramed Coll Pharm, Ghaziabad 201206, Uttar Pradesh, India. [Stables, James] NINDS, NIH, Bethesda, MD 20892 USA. RP Jain, J (reprint author), Ram Eesh Inst Vocat & Tech Educ, Dept Pharm, 3 Knowledge Pk 1, Gautam Budh Nagar 201308, Uttar Pradesh, India. EM jainendrem@yahoo.com NR 23 TC 10 Z9 10 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4064 J9 MED CHEM JI Med. Chem. PD JAN PY 2010 VL 6 IS 1 BP 44 EP 50 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 579VW UT WOS:000276405800007 PM 20402660 ER PT J AU Otto, M AF Otto, Michael TI Looking Tomard Basic Sciencefor Potential Drug Discovery Targets Against Community-Associated MRSA SO MEDICINAL RESEARCH REVIEWS LA English DT Article; Proceedings Paper CT Biotech Symposium held in honor of Roy Doi CY 2009 CL Georgia State Univ, Atlanta, GA HO Georgia State Univ DE community-associated methicillin-resistant Staphylococcus aureus; antibiotic resistance; virulence ID RESISTANT STAPHYLOCOCCUS-AUREUS; PANTON-VALENTINE LEUKOCIDIN; CASSETTE CHROMOSOME MEC; PEPTIDE-SENSING SYSTEM; TOXIC SHOCK SYNDROME; ANTIMICROBIAL PEPTIDES; VANCOMYCIN RESISTANCE; NASAL CARRIAGE; FITNESS COST; ALPHA-TOXIN AB The difficulties to find a conventional vaccine against Staphylococcus aureus and the increasing resistance of S. aureus to many antibiotics demand the exploration of novel therapeutic options, Such as by targeting virulence determinants and using specific antibodies in an antitoxin-like approach. Community-associated methicillin-resistant S. aureus (CA-MRSA) strains have recently emerged predominantly in the US, causing epidemic outbreaks of mostly skin and Soft tissue infections, but also more dramatic and sometimes fatal diseases. MRSA is now the most frequent cause of death by a single infectious agent in the US. The fact that, at least in the US, CA-MRSA infections are almost entirely due to one sequence type, USA300, gives researchers a novel, unique chance to focus Oil one clone in their efforts to analyze pathogenesis in a clinically important S. aureus. While the molecular underpinnings of the exceptional virulence and transmissibility of USA300 are not yet well understood, recent findings indicate that increased expression of widespread virulence determinants and acquisition of mobile genetic elements have to be considered. Delineating the relative importance of virulence determinants in USA300 and other important clinical strains is a key endeavor needed to develop a potential antitoxin for CA-MRSA disease. Published 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 1, 1-22, 2010 C1 NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Bldg 33 1W10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS [Z99 AI999999, Z01 AI000904-06] NR 128 TC 23 Z9 23 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD JAN PY 2010 VL 30 IS 1 BP 1 EP 22 DI 10.1002/med.20160 PG 22 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 541ZP UT WOS:000273460900001 PM 19399829 ER PT J AU Collins, FS AF Collins, Francis S. BE Rubenfeld, S TI THIS PAST MUST NOT BE PROLOGUE FOREWORD SO MEDICINE AFTER THE HOLOCAUST: FROM THE MASTER RACE TO THE HUMAN GENOME AND BEYOND LA English DT Editorial Material; Book Chapter C1 [Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PALGRAVE PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND BN 978-0-23010-229-3 PY 2010 BP XIX EP XXI D2 10.1057/9780230102293 PG 3 WC History & Philosophy Of Science; Medical Ethics SC History & Philosophy of Science; Medical Ethics GA BWM28 UT WOS:000294227500001 ER PT J AU DeBakey, ME AF DeBakey, Michael E. BE Rubenfeld, S TI MEDICINE AFTER THE HOLOCAUST FROM THE MASTER RACE TO THE HUMAN GENOME AND BEYOND AFTERWORD SO MEDICINE AFTER THE HOLOCAUST: FROM THE MASTER RACE TO THE HUMAN GENOME AND BEYOND LA English DT Editorial Material; Book Chapter C1 [DeBakey, Michael E.] Baylor Coll Med, Houston, TX 77030 USA. [DeBakey, Michael E.] Natl Lib Med, Bethesda, MD 20894 USA. RP DeBakey, ME (reprint author), Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PALGRAVE PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, ENGLAND BN 978-0-23010-229-3 PY 2010 BP 221 EP 223 D2 10.1057/9780230102293 PG 3 WC History & Philosophy Of Science; Medical Ethics SC History & Philosophy of Science; Medical Ethics GA BWM28 UT WOS:000294227500023 ER PT S AU Zeng-Treitler, Q Kim, H Rosemblat, G Keselman, A AF Zeng-Treitler, Qing Kim, Hyeoneui Rosemblat, Graciela Keselman, Alla BE Safran, C Reti, S Marin, HF TI Can Multilingual Machine Translation Help Make Medical Record Content More Comprehensible to Patients? SO MEDINFO 2010, PTS I AND II SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 13th World Congress on Medical and Health Informatics of International-Medical-Informatics-Association (Medinfo) CY SEP 12-15, 2010 CL Cape Town, SOUTH AFRICA SP Int Med Informat Assoc DE Comprehension; Translating; Consumer health information; Medical records ID LANGUAGE BARRIERS; HEALTH AB With the development of electronic personal health records, more patients are gaining access to their own medical records. However, comprehension of medical record content remains difficult for many patients. Because each record is unique, it is also prohibitively costly to employ human translators to solve this problem. In this study, we investigated whether multilingual machine translation could help make medical record content more comprehensible to patients who lack proficiency in the language of the records. We used a popular general-purpose machine translation tool called Babel Fish to translate 213 medical record sentences from English into Spanish, Chinese, Russian and Korean. We evaluated the comprehensibility and accuracy of the translation. The text characteristics of the incorrectly translated sentences were also analyzed. In each language, the majority of the translations were incomprehensible (76% to 92%) and/or incorrect (77% to 89%). The main causes of the translation are vocabulary difficulty and syntactical complexity. A general-purpose machine translation tool like the Babel Fish is not adequate for the translation of medical records; however, a machine translation tool can potentially be improved significantly, if it is trained to target certain narrow domains in medicine. C1 [Zeng-Treitler, Qing] Univ Utah, Dept Biomed Informat, 26 South 2000 East,Room 5775 HSEB, Salt Lake City, UT 84112 USA. [Kim, Hyeoneui] Univ Calif San Diego, Div Biomed Informat, Dept Med, San Diego, CA USA. [Rosemblat, Graciela; Keselman, Alla] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. RP Zeng-Treitler, Q (reprint author), Univ Utah, Dept Biomed Informat, 26 South 2000 East,Room 5775 HSEB, Salt Lake City, UT 84112 USA. EM q.t.zeng@utah.edu FU National Institute of Health (NIH) [R01 LM07222]; Intramural Research Program of the NIH; National Library of Medicine/Lister Hill National Center for Biomedical Communications FX This work is supported by the National Institute of Health (NIH) grant R01 LM07222 and by the Intramural Research Program of the NIH, National Library of Medicine/Lister Hill National Center for Biomedical Communications. NR 16 TC 5 Z9 5 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-588-4 J9 STUD HEALTH TECHNOL PY 2010 VL 160 BP 73 EP 77 DI 10.3233/978-1-60750-588-4-73 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BG8CS UT WOS:000392215900015 PM 20841653 ER PT S AU Bekhuis, T Demner-Fushman, D AF Bekhuis, Tanja Demner-Fushman, Dina BE Safran, C Reti, S Marin, HF TI Towards Automating the Initial Screening Phase of a Systematic Review SO MEDINFO 2010, PTS I AND II SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 13th World Congress on Medical and Health Informatics of International-Medical-Informatics-Association (Medinfo) CY SEP 12-15, 2010 CL Cape Town, SOUTH AFRICA SP Int Med Informat Assoc DE Artificial intelligence; Machine learning; Review literature as topic; Systematic review; Study characteristics [publication type]; Cochrane Oral Health Group AB Systematic review authors synthesize research to guide clinicians in their practice of evidence-based medicine. Teammates independently identify provisionally eligible studies by reading the same set of hundreds and sometimes thousands of citations during an initial screening phase. We investigated whether supervised machine learning methods can potentially reduce their workload. We also extended earlier research by including observational studies of a rare condition. To build training and test sets, we used annotated citations from a search conducted for an in-progress Cochrane systematic review. We extracted features from titles, abstracts, and metadata, then trained, optimized, and tested several classifiers with respect to mean performance based on 10-fold cross-validations. In the training condition, the evolutionary support vector machine (EvoSVM) with an Epanechnikov or radial kernel is the best classifier: mean recall=100%; mean precision=48% and 41%, respectively. In the test condition, EvoSVM performance degrades: mean recall=77%, mean precision ranges from 26% to 37%. Because near-perfect recall is essential in this context, we conclude that supervised machine learning methods may be useful for reducing workload under certain conditions. C1 [Bekhuis, Tanja] Univ Pittsburgh, Sch Dent Med, Ctr Dent Informat, 379 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. [Bekhuis, Tanja] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA USA. [Demner-Fushman, Dina] US Natl Lib Med, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. RP Bekhuis, T (reprint author), Univ Pittsburgh, Sch Dent Med, Ctr Dent Informat, 379 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. OI Bekhuis, Tanja/0000-0002-8537-9077 FU US National Library of Medicine (NLM) Research Participation Program; NLM; Oak Ridge Institute for Science and Education; NLM/NIDCR Pittsburgh Biomedical Informatics Training Program [5 T15 LM/DE07059-22] FX This research was supported, in part, by the US National Library of Medicine (NLM) Research Participation Program, sponsored by NLM and administered by the Oak Ridge Institute for Science and Education; and by the NLM/NIDCR Pittsburgh Biomedical Informatics Training Program 5 T15 LM/DE07059-22. We would like to thank Mr. Halil Kilicoglu and Mr. Matthew Simpson for technical support; Drs. Thankam Thyvalikakath and Richard Oliver for help with labeling citations; and Ms. Anne Littlewood, Cochrane Oral Health Group Trials Search Coordinator, for conducting the search for citations. NR 17 TC 9 Z9 10 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-588-4 J9 STUD HEALTH TECHNOL PY 2010 VL 160 BP 146 EP 150 DI 10.3233/978-1-60750-588-4-146 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BG8CS UT WOS:000392215900029 PM 20841667 ER PT S AU Fiszman, M Bray, BE Shin, D Kilicoglu, H Bennett, GC Bodenreider, O Rindflesch, TC AF Fiszman, Marcelo Bray, Bruce E. Shin, Dongwook Kilicoglu, Halil Bennett, Glen C. Bodenreider, Olivier Rindflesch, Thomas C. BE Safran, C Reti, S Marin, HF TI Combining Relevance Assignment with Quality of the Evidence to Support Guideline Development SO MEDINFO 2010, PTS I AND II SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 13th World Congress on Medical and Health Informatics of International-Medical-Informatics-Association (Medinfo) CY SEP 12-15, 2010 CL Cape Town, SOUTH AFRICA SP Int Med Informat Assoc DE Natural language processing; Machine learning; Clinical guidelines ID BIOMEDICAL TEXT; CLINICAL QUESTIONS; KNOWLEDGE; SYSTEM; UMLS AB Clinical practice guidelines are used to disseminate best practice to clinicians. Successful guidelines depend on literature that is both relevant to the questions posed and based on high quality research in accordance with evidence-based medicine. Meeting these standards requires extensive manual review. We describe a system that combines symbolic semantic processing with a statistical method for selecting both relevant and high quality studies. We focused on a cardiovascular risk factor guideline, and the overall performance of the system was 56% recall, 91% precision (F-0.5-score 0.81). If quality of the evidence is not taken into account, performance drops to 62% recall, 79% precision (F-0.5-score 0.75). We suggest that this system can potentially improve the efficiency of the literature review process in guideline development. C1 [Fiszman, Marcelo; Shin, Dongwook; Bodenreider, Olivier; Rindflesch, Thomas C.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Bennett, Glen C.] NHLBI, NIH, Bethesda, MD 20892 USA. [Bray, Bruce E.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA. [Kilicoglu, Halil] Concordia Univ, Dept Comp Sci & Software Engn, Montreal, PQ, Canada. RP Fiszman, M (reprint author), Natl Lib Med, 8600 Rockville Pike,Bldg 38A,Rm B1N-28J, Bethesda, MD 20894 USA. EM fiszmanm@mail.nih.gov FU National Library of Medicine; National Heart Lung and Blood Institute; Intramural Research Program of the National Institutes of Health, National Library of Medicine FX This study was supported in part through an interagency agreement between the National Library of Medicine and the National Heart Lung and Blood Institute and by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 20 TC 3 Z9 4 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-588-4 J9 STUD HEALTH TECHNOL PY 2010 VL 160 BP 709 EP 713 DI 10.3233/978-1-60750-588-4-709 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BG8CS UT WOS:000392215900140 PM 20841778 ER PT S AU Erdogan, H Erdem, E Bodenreider, O AF Erdogan, Halit Erdem, Esra Bodenreider, Olivier BE Safran, C Reti, S Marin, HF TI Exploiting UMLS Semantics for Checking Semantic Consistency among UMLS concepts SO MEDINFO 2010, PTS I AND II SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 13th World Congress on Medical and Health Informatics of International-Medical-Informatics-Association (Medinfo) CY SEP 12-15, 2010 CL Cape Town, SOUTH AFRICA SP Int Med Informat Assoc DE Unified medical language system; Semantic consistency ID MEDICAL LANGUAGE SYSTEM; METATHESAURUS AB Objectives: To quantify semantic inconsistency in UMLS concepts from the perspective of their hierarchical relations and to show through examples how semantically-inconsistent concepts can help reveal erroneous synonymy relations. Methods: Inconsistency is defined in reference to concepts from the UMLS Metathesaurus. Consistency is evaluated by comparing the semantic groups of the two concepts in each pair of hierarchically-related concepts. A limited number of inconsistent concepts was inspected manually. Results: 81,512 concepts are inconsistent due to the differences in semantic groups between a concept and its parent. Four examples of wrong synonymy are presented. Conclusions: A vast majority of inconsistent hierarchical relations are not indicative of any errors. We discovered an interesting semantic pattern along hierarchies, which seems associated with wrong synonymy. C1 [Erdogan, Halit; Erdem, Esra] Sabanci Univ, Fac Engn & Nat Sci, Istanbul, Turkey. [Bodenreider, Olivier] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Erdem, E (reprint author), Sabanci Univ, Fac Engn & Nat Sci, Istanbul, Turkey. EM esraerdem@sabanciuniv.edu; olivier@nlm.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); National Library of Medicine (NLM); TUBITAK [108E229] FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine (NLM), and TUBITAK Grant 108E229. NR 16 TC 2 Z9 2 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-588-4 J9 STUD HEALTH TECHNOL PY 2010 VL 160 BP 749 EP 753 DI 10.3233/978-1-60750-588-4-749 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BG8CS UT WOS:000392215900148 PM 20841786 ER PT S AU Wei, D Bodenreider, O AF Wei, Duo Bodenreider, Olivier BE Safran, C Reti, S Marin, HF TI Using the Abstraction Network in Complement to Description Logics for Quality Assurance in Biomedical Terminologies - A Case Study in SNOMED CT SO MEDINFO 2010, PTS I AND II SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 13th World Congress on Medical and Health Informatics of International-Medical-Informatics-Association (Medinfo) CY SEP 12-15, 2010 CL Cape Town, SOUTH AFRICA SP Int Med Informat Assoc DE Systematized nomenclature of medicine; Comparative study; Quality assurance; Description logics; Abstraction network AB Objectives: To investigate errors identified in SNOMED CT by human reviewers with help from the Abstraction Network methodology and examine why they had escaped detection by the Description Logic (DL) classifier. Case study; Two examples of errors are presented in detail (one missing IS-A relation and one duplicate concept). After correction, SNOMED CT is reclassified to ensure that no new inconsistency was introduced. Conclusions: DL-based auditing techniques built in terminology development environments ensure the logical consistency of the terminology. However, complementary approaches are needed for identifying and addressing other types of errors. C1 [Wei, Duo] New Jersey Inst Technol, Struct Anal Biomed Ontol Ctr, Newark, NJ 07102 USA. [Bodenreider, Olivier] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Wei, D (reprint author), New Jersey Inst Technol, Struct Anal Biomed Ontol Ctr, Newark, NJ 07102 USA. EM dw59@njit.edu; olivier@nlm.nih.gov FU Intramural Research Program of the National Institutes of Health (NIH); National Library of Medicine (NLM) [R-01-LM008912-01A1] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine (NLM). This work was done while Duo Wei was a visiting fellow at the Lister Hill National Center for Biomedical Communications, NLM, NIH. This work was also partially supported by the NLM under grant R-01-LM008912-01A1. NR 11 TC 8 Z9 8 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-588-4 J9 STUD HEALTH TECHNOL PY 2010 VL 160 BP 1070 EP 1074 DI 10.3233/978-1-60750-588-4-1070 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BG8CS UT WOS:000392215900210 PM 20841848 ER PT S AU Cimino, JJ Ayres, EJ AF Cimino, James J. Ayres, Elaine J. BE Safran, C Reti, S Marin, HF TI The Clinical Research Data Repository of the US National Institutes of Health SO MEDINFO 2010, PTS I AND II SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 13th World Congress on Medical and Health Informatics of International-Medical-Informatics-Association (Medinfo) CY SEP 12-15, 2010 CL Cape Town, SOUTH AFRICA SP Int Med Informat Assoc DE Clinical research; Data repositories; Controlled terminologies and ontologies; Data reuse AB The US National Institutes of Health (NIH) includes 27 institutes and centers, many of which conduct clinical research. Previously, data collected in research trials has existed in multiple, disparate databases. This paper describes the design, implementation and experience to date with the Biomedical Translational Research Information System (BTRIS), being developed at NIH to consolidate clinical research data. BTRIS is intended to simplify data access and analysis of data from active clinical trials and to facilitate reuse of existing data to answer new questions. Unique aspects of the system includes a Research Entities Dictionary that unifies all controlled terminologies used by source systems and a hybrid data model that unifies parts of the source data models and include other data in entity-attribute-value tables. BTRIS currently includes over 300 million rows of data, from three institutes, ranging from 1976 to present. Users are able to retrieve data on their own research subjects in identified form as well as deidentified data on all subjects. C1 [Cimino, James J.; Ayres, Elaine J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Cimino, JJ (reprint author), US Natl Inst Clin Ctr, Lab Informat Dev, 10 Ctr Dr,Room 6-2551, Bethesda, MD 20892 USA. EM James.Cimino@nih.gov OI Cimino, James/0000-0003-4101-1622 FU Intramural Research Program of the NIH FX This research was supported by the Intramural Research Program of the NIH. NR 9 TC 19 Z9 19 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-588-4 J9 STUD HEALTH TECHNOL PY 2010 VL 160 BP 1299 EP 1303 DI 10.3233/978-1-60750-588-4-1299 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BG8CS UT WOS:000392215900255 PM 20841894 ER PT S AU Bodenreider, O Burgun, A AF Bodenreider, Olivier Burgun, Anita BE Safran, C Reti, S Marin, HF TI A Framework for Comparing Phenotype Annotations of Orthologous Genes SO MEDINFO 2010, PTS I AND II SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 13th World Congress on Medical and Health Informatics of International-Medical-Informatics-Association (Medinfo) CY SEP 12-15, 2010 CL Cape Town, SOUTH AFRICA SP Int Med Informat Assoc DE Phenotype; Comparative study; Medical informatics computing; Medical subject headings ID MOUSE; GENOME; ASSOCIATION AB Objectives: Animal models are a key resource for the investigation of human diseases. In contrast to functional annotation, phenotype annotation is less standard, and comparing phenotypes across species remains challenging. The objective of this paper is to propose a framework for comparing phenotype annotations of orthologous genes based on the Medical Subject Headings (MeSH) indexing of biomedical articles in which these genes are discussed. Methods: 17,769 pairs of orthologous genes (mouse and human) are downloaded from the Mouse Genome Informatics (MGI) system and linked to biomedical articles through Entrez Gene. MeSH index terms corresponding to diseases are extracted from Medline. Results: 11,111 pairs of genes exhibited at least one phenotype annotation for each gene in the pair. Among these, 81% have at least one phenotype annotation in common, 80% have at least one annotation specific to the human gene and 84% have at least one annotation specific to the mouse gene. Four disease categories represent 54% of all phenotype annotations. Conclusions: This framework supports the curation of phenotype annotation and the generation of research hypotheses based on comparative studies. C1 [Bodenreider, Olivier] NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. [Burgun, Anita] Univ Rennes 1, Sch Med, Div INSERM U936, IFR 140, Rennes, France. RP Bodenreider, O (reprint author), NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM olivier@nlm.nih.gov; anita.burgun@univ-rennes1.fr FU Intramural Research Program of the National Institutes of Health (NIH); National Library of Medicine (NLM) FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine (NLM). Our thanks go to Ramez Ghazzaoui who helped set up Virtuoso. NR 13 TC 1 Z9 1 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-588-4 J9 STUD HEALTH TECHNOL PY 2010 VL 160 BP 1309 EP 1313 DI 10.3233/978-1-60750-588-4-1309 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BG8CS UT WOS:000392215900257 PM 20841896 ER PT S AU Nussenblatt, RB Bielekova, B Childs, R Krensky, A Strober, W Trinchieri, G AF Nussenblatt, Robert B. Bielekova, Bibiana Childs, Richard Krensky, Alan Strober, Warren Trinchieri, Giorgio BA Nussenblatt, RB Bielekova, B Childs, R Krensky, A Strober, W Trinchieri, G BF Nussenblatt, RB Bielekova, B Childs, R Krensky, A Strober, W Trinchieri, G CA Ctr Human Immunology Autoimmunity Natl Inst Hlth TI Meeting the human immunology challenge National Institutes of Health Center for Human Immunology Conference, September 2009 SO MEETING THE HUMAN IMMUNOLOGY CHALLENGE SE Annals of the New York Academy of Sciences LA English DT Article DE immunology; bench-to-bedside approaches; immunobiology ID REGULATORY T-CELLS; MULTIPLE-SCLEROSIS; CLINICAL-TRIAL; MACULAR DEGENERATION; MONOCLONAL-ANTIBODY; CANCER REGRESSION; INTERFERON-BETA; ALPHA-CHAIN; RECEPTOR; THERAPY AB Although studies of the laboratory mouse model have laid the groundwork for our rich understanding of immunobiology, they have fallen short in deciphering human disease and providing much needed therapeutic modalities. Indeed, bench-to-bedside approaches have not been a particularly effective means of developing translational research. 1 Recently, a symposium was held at the National Institutes of Health (NIH) entitled "Meeting the Human Immunology Challenge," highlighting the opportunities for the new Intramural NIH Center for Human Immunology, Autoimmunity, and Inflammation (http://www.nhlbi.nih.gov/resources/chi/); among other things it has become clear that a broader definition of the human immune spectrum in health and disease is needed. The human immunology meeting was held in the Clinical Center of the National Institutes of Health, Bethesda, Maryland, on September 3 and 4, 2009. C1 [Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Bielekova, Bibiana] NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Childs, Richard] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Krensky, Alan] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Strober, Warren] NIAID, Mucosal Immun Sect, Bethesda, MD 20892 USA. [Trinchieri, Giorgio] NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov RI Krensky, Alan/F-7956-2011; Saude Publica, Inct/J-9544-2013; Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 NR 65 TC 11 Z9 11 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-798-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1200 IS S1 BP E1 EP E23 DI 10.1111/j.1749-6632.2010.05682.x PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BTW49 UT WOS:000288271500001 PM 20633145 ER PT S AU Ferre, S Navarro, G Casado, V Cortes, A Mallol, J Canela, EI Lluis, C Franco, R AF Ferre, Sergi Navarro, Gemma Casado, Vicent Cortes, Antoni Mallol, Josefa Canela, Enric I. Lluis, Carme Franco, Rafael BE Lunn, CA TI G Protein-Coupled Receptor Heteromers as New Targets for Drug Development SO MEMBRANE PROTEINS AS DRUG TARGETS SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID RESONANCE ENERGY-TRANSFER; DELTA-OPIOID RECEPTORS; HIGHER-ORDER OLIGOMERS; ADENOSINE A(2A); LIVING CELLS; HETERODIMERIZATION; DOPAMINE-D-2; PHARMACOLOGY; DISTINCT; LIGAND C1 [Ferre, Sergi] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD USA. [Navarro, Gemma; Casado, Vicent; Cortes, Antoni; Mallol, Josefa; Canela, Enric I.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, CIBERNED, Barcelona, Spain. [Franco, Rafael] CIMA Neurociencias, Pamplona, Spain. RP Ferre, S (reprint author), Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD USA. RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014 OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; FU Intramural NIH HHS NR 55 TC 29 Z9 29 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-381288-9 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2010 VL 91 BP 41 EP 52 DI 10.1016/S1877-1173(10)91002-8 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQT15 UT WOS:000281774300002 PM 20691958 ER PT S AU Calcagno, AM Ambudkar, SV AF Calcagno, Anna Maria Ambudkar, Suresh V. BA Yan, Q BF Yan, Q TI Analysis of Expression of Drug Resistance-Linked ABC Transporters in Cancer Cells by Quantitative RT-PCR SO MEMBRANE TRANSPORTERS IN DRUG DISCOVERY AND DEVELOPMENT: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Quantitative real-time PCR (qRT-PCR); SYBR green; TaqMan; ABC transporters; gene expression profiling ID MULTIDRUG-RESISTANCE; GENE-EXPRESSION; CHEMOSENSITIVITY; PROTEINS; LINES AB Quantitative real-time PCR (qRT-PCR) boasts many advantages over microarrays. For instance, very low amounts of total RNA are required to yield highly accurate and reproducible detection of transcript levels. As a consequence, qRT-PCR has become a popular technique for assessing gene expression levels and is now the gold standard. In this chapter, qRT-PCR using two distinct chemistries, SYBR Green and TaqMan, are described. We compare ABC transporter levels in various drug-resistant cancer cell lines by employing each method. SYBR Green yields reproducible results; nevertheless, TaqMan chemistry is superior to SYBR Green, as it displays higher specificity and sensitivity. Gene expression analysis by qRT-PCR is a powerfitl technique and shows potential as a diagnostic tool for predicting drug response in cancer patients. C1 [Calcagno, Anna Maria; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Calcagno, AM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RI Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU Intramural NIH HHS [Z01 BC010030-12] NR 20 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-699-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 637 BP 121 EP 132 DI 10.1007/978-1-60761-700-6_6 D2 10.1007/978-1-60761-700-6 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOU19 UT WOS:000277617000006 PM 20419432 ER PT J AU Sutin, AR Robins, RW AF Sutin, Angelina R. Robins, Richard W. TI Correlates and phenomenology of first and third person memories SO MEMORY LA English DT Article DE Visual perspective; Autobiographical memory; Personality; Phenomenology; Dissociation ID RECALL VANTAGE PERSPECTIVE; AUTOBIOGRAPHICAL MEMORY; SOCIAL PHOBIA; AUTONOETIC CONSCIOUSNESS; VISUAL PERSPECTIVE; INTRUSIVE MEMORIES; SELF-PERSPECTIVE; EPISODIC MEMORY; TRAUMA MEMORIES; POINT AB The present research addressed fundamental questions about the visual perspective of autobiographical memories: Are stable personality characteristics associated with visual perspective? Does visual perspective influence the memory's phenomenological qualities? Participants in Study 1 (N=1684) completed individual-difference measures and indicated the perspective from which they generally retrieve memories. Participants in Study 2 (N=706) retrieved a memory from their natural or manipulated perspective, rated its phenomenology, and completed the same individual-difference measures. Dissociation and anxiety were associated with third person retrieval style; the Big Five personality traits were primarily unrelated to perspective. Compared to third person memories, naturally occurring first person memories were higher on Vividness, Coherence, Accessibility, Sensory Detail, Emotional Intensity, and Time Perspective, and lower on Distancing; manipulating perspective eliminated these differences. Visual perspective is associated with clinically relevant constructs and, although associated with the memory's phenomenology, perspective does not shape it. C1 [Sutin, Angelina R.] NIA, NIH Biomed Res Ctr, IRP, Baltimore, MD 21224 USA. [Robins, Richard W.] Univ Calif Davis, Davis, CA 95616 USA. RP Sutin, AR (reprint author), NIA, NIH Biomed Res Ctr, IRP, 251 Bayview Blvd,Suite 100,Room 04B323, Baltimore, MD 21224 USA. EM sutina@mail.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 47 TC 14 Z9 14 U1 3 U2 22 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0965-8211 J9 MEMORY JI Memory PY 2010 VL 18 IS 6 BP 625 EP 637 AR PII 924776781 DI 10.1080/09658211.2010.497765 PG 13 WC Psychology, Experimental SC Psychology GA 637KL UT WOS:000280816100005 PM 20665336 ER PT S AU Vaccari, M Franchini, G AF Vaccari, Monica Franchini, Genoveffa BE Zanetti, M Schoenberger, SP TI Memory T Cells in Rhesus Macaques SO MEMORY T CELLS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID SIMIAN-IMMUNODEFICIENCY-VIRUS; IMMUNOLOGICAL SELF-TOLERANCE; VIRAL SET-POINT; IN-VIVO; NONHUMAN-PRIMATES; HIV-1 INFECTION; GASTROINTESTINAL-TRACT; FLOW-CYTOMETRY; SIV INFECTION; HOMEOSTATIC PROLIFERATION AB The Rhesus macaque (Maraca mulatta) is one of the best studied species of Old World monkeys. DNA sequencing of the entire Rhesus macaque genome, completed in 2007, has demonstrated that humans and macaques share about 93% of their nucleotide sequence. Rhesus macaques have been widely used for medical research including drug testing, neurology, behavioral and cognitive science, reproduction, xenotransplantation and genetics. Because of the Rhesus macaque's sensitivity to bacteria, parasites and viruses that cause similar disease in humans, these animals represent an excellent model to study infectious diseases. The recent pandemic of HIV and the discovery of SIV, a lentivirus genetically related to HIV Type 1 that causes AIDS in Rhesus macaques, have prompted the development of reagents that can be used to study innate and adaptive immune responses in macaques at the single cell level. This review will focus on the distribution of memory cells in the different immunologic compartments of Rhesus macaques. In addition, the strategies available to manipulate memory cells in Rhesus macaques to understand their trafficking and function will be discussed. Emphasis is placed on studies of memory cells in macaques infected with Sly because many studies are available. Lastly, we highlight the usefulness of the Rhesus macaque model in studies related to the aging of the immune system. C1 [Franchini, Genoveffa] NCI, Anim Models & Retrovira Vaccine Sect, NIH, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retrovira Vaccine Sect, NIH, Bldg 41,Room D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov NR 167 TC 6 Z9 6 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-6450-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 684 BP 126 EP 144 D2 10.1007/978-1-4419-6451-9 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BPI50 UT WOS:000278923300010 PM 20795545 ER PT S AU Slezak, SL Worschech, A Wang, E Stroncek, DF Marincola, FM AF Slezak, Stefanie L. Worschech, Andrea Wang, Ena Stroncek, David F. Marincola, Francesco M. BE Zanetti, M Schoenberger, SP TI Analysis of Vaccine-Induced T Cells in Humans with Cancer SO MEMORY T CELLS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID MELANOMA PATIENTS; SPONTANEOUS REGRESSION; METASTATIC MELANOMA; GENE-EXPRESSION; SOLID TUMORS; PULMONARY METASTASES; PERIPHERAL-BLOOD; FLOW-CYTOMETRY; IMMUNOTHERAPY; IMMUNIZATION AB Over the past several years, progress in the field of tumor immunology has lead to advances in active immunotherapy and vaccination as a means of eliciting tumor-specific immune responses to mediate tumor regression and clearance. Developing vaccines targeted against cancer became an important focus as a therapy following the success of viral vaccines in preventing infection and disease. In humans with cancer, similar to viral infections, the host immune system is capable of recognizing antigens expressed on tumor cells. This similarity allows the immunological framework of the viral vaccine to be adapted to the cancer setting in hopes of enhancing human T-cell reactivity against tumor.(1) It is generally believed that a requirement for tumor destruction to occur is the induction of sufficient levels of immune cells with high avidity for recognition of tumor antigens. Moreover, the cells must be targeted to the tumor site and be capable of infiltrating tumor stroma.(2) Several tumor-associated antigens (TAA) have been identified in the melanoma model which has allowed for immunization trials to evaluate therapeutic potential of tumor-specific T-cell induction. Some clinical trials reported limited success of T-cell mediated tumor rejection, reporting partial or complete regression in 10 to 30% of patients.(3) Although tumor regression was not observed following active immunization in vivo, ex vivo assays evaluating TAA-specific T cells demonstrated tumor recognition and subsequent T-cell activation suggesting that tumor-specific T-cell induction indeed occurs but alone is not adequate to induce tumor regression.(1) Recently, the usefulness and success of active-specific immunization (ASI) against TAAs as a means of eliciting a tumor-specific immune response leading to tumor regression and clearance has been a topic of debate and discussion. C1 [Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fmarincola@mail.cc.nih.gov RI Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 NR 64 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-6450-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 684 BP 178 EP 188 D2 10.1007/978-1-4419-6451-9 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BPI50 UT WOS:000278923300014 PM 20795549 ER PT J AU Martiniova, L Schimel, D Lai, EW Limpuangthip, A Kvetnansky, R Pacak, K AF Martiniova, Lucia Schimel, Daniel Lai, Edwin W. Limpuangthip, Andrea Kvetnansky, Richard Pacak, Karel TI In vivo micro-CT imaging of liver lesions in small animal models SO METHODS LA English DT Review DE Pheochromocytoma; Anatomical imaging; MicroCT; Liver lesions; Fusion ID SELECTIVE CONTRAST AGENT; COMPUTED-TOMOGRAPHY; METASTATIC PHEOCHROMOCYTOMA; ENHANCEMENT; TUMORS; TRIGLYCERIDE; DISEASE; TIME AB Three-dimensional micro computed tomography (microCT) offers the opportunity to capture images liver structures and lesions in mice with a high spatial resolution. Non-invasive microCT allows for accurate calculation of vessel tortuosity and density, as well as liver lesion volume and distribution. Longitudinal monitoring of liver lesions is also possible. However, distinguishing liver lesions from variations within a normal liver is impossible by microCT without the use of liver- or tumor-specific contrast-enhancing agents. The combination of microCT for morphologic imaging with functional imaging, such as positron emission tomography (PET) or single photon emission tomography (SPECT), offers the opportunity for better abdominal imaging and assessment of structure discrepancies visible by functional imaging. This paper describes methods of current microCT imaging options for imaging of liver lesions compared to other imaging techniques in small animals. Published by Elsevier Inc. C1 [Martiniova, Lucia; Lai, Edwin W.; Limpuangthip, Andrea; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA. [Schimel, Daniel] Natl Inst Neurol Disorders & Stroke, Mouse Imaging Facil, Charles River Labs, Bethesda, MD 20892 USA. [Martiniova, Lucia; Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. RP Pacak, K (reprint author), NICHD, NIH, Bldg 10,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU NIH/NICHD [APVV-0148-06] FX We thank the contributions and assistance of Dr. Arthur S. Tischler for his help and guidance. We thank Dr. Brenda Klaunberg and the intramural shared resources for microCT imaging in the Mouse Imaging Facility. We thank Eli Thompson for his assistance with the animals and Mrs. Evin O'Keeffe for her help with editing. This research was supported (in part) by the Intramural Research Program of the NIH/NICHD and APVV-0148-06 (to RX). The authors have no conflict of interest to disclose. NR 29 TC 25 Z9 26 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JAN PY 2010 VL 50 IS 1 BP 20 EP 25 DI 10.1016/j.ymeth.2009.05.016 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 544GG UT WOS:000273641400004 PM 19520168 ER PT S AU Song, BJ Suh, SK Moon, KH AF Song, Byoung-Joon Suh, Soo-Kyung Moon, Kwan-Hoon BE Cadenas, E Packer, L TI A SIMPLE METHOD TO SYSTEMATICALLY STUDY OXIDATIVELY MODIFIED PROTEINS IN BIOLOGICAL SAMPLES AND ITS APPLICATIONS SO METHODS IN ENZYMOLOGY, VOL 473: THIOL REDOX TRANSITIONS IN CELL SIGNALING, PT A: CHEMISTRY AND BIOCHEMISTRY OF LOW MOLECULAR WEIGHT AND PROTEIN THIOLS SE Methods in Enzymology LA English DT Review; Book Chapter ID ALCOHOLIC FATTY LIVER; MITOCHONDRIAL ALDEHYDE DEHYDROGENASE; NITRIC-OXIDE; S-NITROSYLATION; RAT-LIVER; REACTIVE OXYGEN; HEPATOMA-CELLS; MOUSE-LIVER; INACTIVATION; DYSFUNCTION AB Increased oxidative stress with elevated levels of reactive oxygen/nitrogen species (ROS/RNS) plays an important role in the pathophysiology of many disease states. Increased ROS/RNS can modulate the cellular macromolecules of DNA, lipids, and proteins, negatively affecting their normal functions. Numerous reports have described the properties and implications of oxidized DNA and lipids. However, oxidative modifications of proteins were not fully studied partially due to the requirement for specific reagents, the lack of methods to detect, purify, and identify oxidatively modified proteins, and the relatively late development of highly sensitive analytical instruments. This chapter describes the detailed procedure for systematically identifying oxidative-modified proteins in biological samples. Applications and other suggestions to this method are also described to understand the functional roles of oxidatively modified proteins in promoting endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which ultimately contribute to organ damage. C1 [Song, Byoung-Joon; Suh, Soo-Kyung; Moon, Kwan-Hoon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 90034 USA. [Suh, Soo-Kyung] Korea Food & Drug Adm, Natl Inst Food & Drug Evaluat, Natl Ctr Toxicol Res, Seoul, South Korea. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 90034 USA. FU Intramural NIH HHS [ZIA AA000036-23, Z99 AA999999] NR 41 TC 10 Z9 11 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-381345-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 473 BP 251 EP 264 DI 10.1016/S0076-6879(10)73013-5 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BPK52 UT WOS:000279058700013 PM 20513482 ER PT S AU Turanov, AA Hatfield, DL Gladyshev, VN AF Turanov, Anton A. Hatfield, Dolph L. Gladyshev, Vadim N. BE Cadenas, E Packer, L TI CHARACTERIZATION OF PROTEIN TARGETS OF MAMMALIAN THIOREDOXIN REDUCTASES SO METHODS IN ENZYMOLOGY, VOL 474: THIOL REDOX TRANSITIONS IN CELL SIGNALING, PT B: CELLULAR LOCALIZATION AND SIGNALING SE Methods in Enzymology LA English DT Review; Book Chapter ID SELENOCYSTEINE; MECHANISM; SELENOPROTEINS; CLONING AB Mammalian thioredoxin reductases (TRs) are members of the pyridine nucleotide-disulfide oxidoreductase family. The main function of these enzymes is to maintain thioredoxins (Trxs) in the reduced state. The accessibility and high reactivity of selenocysteine in the C-terminal tetrapeptide allows mammalian TRs to couple to a range of substrates from proteins, such as Trx, to small molecules, such as selenite and hydroperoxides. However, identification of physiological substrates of TRs remains a challenge, with new targets identified primarily by testing random candidates in in vitro assays. The reaction mechanism of TRs supports a procedure that could trap substrates in a covalent nonproductive complex with TRs. Accordingly, attachment of TRs to affinity matrices allows isolation and identification of these targets. Application of this method revealed that Trxs are the major targets of TRs and supported efficient isolation of Trx substrates on TR affinity columns. We suggest that this procedure may be used as a general method of affinity isolation of Trxs and other TR substrates. C1 [Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Turanov, Anton A.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Turanov, AA (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS; NIA NIH HHS [R01 AG021518, R01 AG021518-08]; NIGMS NIH HHS [R01 GM061603] NR 19 TC 4 Z9 4 U1 2 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-381003-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 474 BP 245 EP 254 DI 10.1016/S0076-6879(10)74014-3 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BPV82 UT WOS:000280112000014 PM 20609914 ER PT S AU Yoo, MH Carlson, BA Tsuji, P Irons, R Gladyshev, VN Hatfield, DL AF Yoo, Min-Hyuk Carlson, Bradley A. Tsuji, Petra Irons, Robert Gladyshev, Vadim N. Hatfield, Dolph L. BE Cadenas, E Packer, L TI ALTERATION OF THIOREDOXIN REDUCTASE 1 LEVELS IN ELUCIDATING CANCER ETIOLOGY SO METHODS IN ENZYMOLOGY, VOL 474: THIOL REDOX TRANSITIONS IN CELL SIGNALING, PT B: CELLULAR LOCALIZATION AND SIGNALING SE Methods in Enzymology LA English DT Review; Book Chapter ID SELENIUM; SELENOCYSTEINE; CELLS; SELENOPROTEINS; PREVENTION; EXPRESSION; RESIDUE; THIOREDOXIN-REDUCTASE-1; TRANSCRIPTION; PHENOTYPE AB Thioredoxin reductase 1 (TR1) is a major antioxidant and redox regulator in mammalian cells and appears to function as a double-edged sword in that it has roles in preventing and promoting/sustaining cancer. TR1 is overexpressed in many cancer cells and targeting its removal often leads to a reversal in numerous malignant characteristics which has marked this selenoenzyme as a prime target for cancer therapy. Since alterations in TR1 activity may lead to a better understanding of the etiology of cancer and new avenues for providing better therapeutic procedures, we have described herein techniques for removing and reexpressing TR1 employing RNAi technology and for assessing the catalytic activity of this enzyme. C1 [Yoo, Min-Hyuk; Carlson, Bradley A.; Tsuji, Petra; Irons, Robert; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Tsuji, Petra] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. [Tsuji, Petra] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. RP Yoo, MH (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS; NCI NIH HHS [R01 CA080946-11, R01 CA080946]; NIGMS NIH HHS [R01 GM065204, R01 GM065204-09, R01 GM061603] NR 49 TC 8 Z9 8 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 0076-6879 BN 978-0-12-381003-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 474 BP 255 EP 275 DI 10.1016/S0076-6879(10)74015-5 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BPV82 UT WOS:000280112000015 PM 20609915 ER PT S AU Manley, S Gillette, JM Lippincott-Schwartz, J AF Manley, Suliana Gillette, Jennifer M. Lippincott-Schwartz, Jennifer BE Walter, NG TI SINGLE-PARTICLE TRACKING PHOTOACTIVATED LOCALIZATION MICROSCOPY FOR MAPPING SINGLE-MOLECULE DYNAMICS SO METHODS IN ENZYMOLOGY, VOL 475: SINGLE MOLECULE TOOLS, PT B: SUPER-RESOLUTION, PARTICLE TRACKING, MULTIPARAMETER, AND FORCE BASED METHODS SE Methods in Enzymology LA English DT Review; Book Chapter ID LOW-DENSITY-LIPOPROTEIN; FLUORESCENT PROTEIN; CELL-SURFACE; LIVING CELLS; IN-VIVO; PROBES; TAG; GFP AB Recent developments in single-molecule localization techniques using photoactivatable fluorescent proteins have allowed the probing of single-molecule motion in a living cell with high specificity, millisecond time resolution, and nanometer spatial resolution. Analyzing the dynamics of individual molecules at high densities in this manner promises to provide new insights into the mechanisms of many biological processes, including protein heterogeneity in the plasma membrane, the dynamics of cytoskeletal flow, and clustering of receptor complexes in response to signaling cues. Here we describe the method of single-molecule tracking photoactivated localization microscopy (sptPALM) and discuss how its use can contribute to a quantitative understanding of fundamental cellular processes. C1 [Manley, Suliana] Swiss Fed Inst Technol EPFL, Inst Phys Biol Syst, Lausanne, Switzerland. [Gillette, Jennifer M.; Lippincott-Schwartz, Jennifer] NICHD, Sect Organelle Biol, Cell Biol & Metab Program, NIH, Bethesda, MD USA. RP Manley, S (reprint author), Swiss Fed Inst Technol EPFL, Inst Phys Biol Syst, Lausanne, Switzerland. RI Manley, Suliana/D-3818-2012 OI Manley, Suliana/0000-0002-4755-4778 FU Intramural NIH HHS [ZIA HD001609-19] NR 34 TC 30 Z9 30 U1 0 U2 17 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-381482-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 475 BP 109 EP 120 DI 10.1016/S0076-6879(10)75005-9 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQD36 UT WOS:000280733800005 PM 20627155 ER PT S AU Sharov, AA Piao, Y Ko, MSH AF Sharov, Alexei A. Piao, Yulan Ko, Minoru S. H. BE Wassarman, PM Soriano, PM TI GENE EXPRESSION PROFILING OF MOUSE EMBRYOS WITH MICROARRAYS SO METHODS IN ENZYMOLOGY, VOL 477: GUIDE TO TECHNIQUES IN MOUSE DEVELOPMENT, PART B: MOUSE MOLECULAR GENETICS, SECOND EDITION SE Methods in Enzymology LA English DT Review; Book Chapter ID GENOME-WIDE; STEM-CELLS; RNA-SEQ; OLIGONUCLEOTIDE MICROARRAY; TRANSCRIPTION; BIOLOGY; TOOL; PLURIPOTENT; PATTERNS; ACID AB Global expression profiling by DNA microarrays provides a snapshot of cell and tissue status and becomes an essential tool in biological and medical sciences. Typical questions that can be addressed by microarray analysis in developmental biology include: (1) to find a set of genes expressed in a specific cell type; (2) to identify genes expressed commonly in multiple cell types; (3) to follow the time-course changes of gene expression patterns; (4) to demonstrate cell's identity by showing similarities or differences among two or multiple cell types; (5) to find regulatory pathways and/or networks affected by gene manipulations, such as overexpression or repression of gene expression; (6) to find downstream target genes of transcription factors; (7) to find downstream target genes of cell signaling; (8) to examine the effects of environmental manipulation of cells on gene expression patterns; and (9) to find the effects of genetic manipulation in embryos and adults. Here, we describe strategies for executing these experiments and monitoring changes of cell state with gene expression microarrays in application to mouse embryology. Both statistical assessment and interpretation of data are discussed. We also present a protocol for performing microarray analysis on a small amount of embryonic materials. C1 [Sharov, Alexei A.; Piao, Yulan; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Sharov, AA (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS [ZIA AG000700-03, ZIA AG000655-12, ZIA AG000656-12, ZIA AG000662-10, ZIA AG000678-03, ZIA AG000702-03] NR 79 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-384882-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 477 BP 511 EP 541 DI 10.1016/S0076-6879(10)77025-7 PG 31 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQT19 UT WOS:000281776700025 PM 20699157 ER PT S AU Wilson-Kubalek, EM Chappie, JS Arthur, CP AF Wilson-Kubalek, Elizabeth M. Chappie, Joshua S. Arthur, Christopher P. BE Jensen, GJ TI HELICAL CRYSTALLIZATION OF SOLUBLE AND MEMBRANE BINDING PROTEINS SO METHODS IN ENZYMOLOGY, VOL 481: CRYO-EM, PART A - SAMPLE PREPARATION AND DATA COLLECTION SE Methods in Enzymology LA English DT Review; Book Chapter ID BOTULINUM NEUROTOXIN-B; NICOTINIC ACETYLCHOLINE-RECEPTOR; DEPENDENT CONFORMATIONAL-CHANGES; CLATHRIN-MEDIATED ENDOCYTOSIS; FUNCTIONALIZED LIPID TUBULES; GTPASE DOMAIN MUTANTS; COLI RNA-POLYMERASE; BAR DOMAINS; PHOSPHOINOSITIDE-BINDING; ELECTRON CRYOMICROSCOPY AB Helical protein arrays offer unique advantages for structure determination by cryo-electron microscopy (cryo-EM). A single image of such an array contains a complete range of equally spaced molecular views of the underlying protein subunits, which allows a low-resolution, isotropic three-dimensional (3D) map to be generated from a single helical tube without tilting the sample in the electron beam as is required for two-dimensional (2D) crystals. Averaging many unit cells from a number of similar tubes can improve the signal-to-noise ratio and consequently, the quality of the 3D map. This approach has yielded reconstructions that approach atomic resolution [Miyazawa et al., 1999, 2003; Sachse et al., 2007; Unwin, 2005; Yonekura et al., 2005]. Proteins that naturally adopt helical protein arrays, such as actin and microtubules, have been studied for decades. The wealth of information on how proteins bind and move along these cytoskeletal tracks, provide cross-talk between tracks, and integrate into the cellular machinery is due, in part, to multiple EM studies of the helical assemblies. Since the majority of proteins do not spontaneously form helical arrays, the power of helical image analysis has only been realized for a small number of proteins. This chapter describes the use of functionalized lipid nanotubes and liposomes as substrates to bind and form helical arrays of soluble and membrane-associated proteins. C1 [Wilson-Kubalek, Elizabeth M.; Arthur, Christopher P.] Scripps Res Inst, La Jolla, CA 92037 USA. [Chappie, Joshua S.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wilson-Kubalek, EM (reprint author), Scripps Res Inst, La Jolla, CA 92037 USA. FU NIGMS NIH HHS [GM52468, GM61941, GM61938, GM75820] NR 69 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374906-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 481 BP 45 EP 62 DI 10.1016/S0076-6879(10)81002-X PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BRR95 UT WOS:000283516900003 PM 20887852 ER PT S AU Bilsky, EJ Giuvelis, D Osborn, MD Dersch, CM Xu, H Rothman, RB AF Bilsky, Edward J. Giuvelis, Denise Osborn, Melissa D. Dersch, Christina M. Xu, Heng Rothman, Richard B. BE Conn, PM TI IN VITRO AND IN VIVO ASSESSMENT OF MU OPIOID RECEPTOR CONSTITUTIVE ACTIVITY SO METHODS IN ENZYMOLOGY, VOLUME 484: CONSTITUTIVE ACTIVITY IN RECEPTORS AND OTHER PROTEINS, PART A SE Methods in Enzymology LA English DT Review; Book Chapter ID APPARENT PA(2) ANALYSIS; PRECIPITATED WITHDRAWAL; NEUTRAL ANTAGONISTS; NARCOTIC DEPENDENCE; PHYSICAL-DEPENDENCE; INVERSE AGONISTS; G-PROTEINS; MORPHINE; TOLERANCE; ACTIVATION AB Constitutive (basal) signaling has been described and characterized for numerous G protein coupled receptors (GPCRs). The relevance of this activity to disease, drug discovery and development, and to clinical pharmacotherapy is just beginning to emerge. Opioid receptors were the first GPCR systems for which there was definitive evidence presented for constitutive activity, with numerous studies now published on the regulation of this activity (e.g., structure/activity of the receptor as it relates to basal activity, pharmacology of ligands that act as agonists, inverse agonists and "neutral antagonists," etc.). This chapter summarizes some of the methods used to characterize constitutive activity at the mu opioid receptor (MOR) in preclinical in vitro and in vivo model systems. This includes cell-based systems that are useful for higher throughput screening of novel ligands and for studying variables that can impact basal tone in a system. In vivo assays are also described in which constitutive activity is increased in response to acute or chronic opioid agonist exposure and where withdrawal is precipitated with antagonists that may function as inverse agonists or "neutral" antagonists. The methods described have inherent advantages and disadvantages that need to be considered in any drug discovery/development program. A brief discussion of progress toward understanding the clinical implications of MOR constitutive activity in the management of opioid addiction and chronic pain is also included in this chapter. C1 [Bilsky, Edward J.; Giuvelis, Denise; Osborn, Melissa D.] Univ New England, Dept Biomed Sci, Coll Osteopath Med, Biddeford, ME USA. [Dersch, Christina M.; Xu, Heng; Rothman, Richard B.] IRP NIDA NIH, Clin Psychopharmacol Sect, Baltimore, MD USA. RP Bilsky, EJ (reprint author), Univ New England, Dept Biomed Sci, Coll Osteopath Med, Biddeford, ME USA. FU Intramural NIH HHS NR 38 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-381298-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 484 BP 413 EP 443 DI 10.1016/S0076-6879(10)84021-2 PG 31 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSI07 UT WOS:000284508500021 PM 21036244 ER PT S AU Neumann, S Raaka, BM Gershengorn, MC AF Neumann, Susanne Raaka, Bruce M. Gershengorn, Marvin C. BE Conn, PM TI CONSTITUTIVELY ACTIVE THYROTROPIN AND THYROTROPIN-RELEASING HORMONE RECEPTORS AND THEIR INVERSE AGONISTS SO METHODS IN ENZYMOLOGY, VOLUME 485: CONSTITUTIVE ACTIVITY IN RECEPTORS AND OTHER PROTEINS, PART B SE Methods in Enzymology LA English DT Review; Book Chapter ID ANTIBODY; TRH AB Receptors for thyrotropin-releasing hormone (TRH) and thyrotropin (thyroid-stimulating hormone-TSH) are important regulators of the function of the TSH-producing cells of the anterior pituitary gland and the thyroid gland, respectively, and thereby play a central role in thyroid hormone homeostasis. Although the roles of TRH- and TSH-stimulated signaling in these endocrine glands are well understood, these receptors are expressed in other sites and their roles in these extraglandular tissues are less well known. Moreover, one of the two subtypes of TRH- receptors (TRH-R2) and the single TSH receptor (TSHR) exhibit constitutive signaling activity and the roles of constitutive signaling by these receptors are poorly understood. One approach to studying constitutive signaling is to use inverse agonists. In this chapter, we will describe the experimental procedures used to measure constitutive signaling by TRH-R2 and TSHR and the effects of their specific inverse agonists. C1 [Neumann, Susanne; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Neumann, S (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 14 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-381296-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 485 BP 147 EP 160 DI 10.1016/S0076-6879(10)85009-8 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSI08 UT WOS:000284508700009 PM 21050916 ER PT S AU Schneider, EH Seifert, R AF Schneider, Erich H. Seifert, Roland BE Conn, PM TI FUSION PROTEINS AS MODEL SYSTEMS FOR THE ANALYSIS OF CONSTITUTIVE GPCR ACTIVITY SO METHODS IN ENZYMOLOGY, VOLUME 485: CONSTITUTIVE ACTIVITY IN RECEPTORS AND OTHER PROTEINS, PART B SE Methods in Enzymology LA English DT Review; Book Chapter ID SF9 INSECT CELLS; SPLICE VARIANTS; QUANTITATIVE-ANALYSIS; MOLECULAR ANALYSIS; GTPASE ACTIVITY; RGS PROTEINS; RECEPTOR; ACTIVATION; BETA(2)-ADRENOCEPTOR; ALPHA AB In many cases, the coexpression of GPCRs with G-proteins and/or regulators of G-protein signaling (RGS-proteins) allows a successful reconstitution of high-affinity agonist binding and functional responses. However, in some cases, coexpressed GPCRs and G-proteins interact inefficiently, resulting in weak [(35)S]GTP gamma S- and steady-state GTPase assay signals. This may be, for example, caused by a rapid dissociation of the G-protein from the plasma membrane, as has been reported for Gas. Moreover, for a detailed characterization of GPCR/G-protein interactions, it may be required to work with a defined GPCR/G-protein stoichiometry and to avoid cross-interaction with endogenous G-proteins. Cross-talk to endogenous G-proteins has been shown to play a role in some mammalian expression systems. These problems can be addressed by the generation of GPCR-G alpha fusion proteins and their expression in Sf9 insect cells. When the C-terminus of the receptor is fused to the N-terminus of the G-protein, a 1:1 stoichiometry of both proteins is achieved. In addition, the close proximity of GPCR and G-protein in fusion proteins leads to enhanced interaction efficiency, resulting in increased functional signals. This approach can also be extended to fusion proteins of GPCRs with RGS-proteins, specifically when steady-state GTP hydrolysis is used as read-out. GPCR-RGS fusion proteins optimize the interaction of RGS-proteins with coexpressed G alpha subunits, since the location of the RGS-protein is close to the site of receptor-mediated G-protein activation. Moreover, in contrast to coexpression systems, GPCR-G alpha and GPCR-RGS fusion proteins provide a possibility to imitate physiologically occurring interactions, for example, the precoupling of receptors and G-proteins or the formation of complexes between GPCRs, G-proteins and RGS-proteins (transducisomes). In this chapter, we describe the technique for the generation of fusion proteins and show the application of this approach for the characterization of constitutively active receptors. C1 [Schneider, Erich H.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Seifert, Roland] Hannover Med Sch, Inst Pharmacol, D-3000 Hannover, Germany. RP Schneider, EH (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Schneider, Erich/B-9051-2016 OI Schneider, Erich/0000-0002-7905-4276 NR 34 TC 6 Z9 6 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 0076-6879 BN 978-0-12-381296-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 485 BP 459 EP 480 DI 10.1016/S0076-6879(10)85025-6 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSI08 UT WOS:000284508700025 PM 21050932 ER PT S AU Schneider, EH Seifert, R AF Schneider, Erich H. Seifert, Roland BE Conn, PM TI COEXPRESSION SYSTEMS AS MODELS FOR THE ANALYSIS OF CONSTITUTIVE GPCR ACTIVITY SO METHODS IN ENZYMOLOGY, VOLUME 485: CONSTITUTIVE ACTIVITY IN RECEPTORS AND OTHER PROTEINS, PART B SE Methods in Enzymology LA English DT Review; Book Chapter ID FORMYL PEPTIDE RECEPTOR; HISTAMINE H-4 RECEPTOR; SF9 INSECT CELLS; G-PROTEIN; FUNCTIONAL RECONSTITUTION; INVERSE AGONISM; ACTIVATION; LIGANDS; H-2-RECEPTOR; H-4-RECEPTOR AB The investigation of constitutive activity of GPCRs in transfected mammalian cells is often hampered by the presence of other constitutively active receptors that generate a high background signal. This impairs the measurement of constitutive activity and of inverse agonistic effects, both of which often occur in a relatively small signal range. Moreover, constitutive activity of a GPCR depends on the interacting G-protein. Since the commonly used mammalian cells contain a set of several different G-protein types, it is very difficult to investigate the influence of specific G alpha and G beta gamma subunits on constitutive activity in more detail in these expression systems. Here, we show that the Sf9 cell/baculovirus expression system provides excellent conditions for the characterization of constitutively active GPCRs. Sf9 cells express a restricted set of G-protein subtypes that show only a limited capability of interacting with mammalian GPCRs. Moreover, the Sf9 cell/baculovirus expression system allows the combined expression of up to four different proteins encoded by the respective genetically modified baculoviruses. Using the highly constitutively active human histamine H(4)R (hH(4)R) as a paradigm, we demonstrate how the coexpression of hH(4)R with different signaling proteins (G alpha, G beta gamma, and RGS-proteins) in combination with sensitive functional assays (high-affinity agonist binding and steady-state GTPase- and GTP gamma S-binding assays) allows in-depth studies of constitutive activity. The preparation of Sf9 cell membranes, coexpressing hH(4)R and various additional proteins, is described in detail as well as the procedures of the different functional assays. Moreover, we show that coexpression of GPCRs with signal transduction components in Sf9 cells can also be applied to the characterization of other constitutively active receptors, for example, the formyl peptide receptor and beta(2)-adrenoceptor. C1 [Schneider, Erich H.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Seifert, Roland] Hannover Med Sch, Inst Pharmacol, D-3000 Hannover, Germany. RP Schneider, EH (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Schneider, Erich/B-9051-2016 OI Schneider, Erich/0000-0002-7905-4276 NR 28 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-381296-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 485 BP 527 EP 557 DI 10.1016/S0076-6879(10)85028-1 PG 31 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSI08 UT WOS:000284508700028 PM 21050935 ER PT B AU Espey, MG Chen, Q Sun, AY Kim, HS Padayatty, S Wang, YH Tu, HB Margolis, S Levine, M AF Espey, Michael Graham Chen, Qi Sun, Andrew Y. Kim, Hee Sung Padayatty, Sebastian Wang, Yaohui Tu, Hongbin Margolis, Sam Levine, Mark BE Das, DK TI Methodologies in the Use, Collection, and Analysis of Ascorbate SO METHODS IN REDOX SIGNALING LA English DT Article; Book Chapter ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TRANSITION-METAL IONS; VITAMIN-C; DEHYDROASCORBIC ACID; HYDROGEN-PEROXIDE; ELECTROCHEMICAL DETECTION; FREE-RADICALS; HUMAN PLASMA; ELECTRON-TRANSFER; CELL-CULTURE AB Ascorbate has long been recognized as an essential cofactor in enzyme catalyzed hydroxylation reactions. Despite intensive interest, its putative contribution as either an antioxidant or modulator of redox signaling remains a point of debate. Study has been hampered by difficulties in the application of ascorbate in cell culture models as well as its collection and analysis. This chapter offers the reader a general framework to address these issues. C1 [Espey, Michael Graham; Chen, Qi; Sun, Andrew Y.; Kim, Hee Sung; Padayatty, Sebastian; Wang, Yaohui; Tu, Hongbin; Margolis, Sam; Levine, Mark] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Espey, MG (reprint author), NIDDK, Mol & Clin Nutr Sect, NIH, 10-4D52,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 NR 53 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA BN 978-1-934854-06-8 PY 2010 BP 24 EP 30 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOE97 UT WOS:000276405600005 ER PT B AU Lam, PY Chang, AHK Cadenas, E Han, D AF Lam, Philip Y. Chang, Allen H. K. Cadenas, Enrique Han, Derick BE Das, DK TI Redox Signaling Molecules in and from Mitochondria SO METHODS IN REDOX SIGNALING LA English DT Article; Book Chapter ID NITRIC-OXIDE SYNTHASE; HYDROGEN-PEROXIDE PRODUCTION; SUPEROXIDE ANION; HORSERADISH-PEROXIDASE; INTERMEMBRANE SPACE; SKELETAL-MUSCLE; RELEASE; PEROXYNITRITE; GLUTATHIONE; NEUTROPHILS AB Mitochondria are major cellular sources of reactive oxygen- (H(2)O(2) and O(2)(center dot-)) and nitrogen ((center dot)NO and ONOO(-)) species. Reactive oxygen and nitrogen species released from mitochondria are involved in the regulation of the cellular redox state and redox-sensitive signaling pathways. Increased ROS and RNS generation from mitochondria can result in protein post-translational redox modifications (i.e. nitration, nitrosylation, disulfide bond formation) of both cytoplasmic and mitochondrial proteins, which can modulate protein activity. Several methods for detecting major redox-signaling molecules generated from mitochondria (O(2)(center dot-), H(2)O(2), and (center dot)NO) and the protein post-translational modifications caused by these species are described. C1 [Lam, Philip Y.; Cadenas, Enrique] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA. [Chang, Allen H. K.] NHLBI, NIH, Bethesda, MD 20824 USA. [Han, Derick] Univ So Calif, Keck Sch Med, Res Ctr Liver Dis, Los Angeles, CA 90089 USA. RP Lam, PY (reprint author), Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, 1985 Zonal Ave, Los Angeles, CA 90089 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA BN 978-1-934854-06-8 PY 2010 BP 242 EP 248 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOE97 UT WOS:000276405600033 ER PT B AU Mok, SC Stanley, MP Tsuda, H Birrer, MJ AF Mok, Samuel C. Stanley, Michael P. Tsuda, Hiroshi Birrer, Michael J. BE Hayat, MA TI Identification of Biomarkers for Clear Cell Ovarian Adenocarcinoma SO METHODS OF CANCER DIAGNOSIS, THERAPY, AND PROGNOSIS, VOL 6: OVARIAN CANCER, RENAL CANCER, UROGENITARY TRACT CANCER, URINARY BLADDER CANCER, CERVICAL UTERINE CANCER, SKIN CANCER, LEUKEMIA, MULTIPLE MYELOMA AND SARCOMA SE Methods of Cancer Diagnosis Therapy and Prognosis LA English DT Article; Book Chapter ID GENE-EXPRESSION; HISTOLOGICAL TYPES; POOR-PROGNOSIS; CARCINOMA; CANCER; RESISTANCE; PROTEIN; THERAPY C1 [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Stanley, Michael P.; Birrer, Michael J.] NCI, Bethesda, MD 20892 USA. [Tsuda, Hiroshi] Osaka City Gen Hosp, Dept Obstet & Gynecol, Osaka 5340021, Japan. RP Mok, SC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-2917-1 J9 METHODS CANCER DIAGN PY 2010 VL 6 BP 5 EP 12 D2 10.1007/978-90-481-2918-8 PG 8 WC Oncology; Medicine, General & Internal SC Oncology; General & Internal Medicine GA BNL22 UT WOS:000274847000001 ER PT J AU Shen, Y Cooper, GF AF Shen, Y. Cooper, G. F. TI A New Prior for Bayesian Anomaly Detection Application to Biosurveillance SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Anomaly detection; biosurveillance; Bayesian methods; prior probability distributions; efficient inference ID HIDDEN MARKOV-MODELS; OUTBREAKS AB Objectives: Bayesian anomaly detection computes posterior probabilities of anomalous events by combining prior beliefs and evidence from data. However, the specification of prior probabilities can be challenging. This paper describes a Bayesian prior in the context of disease outbreak detection. The goal is to provide a meaningful, easy-to-use prior that yields a posterior probability of an outbreak that performs at least as well as a standard frequentist approach. If this goal is achieved, the resulting posterior could be usefully incorporated into a decision analysis about how to act in light of a possible disease outbreak. Methods: This paper describes a Bayesian method for anomaly detection that combines learning from data with a semi-informative prior probability over patterns of anomalous events. A univariate version of the algorithm is presented here for ease of illustration of the essential ideas. The paper describes the algorithm in the context of disease-outbreak detection, but it is general and can be used in other anomaly detection applications. For this application, the semi-informative prior specifies that an increased count over baseline is expected for the variable being monitored, such as the number of respiratory chief complaints per day at a given emergency department. The semi-informative prior is derived based on the baseline prior, which is estimated from using historical data. Results: The evaluation reported here used semi-synthetic data to evaluate the detection performance of the proposed Bayesian method and a control chart method, which is a standard frequentist algorithm that is closest to the Bayesian method in terms of the type of data it uses. The disease-outbreak detection performance of the Bayesian method was statistically significantly better than that of the control chart method when proper baseline periods were used to estimate the baseline behavior to avoid seasonal effects. When using longer baseline periods, the Bayesian method performed as well as the control chart method. The time complexity of the Bayesian algorithm is linear in the number of the observed events being monitored, due to a novel, closed-form derivation that is introduced in the paper. Conclusions: This paper introduces a novel prior probability for Bayesian outbreak detection that is expressive, easy-to-apply, computationally efficient, and performs as well or better than a standard frequentist method. C1 [Shen, Y.] NIH, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. [Cooper, G. F.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA USA. RP Shen, Y (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Bldg 38A,9N912A, Bethesda, MD 20894 USA. EM yanna.shen@nih.gov FU National Science Foundation [IIS-0325581] FX This research was funded by a grant from the National Science Foundation (NSF IIS-0325581). We thank Bill Hogan for applying his BARD systeill to generate SiIllUlated cases of anthrax that were used in the evaluation, and we thank John Levander for his assistance in using those cases. NR 38 TC 4 Z9 4 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2010 VL 49 IS 1 BP 44 EP 53 DI 10.3414/ME09-01-0008 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 550MI UT WOS:000274131600006 PM 20027381 ER PT J AU Pasquali, P Thornton, AM Vendetti, S Pistoia, C Petrucci, P Tarantino, M Pesciaroli, M Ruggeri, F Battistoni, A Shevach, EM AF Pasquali, Paolo Thornton, Angela M. Vendetti, Silvia Pistoia, Claudia Petrucci, Paola Tarantino, Michela Pesciaroli, Michele Ruggeri, Franco Battistoni, Andrea Shevach, Ethan M. TI CD4+CD25+T regulatory cells limit effector T cells and favor the progression of brucellosis in BALB/c mice SO MICROBES AND INFECTION LA English DT Article DE Immunology; Regulatory T cells; Brucella; Immune response; Mouse model ID CUTTING EDGE; IN-VIVO; IMMUNITY; ABORTUS; INFECTION; TUBERCULOSIS; SUPPRESSION; CLEARANCE; TOLERANCE; PATHOLOGY AB Brucellosis is one of the most common bacterial zoonoses worldwide. Infection is usually chronic and sometimes lifelong. Different mechanisms can be postulated as to the basis for the induction of the chronic status of brucellosis, but a comprehensive knowledge is still lacking. Here, we carried out a series of experiments in order to assess if the persistence of Brucella abortus could be ascribed to the effect of a down regulation of the immune response due to activity of regulatory T cells. We demonstrate that CD4 + CD25 + T regulatory cells are able to limit the effectiveness of CD4 + T cells and are able to favor the maintenance and the progression of B. abortus infection. (C) 2009 Elsevier Masson SAS. All rights reserved. C1 [Pasquali, Paolo; Pistoia, Claudia; Petrucci, Paola; Tarantino, Michela; Pesciaroli, Michele; Ruggeri, Franco] Ist Super Sanita, Dept Food Safety & Vet Publ Hlth, I-00161 Rome, Italy. [Thornton, Angela M.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Vendetti, Silvia] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. [Battistoni, Andrea] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy. RP Pasquali, P (reprint author), Ist Super Sanita, Dept Food Safety & Vet Publ Hlth, Viale Regina Elena 299, I-00161 Rome, Italy. EM paolo.pasquali@iss.it RI Ruggeri, Franco/B-5707-2013; Pesciaroli, Michele/K-4422-2014; VENDETTI, SILVIA/M-4369-2015; Battistoni, Andrea/A-4778-2016 OI Pesciaroli, Michele/0000-0002-2092-8899; VENDETTI, SILVIA/0000-0002-8443-496X; Battistoni, Andrea/0000-0003-4085-7917 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases; Istituto Superiore di Sanita FX This work was partly supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. P.Pasquali and A. Battistoni received support from an intramural research project funded by Istituto Superiore di Sanita, under the Italy-USA research collaboration agreement. NR 30 TC 11 Z9 13 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2010 VL 12 IS 1 BP 3 EP 10 DI 10.1016/j.micinf.2009.09.005 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 547DG UT WOS:000273865200002 PM 19772948 ER PT J AU Hong, WZ Peng, DX Rivera, M Gu, XX AF Hong, Wenzhou Peng, Daxin Rivera, Maritza Gu, Xin-Xing TI Protection against nontypeable Haemophilus influenzae challenges by mucosal vaccination with a detoxified lipooligosaccharide conjugate in two chinchilla models SO MICROBES AND INFECTION LA English DT Article DE Mucosal immunization; Nontypeable Haemophilus influenzae; Chinchilla models; Lipooligosaccharide conjugate vaccine ID OUTER-MEMBRANE PROTEIN; ACUTE OTITIS-MEDIA; NASOPHARYNGEAL COLONIZATION; STREPTOCOCCUS-PNEUMONIAE; INTRANASAL IMMUNIZATION; ANTIBODIES; CLEARANCE; EFFICACY; P6 AB Otitis media (OM) can occur following outset of upper respiratory tract infections. Inhibition of bacterial colonization in nasopharynx (NP) by mucosal vaccination may prevent OM by reducing bacterial invasion of the middle ears (MEs). In this study, 80 chinchillas were intranasally (i.n.) immunized with a detoxified lipooligosaccharide (dLOS)-tetanus toxoid conjugate vaccine of nontypeable Haemophilus influenzae (NTHi) mixed with cholera toxin (CT) or CT alone. All vaccinated animals responded with elevated levels of mucosal and serum anti-LOS antibodies. Two weeks after the last immunization, 40 chinchillas were challenged i.n. with NTHi to evaluate NP colonization and ME infection while the rest of the animals were challenged transbullarly (T.B.) to examine the development of OM. Compared to the control group, the vaccination inhibited not only bacterial colonization in NP and transmission to MEs in the i.n. challenge group but also bacterial colonization in NP and transmission to unchallenged ears in the T.B. challenge group. Though no difference was found in the challenged ears of either group right after the T.B. challenge, an early clearance of NTHi from NP and unchallenged ears as well as less severity of OM in the unchallenged cars were observed in vaccinated animals. Current results along with our previous data indicate that mucosal vaccination is capable of inhibiting NTHi NP colonization and preventing OM occurrence in chinchillas; the i.n. challenge model is preferable for testing the mucosal vaccines while the T.B. challenge model is superior for testing the systemic vaccines. Published by Elsevier Masson SAS. C1 [Hong, Wenzhou; Peng, Daxin; Rivera, Maritza; Gu, Xin-Xing] Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, Rockville, MD 20850 USA. RP Gu, XX (reprint author), 5 Res Court,Room 2A31, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov FU NIH/ NIDCD FX We thank Dr. M.A. Apicella for providing strains and Dr. S. Yu for assisting in the animal challenge. This research was supported by the Intramural Research Program of the NIH/ NIDCD. NR 30 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2010 VL 12 IS 1 BP 11 EP 18 DI 10.1016/j.micinf.2009.09.006 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 547DG UT WOS:000273865200003 PM 19782149 ER PT B AU Joy, DA AF Joy, Deirdre A. BE Xu, J TI Population Genetics of Human Malaria Parasites SO MICROBIAL POPULATION GENETICS LA English DT Article; Book Chapter ID PLASMODIUM-VIVAX MALARIA; MITOCHONDRIAL GENOME; SELECTIVE SWEEPS; SOUTH-AMERICA; CYTOCHROME-B; FALCIPARUM; EVOLUTION; RESISTANCE; DIVERSITY; SEQUENCE AB Genetic diversity, population structure, and evolutionary history of malaria parasites are among the factors that influence our ability to identify genes contributing to drug resistance, parasite development, and disease pathogenesis. These factors also have an impact on vaccine and drug development, parasite source tracking, and the formulation of other disease prevention and control measures. For example, a highly polymorphic parasite population will contain ample genetic diversity capable of generating drug resistance genotypes at an accelerated rate; while the presence of homogeneous parasite populations should aid in the development of an effective malaria vaccine. Malaria research has entered the post-genomic era, and population genomics, the study of sequence variation across the genome, has begun to shed light on the relative importance of mutation, recombination, natural selection and genetic drift in shaping genetic variation in this important human parasite. C1 NIAID, Parasitol & Int Programs Branch, Div Microbiol & Infect Dis, NIH,DHHS, Bethesda, MD 20892 USA. RP Joy, DA (reprint author), NIAID, Parasitol & Int Programs Branch, Div Microbiol & Infect Dis, NIH,DHHS, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM djoy@mail.nih.gov NR 51 TC 0 Z9 0 U1 0 U2 1 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-59-2 PY 2010 BP 159 EP 165 PG 7 WC Microbiology SC Microbiology GA BOU20 UT WOS:000277617100010 ER PT J AU Warren, A Cogger, VC Arias, IM Mccuskey, RS Le Couteur, DG AF Warren, Alessandra Cogger, Victoria C. Arias, Irwin M. Mccuskey, Robert S. Le Couteur, David G. TI Liver Sinusoidal Endothelial Fenestrations in Caveolin-1 Knockout Mice SO MICROCIRCULATION LA English DT Article DE fenestrations; fenestrae; sinusoidal endothelial cell; liver; hepatic; caveolin-1; knockout mouse; electron microscopy; immunogold ID RAT-LIVER; HEPATIC MICROCIRCULATION; REGULATORY MECHANISMS; GROWTH-FACTOR; CELLS; PERMEABILITY; CYTOSKELETON; CONTRACTION; SYSTEM; SIEVE AB P>Objective: Fenestrations are pores in the liver sinusoidal endothelium that facilitate the transfer of particulate substrates between the sinusoidal lumen and hepatocytes. Fenestrations express caveolin-1 and have structural similarities to caveolae, therefore might be a form of caveolae and caveolin-1 may be integral to fenestration structure and function. Therefore, fenestrations were studied in the livers of caveolin-1 knockout mice. Methods: Scanning, transmission and immunogold electron microscopic techniques were used to study the liver sinusoidal endothelium and other tissues in caveolin-1 knockout and wild-type mice. Results: Comparison of fenestrations in wild-type and knockout mice did not reveal any differences on either scanning or transmission electron microscopy. The diameter of the fenestrations was not significantly different (74 +/- 13 nm knockout mice vs 78 +/- 12 nm wild-type mice) nor was the fenestration porosity (6.5 +/- 2.1 knockout vs 7.3 +/- 2.4% wild-type mice). In contrast, adipocytes and blood vessels in other tissues lacked caveolae in the knockout mice. Caveolin-1 immunogold of livers of wild-type mice indicated sparse expression in sinusoidal endothelial cells. Conclusions: The normal structure of fenestrations in the liver sinusoidal endothelium is not dependent upon caveolin-1 and fenestrations are not a form of caveolae. C1 [Warren, Alessandra; Cogger, Victoria C.; Le Couteur, David G.] Univ Sydney, Ctr Educ & Res Ageing, Sydney, NSW 2139, Australia. [Warren, Alessandra; Cogger, Victoria C.; Le Couteur, David G.] Univ Sydney, ANZAC Res Inst, Sydney, NSW 2139, Australia. [Warren, Alessandra; Cogger, Victoria C.; Le Couteur, David G.] Concord RG Hosp, Sydney, NSW 2139, Australia. [Arias, Irwin M.] NICHHD, Unit Cellular Polar, Cell Biol & Metab Program, Bethesda, MD 20892 USA. [Mccuskey, Robert S.] Univ Arizona, Coll Med, Dept Cell Biol & Anat, Tucson, AZ USA. RP Le Couteur, DG (reprint author), Univ Sydney, Ctr Educ & Res Ageing, Sydney, NSW 2139, Australia. EM d.lecouteur@usyd.edu.au FU Australian National Health and Medical Research Council; Ageing and Alzheimers Research Foundation FX The study was supported by the Australian National Health and Medical Research Council and the Ageing and Alzheimers Research Foundation (a Division of the Medical Foundation of the University of Sydney). We thank Dr Robert Parton, University of Queensland for his generous provision of the caveolin-1 knockout mice used in this study. NR 36 TC 11 Z9 12 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PY 2010 VL 17 IS 1 BP 32 EP 38 DI 10.1111/j.1549-8719.2009.00004.x PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 553AI UT WOS:000274336400004 PM 20141598 ER PT J AU Kim, CH AF Kim, Chang Hee BE Gusev, Y TI WHO DUNIT? MICRORNAS INVOLVED IN PROSTATE CANCER SO MICRORNA PROFILING IN CANCER: A BIOINFORMATICS PERSPECTIVE LA English DT Article; Book Chapter ID MICROPROCESSOR COMPLEX; CELL LINES; EXPRESSION; RNA; GENE; TARGETS; CLASSIFICATION; SIGNATURE; CARCINOMA; LOCUS AB Either as causative agents or responsive elements, microRNAs are differentially expressed in prostate cancer. However, microRNA profiling in prostate cancer has been fraught with discrepancies across studies owing to differences in the profiling technologies used, and in the prostate cancer samples that have been miR-125, miR-100, let-7 seem to recur as differentially expressed microRNAs in prostate tumors compared to normal prostate tissue. The validated targets of some of the differentially expressed microRNAs are either proliferation genes or pro-apoptotic/growth inhibitory genes, suggesting their implication in cancer. Clearly, microRNA profiling technologies need to be better standardized and validated accurately in order to facilitate the discovery of diagnostic and prognostic molecular biomarkers for prostate cancer. microRNAs are also differentially expressed between androgen responsive and androgen refractory prostate cancers, although again there are only a few overlaps across studies. Androgen also seems to regulate the expression of microRNAs. The discovery of a microRNA-mediated androgen signaling pathway may prove invaluable to the treatment of androgen-refractory prostate cancer. C1 NCI, SAIC Frederick Inc, Lab Mol Technol, Adv Technol Program, Frederick, MD 21702 USA. RP Kim, CH (reprint author), NCI, SAIC Frederick Inc, Lab Mol Technol, Adv Technol Program, Frederick, MD 21702 USA. NR 48 TC 0 Z9 0 U1 0 U2 1 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-9-81426-754-0 PY 2010 BP 95 EP 115 PG 21 WC Biochemistry & Molecular Biology; Oncology; Genetics & Heredity; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Oncology; Genetics & Heredity; Mathematical & Computational Biology GA BTX51 UT WOS:000288367000006 ER PT J AU Huppi, K Volfovsky, N Wahlberg, B Stephens, RM Caplen, NJ AF Huppi, Konrad Volfovsky, Natalia Wahlberg, Brady Stephens, Robert M. Caplen, Natasha J. BE Gusev, Y TI MIROME ARCHITECTURE AND GENOMIC INSTABILITY SO MICRORNA PROFILING IN CANCER: A BIOINFORMATICS PERSPECTIVE LA English DT Article; Book Chapter ID RETROVIRAL INSERTIONAL MUTAGENESIS; B-CELL LEUKEMIA; GENE IDENTIFICATION; MICRORNA CISTRON; DELETED REGION; LUNG-CANCER; BXH2 MICE; LOCUS; ACTIVATION; LYMPHOMA AB Genomic instability has been observed in many different types of cancers. While genetic alterations often cover a large spectrum of genomic events including gross rearrangement or amplification or deletion of chromosomal regions, some alterations are minimally detectable including small microsatellite or indel mutations and retroviral integration. In fact, the study of events associated with genomic instability has led to the discovery of many new and important genes associated with critical regulatory pathways. More recently, small regulatory RNAs or microRNAs have been found to reside throughout the genome and it has been suggested that such genetic alterations could also target microRNAs. In this chapter we will examine genomic instability that may alter human or mouse microRNA expression and function. Using both computational and experimental approaches, we outline possible associations between regions of genomic instability and novel microRNA candidates or already established and known microRNAs. C1 [Huppi, Konrad; Wahlberg, Brady; Caplen, Natasha J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Volfovsky, Natalia; Stephens, Robert M.] NCI Frederick, Adv Biomed Comp Ctr, Adv Technol Program, SAIC Frederick Inc,NIH, Frederick, MD USA. RP Huppi, K (reprint author), NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NR 53 TC 0 Z9 0 U1 0 U2 1 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-9-81426-754-0 PY 2010 BP 133 EP 147 PG 15 WC Biochemistry & Molecular Biology; Oncology; Genetics & Heredity; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Oncology; Genetics & Heredity; Mathematical & Computational Biology GA BTX51 UT WOS:000288367000008 ER PT S AU Sackett, DL Werbovetz, KA Morrissette, NS AF Sackett, Dan L. Werbovetz, Karl A. Morrissette, Naomi S. BE Wilson, L Correia, JJ TI Isolating Tubulin from Nonneural Sources SO MICROTUBULES, IN VITRO: MICROTUBULES, IN VITRO SE Methods in Cell Biology LA English DT Review; Book Chapter ID YEAST SACCHAROMYCES-CEREVISIAE; BREAST-CANCER CELLS; ASSEMBLY IN-VITRO; ALPHA-TUBULIN; BETA-TUBULIN; TETRAHYMENA-THERMOPHILA; DINITROANILINE HERBICIDE; DROSOPHILA-MELANOGASTER; MASS-SPECTROMETRY; RESISTANT CELLS AB Tubulin is a highly conserved, negatively charged protein that is found in essentially all eukaryotic cells. These properties ensure that isolation protocols successful in one system will likely work, with a few modifications, in most systems. Tubulin has been isolated most frequently from mammalian brain, and the main difference encountered in other systems versus brain is that tubulin is much less abundant in nearly all other sources than it is in brain. This means that attempting to purify tubulin by direct polymerization from a homogenate will often fail or be quite inefficient. However, the conservation of negative charge on tubulin means that an initial ion exchange step can be used to both purify and concentrate the protein from most systems. Polymerization-competent tubulin can usually be obtained by inducing polymerization in the salt eluate from the ion exchange step. We describe protocols for this procedure and describe its application to a number of vertebrate, fungal, protozoal, and plant sources. C1 [Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Werbovetz, Karl A.] Ohio State Univ, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. [Morrissette, Naomi S.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. RP Sackett, DL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA. RI Werbovetz, Karl/E-4290-2011 FU Intramural NIH HHS; NIAID NIH HHS [AI067981, R01 AI067981, R01 AI067981-05] NR 62 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-374815-7 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2010 VL 95 BP 17 EP 32 DI 10.1016/S0091-679X(10)95002-4 PG 16 WC Cell Biology SC Cell Biology GA BPF84 UT WOS:000278776500002 PM 20466127 ER PT S AU Goodson, HV Gregoretti, IV AF Goodson, Holly V. Gregoretti, Ivan V. BE Wilson, L Correia, JJ TI Using Computational Modeling to Understand Microtubule Dynamics: A Primer for Cell Biologists SO MICROTUBULES, IN VITRO: MICROTUBULES, IN VITRO SE Methods in Cell Biology LA English DT Review; Book Chapter ID LATERAL CAP MODEL; MONTE-CARLO; INSTABILITY; SIMULATION; INSIGHTS; KINETICS; LATTICE AB Experimental cell biology, biochemistry, and structural biology have provided a wealth of information about microtubule function and mechanism, but we are reaching a limit as to what can be understood from experiment alone. Standard biochemical approaches are not sufficient to make quantitative predictions about microtubule behavior, and they are limited in their ability to test existing conceptual models of microtubule mechanism. Because microtubules are so complex, achieving a deep understanding of microtubule behavior and mechanism will require the input of mathematical and computational modeling. However, this type of analysis can be daunting to the uninitiated. The purpose of this chapter is to provide a straightforward introduction to the various types of modeling and how they can be used to study microtubule function, dynamics, and mechanism. C1 [Goodson, Holly V.] Univ Notre Dame, Dept Chem & Biochem, Ctr Study Biocomplex, Notre Dame, IN 46556 USA. [Gregoretti, Ivan V.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Goodson, HV (reprint author), Univ Notre Dame, Dept Chem & Biochem, Ctr Study Biocomplex, Notre Dame, IN 46556 USA. NR 29 TC 3 Z9 3 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-374815-7 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2010 VL 95 BP 175 EP 188 DI 10.1016/S0091-679X(10)95010-3 PG 14 WC Cell Biology SC Cell Biology GA BPF84 UT WOS:000278776500010 PM 20466135 ER PT S AU Begaye, A Sackett, DL AF Begaye, Adrian Sackett, Dan L. BE Wilson, L Correia, JJ TI Measurement of Ligand Binding to Tubulin by Sulfhydryl Reactivity SO MICROTUBULES, IN VITRO: MICROTUBULES, IN VITRO SE Methods in Cell Biology LA English DT Review; Book Chapter ID PODOPHYLLOTOXIN; POLYMERIZATION; CYSTEINE; PROBE; SITE AB Ligand binding can induce shifts in protein conformation. In the case of tubulin, these drug-induced confirmational changes can prevent or stabilize microtubule polymerization. 5',5'-Dithiobis(2-nitrobenzoate) (DTNB) reacts with free and accessible sulfhydryls and stoichiometrically produces a detectable product, which allows an exact measurement of reacted thiols. Since binding of small ligands may alter conformational dynamics, it may also affect the reactivity of thiols on tubulin. Differences in DTNB reactivity with thiols upon ligand binding can therefore be used to deduce binding characteristics. We will describe two methods that use tubulin cysteine reactivity with DTNB in the presence of drug to define ligand-binding characteristics. C1 [Begaye, Adrian; Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Begaye, A (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 15 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-374815-7 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2010 VL 95 BP 391 EP 403 DI 10.1016/S0091-679X(10)95021-8 PG 13 WC Cell Biology SC Cell Biology GA BPF84 UT WOS:000278776500021 PM 20466146 ER PT S AU Kiris, E Ventimiglia, D Feinstein, SC AF Kiris, Erkan Ventimiglia, Donovan Feinstein, Stuart C. BE Wilson, L Correia, JJ TI Quantitative Analysis of MAP-Mediated Regulation of Microtubule Dynamic Instability In Vitro-Focus on Tau SO MICROTUBULES, IN VITRO: MICROTUBULES, IN VITRO SE Methods in Cell Biology LA English DT Review; Book Chapter ID DARK-FIELD MICROSCOPY; GROWTH CONE MOTILITY; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; INDIVIDUAL MICROTUBULES; LIVING CELLS; PROTEIN-TAU; NEURODEGENERATIVE DISORDERS; ANTISENSE OLIGONUCLEOTIDES; NEUROFIBRILLARY TANGLES AB The regulation of microtubule growing and shortening dynamics is essential for proper cell function and viability, and microtubule-associated proteins (MAPs) such as the neural protein tau are critical regulators of these dynamic processes. Further, we and our colleagues have proposed that misregulation of microtubule dynamics may contribute to tau-mediated neuronal cell death and dementia in Alzheimer's and related diseases. In the first part of this chapter, we present a general background on microtubule dynamics and then focus in on tau. We review the literature on the roles of tau in normal neuronal cell biology, the tau structure function relationship, regulatory mechanisms influencing tau action, and pathological tau action, including normal and aberrant regulation of microtubule dynamics. In the second part of this chapter, we present detailed protocols for various in vitro procedures often used in studying tau-mediated regulation of microtubule dynamics, including purification and characterization of necessary reagents, microtubule assembly assays, and microtubule dynamics assays. Importantly, these assays are readily adaptable to examine other regulators of microtubule dynamics besides tau. In the final analysis, in vitro analyses of MAP-mediated regulation of microtubule dynamics will provide extremely valuable insights into our understanding of normal and pathological cell biology. C1 [Kiris, Erkan] NCI, TRUE Res Fdn, Frederick, MD 21702 USA. [Ventimiglia, Donovan] Rockefeller Univ, New York, NY 10065 USA. [Feinstein, Stuart C.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA USA. [Feinstein, Stuart C.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA USA. RP Kiris, E (reprint author), NCI, TRUE Res Fdn, Frederick, MD 21702 USA. NR 122 TC 6 Z9 6 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 0091-679X BN 978-0-12-374815-7 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2010 VL 95 BP 481 EP 503 DI 10.1016/S0091-679X(10)95024-3 PG 23 WC Cell Biology SC Cell Biology GA BPF84 UT WOS:000278776500024 PM 20466149 ER PT S AU Li, HL Cao, YY Dill, JC AF Li, Huanlin Cao, Yanyan Dill, Jeffrey C. GP IEEE TI Analysis of Error-Prone Patterns for LDPC Codes under Belief Propagation Decoding SO MILITARY COMMUNICATIONS CONFERENCE, 2010 (MILCOM 2010) SE IEEE Military Communications Conference LA English DT Proceedings Paper CT MILCOM Military Communications Conference CY OCT 31-NOV 03, 2010 CL San Jose, CA DE LDPC code; error floor; belief propagation (BP) algorithm; iterative decoding; trapping set; error-prone pattern; two-stage decoder; pesudo-cycle ID PARITY-CHECK CODES; FLOOR AB Lowering the error floor of LDPC codes is extremely attractive to some systems, such as deep space communication systems and storage systems, which desire very low error rates. The error floor phenomenon of LDPC codes, which is associated with their message passing decoding algorithms, is mainly caused by some unfavorable combinatorial characteristics (or error-prone patterns) of LDPC codes. In this paper, a mathematical analysis method which enables the identification of some significant features of error-prone patterns is presented with the help of the beliefs passed in their decoders. Based on the analysis, an improved decoder is proposed which can effectively deal with the traversable trapping sets and achieve significantly improved error floor performance compared with current decoders. More importantly, this proposed decoder does not require the information of all the possible trapping sets of an individual LDPC code when correcting the error bits in its trapping sets. C1 [Li, Huanlin; Dill, Jeffrey C.] Ohio Univ, Sch EECS, Russ Coll Engn, Athens, OH 45701 USA. [Cao, Yanyan] NIH, NIDDK, Bethesda, MD USA. RP Li, HL (reprint author), Ohio Univ, Sch EECS, Russ Coll Engn, Athens, OH 45701 USA. EM Hl119803@ohio.edu; Caoy4@mail.nih.gov; dill@ohio.edu NR 28 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2155-7578 BN 978-1-4244-8180-4 J9 IEEE MILIT COMMUN C PY 2010 BP 2056 EP 2061 PG 6 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA BTQ21 UT WOS:000287747200193 ER PT B AU Rostovtseva, TK AF Rostovtseva, Tatiana K. BE Svensson, OL TI CONTROL OF MITOCHONDRIAL OUTER MEMBRANE PERMEABILITY: VDAC REGULATION BY DIMERIC TUBULIN AND CYTOSOLIC PROTEINS SO MITOCHONDRIA: STRUCTURE, FUNCTIONS AND DYSFUNCTIONS SE Cell Biology Research Progress LA English DT Article; Book Chapter ID DEPENDENT ANION CHANNEL; ADENINE-NUCLEOTIDE TRANSPORT; GLYCOGEN-SYNTHASE KINASE-3; CELL-DEATH; TRANSITION PORE; INDUCED APOPTOSIS; SUBCELLULAR-LOCALIZATION; INTACT MITOCHONDRIA; HEXOKINASE BINDING; NEUROSPORA-CRASSA C1 [Rostovtseva, Tatiana K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bethesda, MD USA. RP Rostovtseva, TK (reprint author), NICHD, NIH, 9000 Rockville Pike,Bldg 9,Room 1E-106, Bethesda, MD 20892 USA. EM rostovtt@mail.nih.gov NR 118 TC 3 Z9 3 U1 0 U2 1 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-61668-346-7 J9 CELL BIO RES PROG PY 2010 BP 607 EP 633 PG 27 WC Cell Biology SC Cell Biology GA BTG89 UT WOS:000286916800013 ER PT B AU Sackett, DL AF Sackett, Dan L. BE Svensson, OL TI EVOLUTION AND COEVOLUTION OF TUBULIN'S CARBOXY-TERMINAL TAILS AND MITOCHONDRIA SO MITOCHONDRIA: STRUCTURE, FUNCTIONS AND DYSFUNCTIONS SE Cell Biology Research Progress LA English DT Article; Book Chapter ID DEPENDENT ANION CHANNEL; MICROTUBULE-ASSOCIATED PROTEINS; ALPHA-BETA-TUBULIN; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; BINDING-SITE; POSTTRANSLATIONAL MODIFICATIONS; CRYSTAL-STRUCTURE; MEMBRANE TUBULIN; CREATINE-KINASE; OUTER-MEMBRANE C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA. RP Sackett, DL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA. NR 144 TC 4 Z9 4 U1 0 U2 2 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-61668-346-7 J9 CELL BIO RES PROG PY 2010 BP 789 EP 810 PG 22 WC Cell Biology SC Cell Biology GA BTG89 UT WOS:000286916800020 ER PT S AU Chang, CR Blackstone, C AF Chang, Chuang-Rung Blackstone, Craig BE Wei, YH Tzeng, CR Lee, HM TI Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1 SO MITOCHONDRIAL RESEARCH IN TRANSLATIONAL MEDICINE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th Conference of the Asian-Society-for-Mitochondrial-Research-and-Medicine CY OCT 30-NOV 01, 2009 CL Taipei Med Univ, Taipei, TAIWAN SP Asian Soc Mitochondrial Res & Med HO Taipei Med Univ DE mitochondria; fission; phosphorylation; sumoylation; dynamin; GTPase ID DOMINANT OPTIC ATROPHY; CELL-DEATH; PEROXISOMAL FISSION; MAMMALIAN-CELLS; GTPASE DRP1; FUSION; PHOSPHORYLATION; MORPHOLOGY; DIVISION; KINASE AB Mitochondria in cells comprise a tubulovesicular network shaped continuously by complementary fission and fusion events. The mammalian Drp1 protein plays a key role in fission, while Mfn1, Mfn2, and OPA1 are required for fusion. Shifts in the balance between these opposing processes can occur rapidly, indicating that modifications to these proteins may regulate mitochondrial membrane dynamics. We highlight posttranslational modifications of the mitochondrial fission protein Drp1, for which these regulatory mechanisms are best characterized. This dynamin-related GTPase undergoes a number of steps to mediate mitochondrial fission, including translocation from cytoplasm to the mitochondrial outer membrane, higher-order assembly into spirals, GTP hydrolysis associated with a conformational change and membrane deformation, and ultimately disassembly. Many of these steps may be influenced by covalent modification of Drp1. We discuss the dynamic nature of Drp1 modifications and how they contribute not only to the normal regulation of mitochondrial division, but also to neuropathologic processes. C1 [Chang, Chuang-Rung] Natl Tsing Hua Univ, Inst Biotechnol, Hsinchu, Taiwan. RP Blackstone, C (reprint author), Natl Inst Neurol Disorders & Stroke, Cellular Neurol Unit, Neurogenet Branch, NIH, Bldg 35,Room 2C-913,9000 Rockville Pike, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov RI Chang, Chuang-Rung /C-1815-2012 NR 40 TC 146 Z9 152 U1 5 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-803-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1201 BP 34 EP 39 DI 10.1111/j.1749-6632.2010.05629.x PG 6 WC Cell Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Cell Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BTN05 UT WOS:000287380500006 PM 20649536 ER PT J AU Chaconas, G Craig, N Curcio, MJ Deininger, P Feschotte, C Levin, H Rice, PA Voytas, DF AF Chaconas, George Craig, Nancy Curcio, M. Joan Deininger, Prescott Feschotte, Cedric Levin, Henry Rice, Phoebe A. Voytas, Daniel F. TI Meeting Report for Mobile DNA 2010 SO MOBILE DNA LA English DT Article AB An international conference on mobile DNA was held 24-28 April 2010 in Montreal, Canada. Sponsored by the American Society for Microbiology, the conference's goal was to bring together researchers from around the world who study transposition in diverse organisms using multiple experimental approaches. The meeting drew over 190 attendees and most contributed through poster presentations, invited talks and short talks selected from poster abstracts. The talks were organized into eight scientific sessions, which ranged in topic from the evolutionary dynamics of mobile genetic elements to transposition reaction mechanisms. Here we present highlights from the platform sessions with a focus on talks presented by the invited speakers. C1 [Chaconas, George] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. [Chaconas, George] Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada. [Craig, Nancy] Johns Hopkins Univ, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. [Craig, Nancy] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Curcio, M. Joan] Wadsworth Ctr, Ctr Med Sci, Albany, NY 12201 USA. [Deininger, Prescott] Tulane Univ, Tulane Canc Ctr, New Orleans, LA 70112 USA. [Feschotte, Cedric] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA. [Levin, Henry] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Rice, Phoebe A.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. [Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. RP Voytas, DF (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. EM voytas@umn.edu OI Deininger, Prescott/0000-0002-1067-3028; Curcio, M. Joan/0000-0001-5361-3909 FU NIGMS NIH HHS [R01 GM052072] NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1759-8753 J9 MOBILE DNA-UK JI Mob. DNA PY 2010 VL 1 AR 20 DI 10.1186/1759-8753-1-20 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA V28QJ UT WOS:000208695000020 PM 20735816 ER PT J AU Huda, A Marino-Ramirez, L Jordan, IK AF Huda, Ahsan Marino-Ramirez, Leonardo Jordan, I. King TI Epigenetic histone modifications of human transposable elements: genome defense versus exaptation SO MOBILE DNA LA English DT Article AB Background: Transposition is disruptive in nature and, thus, it is imperative for host genomes to evolve mechanisms that suppress the activity of transposable elements (TEs). At the same time, transposition also provides diverse sequences that can be exapted by host genomes as functional elements. These notions form the basis of two competing hypotheses pertaining to the role of epigenetic modifications of TEs in eukaryotic genomes: the genome defense hypothesis and the exaptation hypothesis. To date, all available evidence points to the genome defense hypothesis as the best explanation for the biological role of TE epigenetic modifications. Results: We evaluated several predictions generated by the genome defense hypothesis versus the exaptation hypothesis using recently characterized epigenetic histone modification data for the human genome. To this end, we mapped chromatin immunoprecipitation sequence tags from 38 histone modifications, characterized in CD4+ T cells, to the human genome and calculated their enrichment and depletion in all families of human TEs. We found that several of these families are significantly enriched or depleted for various histone modifications, both active and repressive. The enrichment of human TE families with active histone modifications is consistent with the exaptation hypothesis and stands in contrast to previous analyses that have found mammalian TEs to be exclusively repressively modified. Comparisons between TE families revealed that older families carry more histone modifications than younger ones, another observation consistent with the exaptation hypothesis. However, data from within family analyses on the relative ages of epigenetically modified elements are consistent with both the genome defense and exaptation hypotheses. Finally, TEs located proximal to genes carry more histone modifications than the ones that are distal to genes, as may be expected if epigenetically modified TEs help to regulate the expression of nearby host genes. Conclusions: With a few exceptions, most of our findings support the exaptation hypothesis for the role of TE epigenetic modifications when vetted against the genome defense hypothesis. The recruitment of epigenetic modifications may represent an additional mechanism by which TEs can contribute to the regulatory functions of their host genomes. C1 [Huda, Ahsan; Jordan, I. King] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Marino-Ramirez, Leonardo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Marino-Ramirez, Leonardo] Agr CORPOICA, Corp Colombiana Invest, Biotechnol & Bioind Ctr, Computat Biol & Bioinformat Unit, Bogota, Colombia. RP Jordan, IK (reprint author), Georgia Inst Technol, Sch Biol, 310 Ferst Dr, Atlanta, GA 30332 USA. EM king.jordan@biology.gatech.edu RI Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Intramural Research Program of the NIH; NLM; NCBI; Corporacion Colombiana de Investigacion Agropecuaria - CORPOICA; Alfred P Sloan Research Fellowship in Computational and Evolutionary Molecular Biology [BR-4839]; School of Biology at the Georgia Institute of Technology FX This research was supported in part by the Intramural Research Program of the NIH, NLM, NCBI. LMR is supported by Corporacion Colombiana de Investigacion Agropecuaria - CORPOICA. IKJ and graduate student AH were supported by an Alfred P Sloan Research Fellowship in Computational and Evolutionary Molecular Biology (BR-4839). AH was supported by the School of Biology at the Georgia Institute of Technology. The authors would like to thank Lee S Katz and Troy Hilley for helpful discussions and technical advice. The authors would also like to thank Keji Zhao and Chongzhi Zang for providing assistance with the procurement of their dataset. NR 41 TC 23 Z9 25 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1759-8753 J9 MOBILE DNA-UK JI Mob. DNA PY 2010 VL 1 AR 2 DI 10.1186/1759-8753-1-2 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA V28QJ UT WOS:000208695000002 PM 20226072 ER PT B AU Luo, J Chen, YD AF Luo, Jun Chen, Yidong BE Yegnasubramanian, S Isaacs, WB TI Use of Expression Microarrays in Cancer Research SO MODERN MOLECULAR BIOLOGY: APPROACHES FOR UNBIASED DISCOVERY IN CANCER RESEARCH SE Applied Bioinformatics and Biostatistics in Cancer Research LA English DT Article; Book Chapter ID OLIGONUCLEOTIDE ARRAY DATA; METHYLACYL-COA RACEMASE; HUMAN PROSTATE-CANCER; CONTROL MAQC PROJECT; GENE SET ENRICHMENT; BREAST-CANCER; QUALITY-CONTROL; DNA MICROARRAY; PROGNOSTIC CLASSIFICATION; MOLECULAR-MARKER AB Since its inception more than 15 years ago, the rapidly evolving array-based gene expression technology has been widely adopted and become an indispensable tool in cancer research. In this chapter, we will discuss the various platforms and the corresponding technical and analytical steps including study design, sample selection and processing, data generation and data analysis. We will identify and discuss key issues that may affect the reliability and precision of end-point array results, as well as common pitfalls that influence the interpretation of the analytical results. C1 [Luo, Jun] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. [Chen, Yidong] NCI, Bethesda, MD 20892 USA. RP Luo, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. EM jluo1@jhmi.edu; yidong@mail.nih.gov NR 77 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69744-4 J9 APPL BIOINF BIOSTAT JI Appl. Bioinf. Biostat. Canc. Res. PY 2010 BP 67 EP 85 DI 10.1007/978-0-387-69745-1_5 D2 10.1007/978-0-387-69745-1 PG 19 WC Oncology; Mathematical & Computational Biology SC Oncology; Mathematical & Computational Biology GA BQX46 UT WOS:000282062900005 ER PT J AU Gradowski, JF Jaffe, ES Warnke, RA Pittaluga, S Surti, U Gole, LA Swerdlow, SH AF Gradowski, Joel F. Jaffe, Elaine S. Warnke, Roger A. Pittaluga, Stefania Surti, Urvashi Gole, Leena A. Swerdlow, Steven H. TI Follicular lymphomas with plasmacytic differentiation include two subtypes SO MODERN PATHOLOGY LA English DT Article DE follicular lymphoma; fluorescence in situ hybridization; plasmacytic differentiation; B-cell lymphoma; cytogenetics ID MARGINAL ZONE LYMPHOMA; CENTER-CELL LYMPHOMA; MONOCYTOID B-CELLS; BCL6 TRANSLOCATIONS; TISSUE; EXPRESSION; COMPONENTS; T(14-18) AB Follicular lymphomas with plasmacytic differentiation were described more than two decades ago. However, the possibility that some of these reported cases are marginal zone lymphomas or composite lymphomas must be considered. In addition, it is also uncertain whether follicular lymphomas with plasmacytic differentiation have any unique cytogenetic or other features. Therefore, fluorescence immunophenotypic and interphase cytogenetic analysis of 14 well-characterized follicular lymphomas with plasmacytic differentiation was performed using a CD138 antibody to identify the plasma cells and with BCL2, BCL6, IGH@ and MALT1 break-apart probes and a chromosome 12 centromeric probe. CD10 was expressed in 12/14 cases, BCL6 in 12/12 cases and BCL2 in 12/14 cases. At least one cytogenetic abnormality was identified in 12/14 cases. The same abnormality was present in both the plasmacytic (CD138+) and non-plasmacytic (CD138-) component in all 10 evaluable cases. BCL2 rearrangements were present in seven cases ( 5 IGH@ rearranged, 1 IGH@-not rearranged, 1 IGH@-not evaluable), BCL6 rearrangement in two ( 1 also with BCL2/IGH@ rearrangement), +12 in 1, +MALT1 without +18 in 1, IGH@ rearrangement without other abnormalities in 1 and IGH@ rearranged or partially deleted in 1 case. No cases showed +BCL6 (3q27) or a MALT1 rearrangement. All six cases with an isolated BCL2 rearrangement had predominantly interfollicular plasmacytic cells whereas, 6/7 cases without the translocation had concentrations of intrafollicular or perifollicular plasmacytic cells (P<0.005), as did the case with BCL2 and BCL6 translocations. These results support the existence of bona fide follicular lymphomas with plasmacytic differentiation and support the clonal relationship of the neoplastic lymphoid and plasma cells in at least most of these cases. The differential distribution of the plasma cells, specifically in relation to the presence or absence of an isolated BCL2 rearrangement suggests that the latter cases may be distinctive, sharing some features with marginal zone lymphomas. Modern Pathology (2010) 23, 71-79; doi: 10.1038/modpathol.2009.146; published online 16 October 2009 C1 [Swerdlow, Steven H.] Univ Pittsburgh, Sch Med, Dept Pathol, UPMC Presbyterian,Div Hematopathol, Pittsburgh, PA 15213 USA. [Jaffe, Elaine S.; Pittaluga, Stefania] NCI, Dept Pathol, Bethesda, MD 20892 USA. [Warnke, Roger A.] Stanford Univ, Dept Pathol, Palo Alto, CA 94304 USA. [Surti, Urvashi; Gole, Leena A.] UPMC Magee Womens Hosp, Pittsburgh Cytogenet Lab, Pittsburgh, PA USA. RP Swerdlow, SH (reprint author), Univ Pittsburgh, Sch Med, Dept Pathol, UPMC Presbyterian,Div Hematopathol, Room G-335,200 Lothrop St, Pittsburgh, PA 15213 USA. EM swerdlowsh@upmc.edu NR 38 TC 17 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2010 VL 23 IS 1 BP 71 EP 79 DI 10.1038/modpathol.2009.146 PG 9 WC Pathology SC Pathology GA 539IV UT WOS:000273248500016 PM 19838161 ER PT J AU Mishra, SK Hoon, MA AF Mishra, Santosh K. Hoon, Mark A. TI Ablation of TrpV1 neurons reveals their selective role in thermal pain sensation SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Resiniferotoxin; TrpV1; Nociception; Pain; Thermal sensation ID CAPSAICIN RECEPTOR VR1; MAMMALIAN TASTE RECEPTORS; PRIMARY AFFERENT NEURONS; SENSORY NEURONS; DIRECT PHOSPHORYLATION; INTRATHECAL CAPSAICIN; VANILLOID RECEPTOR-1; NOCICEPTIVE NEURONS; HEAT; CHANNELS AB Here we make use of neural ablation to investigate the properties of the TrpV1-expressing neurons in the trigeminal and dorsal root ganglia of mice. Resiniferotoxin (RTX), a potent TrpV1 agonist, administered either by direct injection in the ganglion or intrathecally killed approximately 70% of TrpV1 cells and resulted in modest thermal analgesia. Interestingly, after carageenan injection in the hind paw, the analgesic effects of RTX were dramatically increased with mice now paradoxically showing far less response to heat applied at sites of inflammation. This additional carageenan and RTX-induced analgesia was transient, lasting less than 2 days, and likely resulted from deafferentation of remaining TrpV1 neurons. Remarkably, although RTX affected sensitivity to heat, mechanical sensitivity (both of normal and inflamed tissue) was completely unaltered by toxin-mediated silencing of the TrpV1 sensory input. Thus, our data demonstrate that TrpV1 neurons are selectively tuned nociceptors that mediate responses to thermal but not mechanical pain and insinuate a labeled line model for somatosensory coding. Published by Elsevier Inc. C1 [Mishra, Santosh K.; Hoon, Mark A.] NIDCR, Mol Genet Unit, Lab Sensory Biol, Bethesda, MD 20892 USA. RP Hoon, MA (reprint author), NIDCR, Mol Genet Unit, Lab Sensory Biol, NIH Bldg 49,Room 1A16,49 Convent Dr, Bethesda, MD 20892 USA. EM mark.hoon@nih.gov RI Mishra, Santosh/G-5145-2010 FU NIH; NIDCR FX We thank N. Ryba, T. Usdin, and S. Gutkind for helpful discussions and critical review of the manuscript. This work was supported by the intramural research program of the NIH, NIDCR. NR 41 TC 47 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN PY 2010 VL 43 IS 1 BP 157 EP 163 DI 10.1016/j.mcn.2009.10.006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 542VK UT WOS:000273526900016 PM 19853036 ER PT J AU Bozdagi, O Sakurai, T Papapetrou, D Wang, XB Dickstein, DL Takahashi, N Kajiwara, Y Yang, M Katz, AM Scattoni, ML Harris, MJ Saxena, R Silverman, JL Crawley, JN Zhou, Q Hof, PR Buxbaum, JD AF Bozdagi, Ozlem Sakurai, Takeshi Papapetrou, Danae Wang, Xiaobin Dickstein, Dara L. Takahashi, Nagahide Kajiwara, Yuji Yang, Mu Katz, Adam M. Scattoni, Maria Luisa Harris, Mark J. Saxena, Roheeni Silverman, Jill L. Crawley, Jacqueline N. Zhou, Qiang Hof, Patrick R. Buxbaum, Joseph D. TI Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication SO MOLECULAR AUTISM LA English DT Article AB Background: SHANK3 is a protein in the core of the postsynaptic density (PSD) and has a critical role in recruiting many key functional elements to the PSD and to the synapse, including components of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA), metabotropic glutamate (mGlu) and N-methyl-D-aspartic acid (NMDA) glutamate receptors, as well as cytoskeletal elements. Loss of a functional copy of the SHANK3 gene leads to the neurobehavioral manifestations of 22q13 deletion syndrome and/or to autism spectrum disorders. The goal of this study was to examine the effects of haploinsufficiency of full-length Shank3 in mice, focusing on synaptic development, transmission and plasticity, as well as on social behaviors, as a model for understanding SHANK3 haploinsufficiency in humans. Methods: We used mice with a targeted disruption of Shank3 in which exons coding for the ankyrin repeat domain were deleted and expression of full-length Shank3 was disrupted. We studied synaptic transmission and plasticity by multiple methods, including patch-clamp whole cell recording, two-photon time-lapse imaging and extracellular recordings of field excitatory postsynaptic potentials. We also studied the density of GluR1-immunoreactive puncta in the CA1 stratum radiatum and carried out assessments of social behaviors. Results: In Shank3 heterozygous mice, there was reduced amplitude of miniature excitatory postsynaptic currents from hippocampal CA1 pyramidal neurons and the input-output (I/O) relationship at Schaffer collateral-CA1 synapses in acute hippocampal slices was significantly depressed; both of these findings indicate a reduction in basal neurotransmission. Studies with specific inhibitors demonstrated that the decrease in basal transmission reflected reduced AMPA receptor-mediated transmission. This was further supported by the observation of reduced numbers of GluR1-immunoreactive puncta in the stratum radiatum. Long-term potentiation (LTP), induced either with.-burst pairing (TBP) or high-frequency stimulation, was impaired in Shank3 heterozygous mice, with no significant change in long-term depression (LTD). In concordance with the LTP results, persistent expansion of spines was observed in control mice after TBP-induced LTP; however, only transient spine expansion was observed in Shank3 heterozygous mice. Male Shank3 heterozygotes displayed less social sniffing and emitted fewer ultrasonic vocalizations during interactions with estrus female mice, as compared to wild-type littermate controls. Conclusions: We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions in Shank3 heterozygous mice. Our results are consistent with altered synaptic development and function in Shank3 haploinsufficiency, highlighting the importance of Shank3 in synaptic function and supporting a link between deficits in synapse function and neurodevelopmental disorders. The reduced glutamatergic transmission that we observed in the Shank3 heterozygous mice represents an interesting therapeutic target in Shank3-haploinsufficiency syndromes. C1 [Bozdagi, Ozlem; Sakurai, Takeshi; Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Bozdagi, Ozlem; Sakurai, Takeshi; Takahashi, Nagahide; Kajiwara, Yuji; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Papapetrou, Danae; Dickstein, Dara L.; Hof, Patrick R.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Wang, Xiaobin; Zhou, Qiang] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Yang, Mu; Katz, Adam M.; Scattoni, Maria Luisa; Harris, Mark J.; Saxena, Roheeni; Silverman, Jill L.; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. [Scattoni, Maria Luisa] Ist Super Sanita, I-00161 Rome, Italy. [Zhou, Qiang] Genentech Inc, San Francisco, CA 94080 USA. RP Buxbaum, JD (reprint author), Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. EM joseph.buxbaum@mssm.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU Seaver Foundation; Simons Foundation; National Institute of Mental Health Intramural Research Program FX This work was supported by the Seaver Foundation, the Simons Foundation, the National Institute of Mental Health Intramural Research Program, and by a gift from Paulina Rychenkova, PhD, and William Gibson. OB and TS are Seaver Junior Faculty Fellows. We thank Lisa Krug and Shekhar Patil for help at early stages of the project. NR 64 TC 180 Z9 186 U1 5 U2 31 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2040-2392 J9 MOL AUTISM JI Mol. Autism PY 2010 VL 1 AR 15 DI 10.1186/2040-2392-1-15 PG 15 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA V30IE UT WOS:000208808900015 PM 21167025 ER PT B AU Grulich, AE Serraino, D Whitby, D AF Grulich, Andrew E. Serraino, Diego Whitby, Denise BE Dittmer, DP Krown, SE TI The Epidemiology of Cancer in People with HIV SO MOLECULAR BASIS FOR THERAPY OF AIDS-DEFINING CANCERS LA English DT Article; Book Chapter ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKINS-LYMPHOMA; SARCOMA-ASSOCIATED HERPESVIRUS; SQUAMOUS-CELL CARCINOMA; AIDS-DEFINING CANCERS; EPSTEIN-BARR-VIRUS; KAPOSIS-SARCOMA; UNITED-STATES; INFECTED PATIENTS AB Three types of cancer, namely Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL), and cervical cancer, are formally designated as AIDS-defining cancers. KS occurs many thousandfold more commonly in people with HIV than in the general population and is causally associated with infection with human herpesvirus-8. Incidence of KS has greatly decreased in recent years in those populations of people with HIV who have access to highly active antiretroviral therapy (HAART). NHL occurs 50- to 100-fold more commonly in people with HIV than in the general population and in a proportion of cases is related to Epstein Barr virus (EBV) infection. Use of HAART has also resulted in substantial declines in incidence of NHL. Cervical cancer occurs up to 20 times more commonly in people with HIV than in the general population, and rates have been little affected by HAART use in recent years. In addition to the AIDS-defining cancers, it has recently become clear that a wider range of mostly viral-associated cancers occur at increased rates in people with HIV. These include Hodgkin's disease, the range of anogenital and oropharyngeal human papillomavirus associated cancers, liver cancer, and conjunctival cancers. Whether or not other cancers including lung cancer - and non-melanoma skin cancer - are associated with HIV infection is the subject of ongoing study. C1 [Grulich, Andrew E.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2010, Australia. [Whitby, Denise] NCI Frederick, Viral Oncol Sect, AIDS & Canc Virus Program, Viral Epidemiol Lab,SAIC Frederick, Frederick, MD 21701 USA. [Serraino, Diego] IRCCS Ctr Riferimento Oncol, I-33081 Aviano, Italy. RP Grulich, AE (reprint author), Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2010, Australia. EM agrulich@nchecr.unsw.edu.au; serrainod@cro.it; whitbyd@ncifcrf.gov NR 109 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1512-2 PY 2010 BP 1 EP 16 DI 10.1007/978-1-4419-1513-9_1 D2 10.1007/978-1-4419-1513-9 PG 16 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA BPI63 UT WOS:000278929600001 ER PT S AU McFarland, HF AF McFarland, Henry F. BE Martin, R Lutterotti, A TI Examination of the Role of MRI in Multiple Sclerosis: A Problem Orientated Approach SO MOLECULAR BASIS OF MULTIPLE SCLEROSIS: THE IMMUNE SYSTEM SE Results and Problems in Cell Differentiation LA English DT Article; Book Chapter ID APPEARING WHITE-MATTER; RESONANCE-IMAGING LESIONS; LONG-TERM DISABILITY; DISEASE-ACTIVITY; CORTICAL DEMYELINATION; GADOLINIUM ENHANCEMENT; DIAGNOSTIC-CRITERIA; PREDICT CONVERSION; CLINICAL-TRIALS; INTERFERON-BETA AB Current multiple sclerosis (MS) is generally thought to consist of two general pathological processes; acute inflammation and degeneration. The relationship between these two components is not understood. What is clear, however, is that the measures of acute inflammation are a poor predictor of long-term disability. Although some have suggested that inflammation may not contribute directly to the essential pathology in MS or that it is secondary to tissue degeneration, most students of the disease believe that the two processes are linked. Therefore, applications of MRI to measure both components of the disease are important. As most readers know, considerable success has been achieved in measuring acute inflammation and very little success has been obtained in identifying measures that correlate with disability and the prediction of future disability has not been achieved. In this review, we will examine the successes and failures of MRI in measuring these two components of the disease process. Consequently, we will not attempt to provide a detailed review of each MRI technique or sequence that has been applied to MS (a number of excellent reviews are available) but rather discuss how these techniques have been applied to answer specific questions. We will provide some comments on the use of MRI in clinical trials as well as in clinical practice. Finally, we will end with a brief discussion of future challenges. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP McFarland, HF (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM mcfarlandh@ninds.nih.gov NR 65 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-1844 BN 978-3-642-14152-2 J9 RESULTS PROBL CELL D JI Results Probl. Cell Differ. PY 2010 VL 51 BP 287 EP 301 DI 10.1007/400_2009_33 D2 10.1007/978-3-642-14153-9 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BQS17 UT WOS:000281691200014 PM 19960380 ER PT B AU Young, LR Gahl, WA AF Young, Lisa R. Gahl, William A. BE McMormack, FX Panos, RJ Trapnell, BC TI Hermansky-Pudlak Syndrome SO MOLECULAR BASIS OF PULMONARY DISEASE: INSIGHTS FROM RARE LUNG DISORDERS SE Respiratory Medicine Series LA English DT Article; Book Chapter DE pulmonary fibrosis; interstitial lung disease; genetic basis of disease; alveolar macrophage; alveolar type II cell ID LYSOSOME-RELATED ORGANELLES; STORAGE-POOL DEFICIENCY; MELANOCYTE-SPECIFIC PROTEINS; VON-WILLEBRAND-FACTOR; AP-3 ADAPTER COMPLEX; PULMONARY-FIBROSIS; OCULOCUTANEOUS ALBINISM; GRANULOMATOUS COLITIS; BETA-3A SUBUNIT; SYNDROME TYPE-5 AB Hermansky Pudlak syndrome (HPS) is a group of rare autosomal recessive disorders characterized by albinism and platelet dysfunction. A subset of HPS patients also develop highly penetrant pulmonary fibrosis, and some patients have a granulomatous colitis that shares features with Crohn's disease. There are at least eight genetic loci associated with HPS in humans; mutations in each HPS gene result in defects in the biogenesis of lysosomes and lysosome-related intracellular organelles including melanosomes, platelet dense granules, and lamellar bodies. Pulmonary disease manifests as a restrictive disorder with insidious dyspnea on exertion, cough, and interstitial infiltrates and can progress to respiratory insufficiency and death by the fourth or fifth decade. Radiographically, HPS lung disease shares many features with idiopathic pulmonary fibrosis (IPF). Pulmonary fibrosis in HPS has a histologic appearance resembling usual interstitial pneumonia in several respects, but is also accompanied by hyperplastic, hypertrophic alveolar type H cells containing enlarged lamellar bodies, and lipid-filled, activated alveolar macrophages. Pigment deficiencies can be quite subtle. All pulmonary fibrosis patients with albinism and a bruising or bleeding diathesis should be screened for HPS. All patients with HPS should be screened for pulmonary involvement with pulmonary function tests and chest imaging. When indicated, bronchoscopy performed by the oral route should be considered to avoid nasal bleeding. Lung biopsy is frequently contraindicated because of bleeding complications and because diagnosis and prognosis can be determined without the procedure. Currently available approaches to treatment of HPS are limited, but include smoking cessation, vaccination against pulmonary infections, and prevention and management of bleeding complications. Pirfenidone and other targeted anti-inflammatory and antifibrotic agents warrant further study. Lung transplantation is an option for HPS patients with advanced pulmonary disease. The Hermansky Pudlak Syndrome Network, Inc. (www.hpsnetwork.org), is a support organization available for patients with HPS. C1 [Young, Lisa R.] Univ Cincinnati, Sch Med, Dept Pediat, Cincinnati, OH 45221 USA. [Young, Lisa R.] Univ Cincinnati, Sch Med, Dept Internal Med, Cincinnati, OH USA. [Young, Lisa R.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Young, LR (reprint author), Univ Cincinnati, Sch Med, Dept Pediat, Cincinnati, OH 45221 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 978-1-58829-963-5 J9 RESPIR MED SER PY 2010 BP 189 EP 207 DI 10.1007/978-1-59745-384-4_8 PG 19 WC Medicine, General & Internal; Respiratory System SC General & Internal Medicine; Respiratory System GA BOF01 UT WOS:000276407000008 ER PT J AU Bernardi, KM Williams, JM Kikkert, M van Voorden, S Wiertz, EJ Ye, YH Tsai, B AF Bernardi, Kaleena M. Williams, Jeffrey M. Kikkert, Marjolein van Voorden, Sjaak Wiertz, Emmanuel J. Ye, Yihong Tsai, Billy TI The E3 Ubiquitin Ligases Hrd1 and gp78 Bind to and Promote Cholera Toxin Retro-Translocation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID RETICULUM-ASSOCIATED DEGRADATION; PROTEIN DISULFIDE-ISOMERASE; ER-ASSOCIATED DEGRADATION; I HEAVY-CHAINS; ENDOPLASMIC-RETICULUM; CYTOSOLIC DEGRADATION; MISFOLDED PROTEINS; CONJUGATING ENZYME; MEMBRANE; DISLOCATION AB To cause disease, cholera toxin (CT) is transported from the cell surface to the endoplasmic reticulum (ER) lumen where the catalytic CTA1 subunit retro-translocates to the cytosol to induce pathological water secretion. Two retro-translocon components are the Derlins and ER-associated multi-spanning E3 ubiquitin ligases including Hrd1 and gp78. We demonstrated previously that Derlin-1 facilitates CTA1 retro-translocation. However, as CTA1 is neither ubiquitinated on lysines nor at its N-terminus, the role of E3 ligases in toxin retro-translocation is unclear. Here, we show that expression of mutant Hrd1 and gp78 and a mutant E2-conjugating enzyme dedicated to retro-translocation (Ube2g2) decrease CTA1 retro-translocation. Hrd1 knockdown also attenuated toxin retro-translocation. Binding studies demonstrate that Hrd1 and gp78 interact with CT and protein disulfide isomerase, an ER chaperone that unfolds CTA1 to initiate translocation. Moreover, we find that the toxin's association with Hrd1 and gp78 is blocked by dominant-negative Derlin-1, suggesting that CT is targeted initially to Derlin-1 and then transferred to Hrd1 and gp78. These data demonstrate a role of the E3 ubiquitin ligases in CTA1 retro-translocation, implicate a sequence of events experienced by the toxin on the ER membrane, and raise the possibility that ubiquitination is involved in the transport process. C1 [Bernardi, Kaleena M.; Williams, Jeffrey M.; Tsai, Billy] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Kikkert, Marjolein; van Voorden, Sjaak; Wiertz, Emmanuel J.] Leiden Univ, Med Ctr, Dept Med Microbiol, Sect Mol Virol, NL-2333 ZA Leiden, Netherlands. [Wiertz, Emmanuel J.] Univ Med Ctr Utrecht, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands. [Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tsai, B (reprint author), Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. EM btsai@umich.edu FU Burroughs Wellcome Fund FX B. T. holds an Investigators in Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. NR 42 TC 41 Z9 42 U1 0 U2 10 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN 1 PY 2010 VL 21 IS 1 BP 140 EP 151 DI 10.1091/mbc.E09-07-0586 PG 12 WC Cell Biology SC Cell Biology GA 539MJ UT WOS:000273258400018 PM 19864457 ER PT J AU Rahimi, Z Muniz, A Parsian, A AF Rahimi, Zohreh Muniz, Adriana Parsian, Abbas TI Detection of responsible mutations for beta thalassemia in the Kermanshah Province of Iran using PCR-based techniques SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE Beta thalassemia; Molecular analysis; Mutation; Western Iran ID MOLECULAR CHARACTERIZATION; SOUTHERN IRAN; SPECTRUM; IDENTIFICATION; PREVENTION; PROGRAM AB Beta Thalassemia has been reported to be a common genetic disorder in Iran. To establish the molecular spectrum of the beta thalassemias in the Kermanshah Province of Iran, 185 unrelated beta thalassemia patients with Kurdish ethnic background were studied (181 beta-thalassemia major and 4 beta-thalassemia intermedia). Using polymerase chain reaction-amplification refractory mutation system (PCR-ARMS), restriction fragment length polymorphism (RFLP) and direct genomic sequencing twenty different mutations were identified accounting for 98.1% of the alleles. Approximately 80.8% of beta-thalassemia chromosomes had beta(0) mutation. The most prevalent mutation was the IVSII-1 (G -> A) (32.97%), followed by CD8/9 +G (13.51%), IVSI-110 (C -> T) (8.38%), CD 36/37 -T (7.84%), CD8 -AA (5.94%), CD15 (G -> A) (4.86%) and IVSI-1 (G -> A) (4.59%). All of these mutations accounted for 78.1% of the alleles. The results described here will be of valuable help in the development of successful prevention programs for the population of Kermanshah. C1 [Rahimi, Zohreh] Kermanshah Univ Med Sci, Sch Med, Med Biol Res Ctr, Kermanshah, Iran. [Rahimi, Zohreh] Kermanshah Univ Med Sci, Sch Med, Dept Biochem, Kermanshah, Iran. [Muniz, Adriana] Albert Einstein Coll Med, Dept Physiol & Biophys, Div Hematol, Dept Med, Bronx, NY 10467 USA. [Parsian, Abbas] NIH, Div Neurosci & Behav, Rockville, MD USA. RP Rahimi, Z (reprint author), Kermanshah Univ Med Sci, Sch Med, Med Biol Res Ctr, POB 67148-69914,Daneshgah Ave, Kermanshah, Iran. EM zrahimi@kums.ac.ir OI Rahimi, Zohreh/0000-0001-7589-3307 NR 27 TC 20 Z9 22 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-4851 J9 MOL BIOL REP JI Mol. Biol. Rep. PD JAN PY 2010 VL 37 IS 1 BP 149 EP 154 DI 10.1007/s11033-009-9560-0 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 540GI UT WOS:000273319000022 PM 19437135 ER PT J AU Venancio, TM Balaji, S Aravind, L AF Venancio, Thiago M. Balaji, S. Aravind, L. TI High-confidence mapping of chemical compounds and protein complexes reveals novel aspects of chemical stress response in yeast SO MOLECULAR BIOSYSTEMS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; BIOACTIVE COMPOUNDS; GENOME; ACTIN; TRAFFICKING; EXPRESSION; NETWORKS; DYNAMICS; UPDATE; TARGET AB Chemical genetics in yeast has shown great potential for clarifying the pharmacology of various drugs. Investigating these results from a systems perspective has uncovered many facets of natural chemical tolerance, but many cellular interactions of chemicals still remain poorly understood. To uncover previously overlooked players in resistance to chemical stress we integrated several independent chemical genetics datasets with protein-protein interactions and a comprehensive collection of yeast protein complexes. As a consequence we were able to identify the potential targets and mode of action of certain poorly understood compounds. However, most complexes recovered in our analysis appear to perform indirect roles in countering deleterious effects of chemicals by constituting an underlying intricate buffering system that has been so far under-appreciated. This buffering role appears to be largely contributed to by complexes pertaining to chromatin and vesicular dynamics. The former set of complexes seems to act by setting up or maintaining gene expression states necessary to protect the cell against chemical effects. Among the latter complexes we found an important role for specific vesicle tethering complexes in tolerating particular sets of compounds, indicating that different chemicals might be routed via different points in the intracellular trafficking system. We also suggest a general operational similarity between these complexes and molecular capacitors (e. g. the chaperone Hsp90). Both have a key role in increasing the system's robustness, although at different levels, through buffering stress and mutation, respectively. It is therefore conceivable that some of these complexes identified here might have roles in molding the evolution of chemical resistance and response. C1 [Venancio, Thiago M.; Balaji, S.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Balaji, S.] Harvard Univ, Ctr Canc Syst Biol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Venancio, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM venancit@ncbi.nlm.nih.gov; aravind@ncbi.nlm.nih.gov RI Venancio, Thiago/B-5003-2011; Entomologiamolecular, Inct/J-8214-2013 FU National Institutes of Health, USA FX We acknowledge the Intramural Research Program of the National Institutes of Health, USA, for funding our research. Due to space constraints we apologize for not citing all the manuscripts from which we extracted data but provide them in the ESI (Additional file 1). NR 43 TC 10 Z9 11 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 1 BP 175 EP 181 DI 10.1039/b911821g PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 534DH UT WOS:000272875200020 PM 20024079 ER PT J AU Sakurai, M Rose, NR Schultz, L Quinn, AM Jadhav, A Ng, SS Oppermann, U Schofield, CJ Simeonov, A AF Sakurai, Masaaki Rose, Nathan R. Schultz, Lena Quinn, Amy M. Jadhav, Ajit Ng, Stanley S. Oppermann, Udo Schofield, Christopher J. Simeonov, Anton TI A miniaturized screen for inhibitors of Jumonji histone demethylases SO MOLECULAR BIOSYSTEMS LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR; 2-OXOGLUTARATE OXYGENASES; IDENTIFICATION; HIF-1-ALPHA; ACTIVATION; IRON; METHYLTRANSFERASE; ACCUMULATION; HYDROXYLASES; FLAVONOIDS AB 2-Oxoglutarate-and Fe(II)-dependent oxygenases are a major class of Ne-methyl lysine demethylases that are involved in epigenetic regulation. Assays suitable for implementation in a high-throughput manner have been lacking for these enzymes. Here, we describe the design and implementation of a robust and miniaturized high-throughput kinetic assay for inhibitors of JMJD2E using a formaldehyde dehydrogenase-coupled reaction with real-time fluorescence detection. Reactant compatibility studies resulted in simplification of the assay scheme to the mixing of two reagent solutions, both of which were stable overnight. The assay was miniaturized to a 4 mu L volume in 1536-well format and was used to screen the library of pharmacologically active compounds (LOPAC 1280). Inhibitors identified by the screen were further characterized in secondary assays including FDH counterscreen and demethylation assays that monitored demethylation by MALDI-TOF MS. The assay developed here will enable the screening of large compound libraries against the Jumonji demethylases in a robust and automated fashion. C1 [Rose, Nathan R.; Schofield, Christopher J.] Univ Oxford, Dept Chem, Oxford OX1 3TA, England. [Rose, Nathan R.; Schofield, Christopher J.] Univ Oxford, Oxford Ctr Integrat Syst Biol, Oxford OX1 3TA, England. [Sakurai, Masaaki; Schultz, Lena; Quinn, Amy M.; Jadhav, Ajit; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. [Ng, Stanley S.; Oppermann, Udo] Univ Oxford, Struct Genom Consortium, Headington OX3 7DQ, England. [Ng, Stanley S.; Oppermann, Udo] Botnar Res Ctr, Oxford Biomed Res Unit, Oxford OX3 7LD, England. RP Schofield, CJ (reprint author), Univ Oxford, Dept Chem, S Parks Rd, Oxford OX1 3TA, England. EM christopher.schofield@chem.ox.ac.uk; asimeono@mai.nih.gov RI Rose, Nathan/A-9270-2013; Socaciu, Carmen/P-8358-2014; OI Rose, Nathan/0000-0002-1871-1156; Socaciu, Carmen/0000-0002-7352-5057; Schofield, Christopher/0000-0002-0290-6565 FU NIH Roadmap for Medical Research; NHGRI, NIH; Wellcome Trust; Biotechnology and Biological Sciences Research Council; Commonwealth Scholarship Commission in the United Kingdom; Oxford NIHR Biomedical Research Unit; Canadian Institutes for Health Research [1097737]; Canadian Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut; Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation, Merck Co., Inc; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research FX This research was supported in part by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research and the Intramural Research Program of the NHGRI, NIH, and in part by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council and the Commonwealth Scholarship Commission in the United Kingdom and by the Oxford NIHR Biomedical Research Unit. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research and the Wellcome Trust. NR 41 TC 44 Z9 44 U1 0 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 2 BP 357 EP 364 DI 10.1039/b912993f PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 546CS UT WOS:000273786600009 PM 20094655 ER PT J AU Yasgar, A Foley, TL Jadhav, A Inglese, J Burkart, MD Simeonov, A AF Yasgar, Adam Foley, Timothy L. Jadhav, Ajit Inglese, James Burkart, Michael D. Simeonov, Anton TI A strategy to discover inhibitors of Bacillus subtilis surfactin-type phosphopantetheinyl transferase SO MOLECULAR BIOSYSTEMS LA English DT Article ID CARRIER PROTEIN SYNTHASE; THROUGHPUT SCREENING ASSAYS; ALLOSTERIC MODULATOR; IDENTIFICATION; BIOSYNTHESIS; LIBRARIES; RECEPTOR; MYCOBACTERIA; SCH-202676; BINDING AB Surfactin-type phosphopantetheinyl transferases (Sfp-PPTases) are responsible for modifying type I polyketide and non-ribosomal peptide synthases of prokaryotes and have been implicated in the activation of a variety of pathogen-associated virulence factors. As such, inhibitors of this enzyme class represent enticing leads for antibiotic development and can serve as tools in studies of bacterial metabolism. Currently, no small molecule inhibitors of Sfp-PPTase are known, highlighting the need for efficient methods for PPTase inhibitor identification and development. Herein, we present the design and implementation of a robust and miniaturized high-throughput kinetic assay for inhibitors of Sfp-PPTase using the substrate combination of rhodamine-labeled coenzyme A and Black Hole Quencher-2 labeled consensus acceptor peptide YbbR. Upon PPTase-catalyzed transfer of the rhodamine-labeled phosphopantetheinyl arm onto the acceptor peptide, the fluorescent donor and quencher are covalently joined and the fluorescence signal is reduced. This assay was miniaturized to a low 4 mu L volume in 1536-well format and was used to screen the library of pharmacologically active compounds (LOPAC(1280)). Top inhibitors identified by the screen were further characterized in secondary assays, including protein phosphopantetheinylation detected by gel electrophoresis. The present assay enables the screening of large compound libraries against Sfp-PPTase in a robust and automated fashion and is applicable to designing assays for related transferase enzymes. C1 [Foley, Timothy L.; Burkart, Michael D.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Yasgar, Adam; Jadhav, Ajit; Inglese, James; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Burkart, MD (reprint author), Univ Calif San Diego, Dept Chem & Biochem, San Diego 9500 Gilman Dr, La Jolla, CA 92093 USA. EM mburkart@ucsd.edu; asimeono@mail.nih.gov FU NIH Roadmap for Medical Research; NHGRI, NIH [1R03MH083266] FX This research was supported in part by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research, the Intramural Research Program of the NHGRI, NIH, and grant 1R03MH083266 (M.D.B.). NR 37 TC 21 Z9 21 U1 0 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 2 BP 365 EP 375 DI 10.1039/b913291k PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 546CS UT WOS:000273786600010 PM 20094656 ER PT J AU Watrous, J Burns, K Liu, WT Patel, A Hook, V Bafna, V Barry, CE Bark, S Dorrestein, PC AF Watrous, Jeramie Burns, Kristin Liu, Wei-Ting Patel, Anand Hook, Vivian Bafna, Vineet Barry, Clifton E., III Bark, Steve Dorrestein, Pieter C. TI Expansion of the mycobacterial "PUPylome'' SO MOLECULAR BIOSYSTEMS LA English DT Article ID UBIQUITIN-LIKE PROTEIN; TANDEM MASS-SPECTRA; ANTIOXIDANT DEFENSE; NITRIC-OXIDE; TUBERCULOSIS; PROTEASOME; ENZYMES; IDENTIFICATION; DEGRADATION; INHIBITION AB Selective degradation of cellular proteins offers an important mechanism to coordinate cellular processes including cell differentiation, defense, metabolic control, signal transduction and proliferation. While much is known about eukaryotic ubiquitination, we know little about the recently discovered ubiquitin-like protein in prokaryotes (PUP). Through expression of His(7) tagged PUP and exploitation of the characteristic + 243 Da mass shift attributed to trypsinized PUPylated peptides, a global pull-down of protein targets for PUPylation in Mycobacterium smegmatis revealed 103 candidate PUPylation targets and 52 confirmed targets. Similar to eukaryotic ubiquitination, further analysis of these targets revealed neither primary sequence nor secondary structure homology at the point of attachment. Pathways containing PUPylated proteins include many central to rapid cell growth, such as glycolysis, gluconeogenesis, amino acid and mycolic acid metabolism and biosynthesis, as well as translation. Seventeen of the 29 nitrosylated protein targets previously identified in Mycobacterium tuberculosis were also identified as PUPylation candidates indicating a connection between PUP-mediated remodeling of critical metabolic pathways and the mycobacterial response to exogenous stress. C1 [Watrous, Jeramie; Liu, Wei-Ting; Dorrestein, Pieter C.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Burns, Kristin; Barry, Clifton E., III] NIAID, TB Res Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Patel, Anand; Bafna, Vineet] Univ Calif San Diego, Dept Comp Sci, La Jolla, CA 92093 USA. [Hook, Vivian; Bark, Steve; Dorrestein, Pieter C.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Dorrestein, Pieter C.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. RP Dorrestein, PC (reprint author), Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Ave,BSB 4090,MC 0636, La Jolla, CA 92093 USA. EM pdorrestein@ucsd.edu RI Dorrestein, Pieter/D-5012-2012; Barry, III, Clifton/H-3839-2012 FU Intramural Research Division of the NIAID; Skaggs School of Pharmacy and Pharmaceutical Sciences; NIH Molecular Biophysics Training Program [GM08326]; NIH [P01 HL58120, R01 DA04271, 5K01DA23065]; NIDA FX This work was supported (in part) by the Intramural Research Division of the NIAID, the Skaggs School of Pharmacy and Pharmaceutical Sciences (P.D.), the NIH Molecular Biophysics Training Program GM08326 (J.W.), NIH Grant P01 HL58120 (V.H.), NIH Grant R01 DA04271 (V.H.), and NIDA and NIH Grant 5K01DA23065 (S.B.). NR 29 TC 43 Z9 99 U1 0 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X EI 1742-2051 J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 2 BP 376 EP 385 DI 10.1039/b916104j PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 546CS UT WOS:000273786600011 PM 20094657 ER PT J AU Galperin, MY Higdon, R Kolker, E AF Galperin, Michael Y. Higdon, Roger Kolker, Eugene TI Interplay of heritage and habitat in the distribution of bacterial signal transduction systems SO MOLECULAR BIOSYSTEMS LA English DT Article ID MYCOBACTERIUM-VANBAALENII PYR-1; CONSERVED HYPOTHETICAL PROTEINS; COMPLETE GENOME SEQUENCE; RESPONSE REGULATORS; BIOFILM FORMATION; VARIABLE SHELL; SIGMA FACTORS; STABLE CORE; DI-GMP; EVOLUTION AB Comparative analysis of the complete genome sequences from a variety of poorly studied organisms aims at predicting ecological and behavioral properties of these organisms and helping in characterizing their habitats. This task requires finding appropriate descriptors that could be correlated with the core traits of each system and would allow meaningful comparisons. Using the relatively simple bacterial models, first attempts have been made to introduce suitable metrics to describe the complexity of organism's signaling machinery, which included introducing the "bacterial IQ'' score. Here, we use an updated census of prokaryotic signal transduction systems to improve this parameter and evaluate its consistency within selected bacterial phyla. We also introduce a more elaborate descriptor, a set of profiles of relative abundance of members of each family of signal transduction proteins encoded in each genome. We show that these family profiles are well conserved within each genus and are often consistent within families of bacteria. Thus, they reflect evolutionary relationships between organisms as well as individual adaptations of each organism to its specific ecological niche. C1 [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Higdon, Roger; Kolker, Eugene] Seattle Childrens Res Inst, Bioinformat & High Throughput Anal Lab, Seattle, WA 98101 USA. [Higdon, Roger; Kolker, Eugene] Seattle Childrens Hosp, Seattle, WA 98105 USA. [Kolker, Eugene] Univ Washington, Biomed & Hlth Informat Div, Med Educ & Biomed Hlth Dept, Sch Med, Seattle, WA 98105 USA. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Kolker, Eugene/C-6711-2008; Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU National Library of Medicine (MYG); NIGMS [R01 GM076680-02]; NIDDK [UO1 DK072473]; NSF [DBI-0544757, NSF-07140] FX This work was supported by the NIH Intramural Research Program at the National Library of Medicine (MYG) and by grants to EK from the NIGMS (R01 GM076680-02), NIDDK (UO1 DK072473), and the NSF (DBI-0544757 and NSF-07140). NR 56 TC 51 Z9 51 U1 0 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 4 BP 721 EP 728 DI 10.1039/b908047c PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 570YP UT WOS:000275715000013 PM 20237650 ER PT J AU Venancio, TM Balaji, S Geetha, S Aravind, L AF Venancio, Thiago M. Balaji, S. Geetha, S. Aravind, L. TI Robustness and evolvability in natural chemical resistance: identification of novel systems properties, biochemical mechanisms and regulatory interactions SO MOLECULAR BIOSYSTEMS LA English DT Article ID GENOME-WIDE SCREEN; SACCHAROMYCES-CEREVISIAE GENOME; YEAST DELETION MUTANTS; DOMAIN PROTEINS SLM1; DNA-DAMAGING AGENTS; VACUOLAR H+-ATPASE; GENE-EXPRESSION; FUNCTIONAL-ORGANIZATION; TRYPTOPHAN PERMEASE; BIOACTIVE COMPOUNDS AB A vast amount of data on the natural resistance of Saccharomyces cerevisiae to a diverse array of chemicals has been generated over the past decade (chemical genetics). We endeavored to use this data to better characterize the "systems" level properties of this phenomenon. By collating data from over 30 different genome-scale studies on growth of gene deletion mutants in presence of diverse chemicals, we assembled the largest currently available gene-chemical network. We also derived a second gene-gene network that links genes with significantly overlapping chemical-genetic profiles. We analyzed properties of these networks and investigated their significance by overlaying various sources of information, such as presence of TATA boxes in their promoters (which typically correlate with transcriptional noise), association with TFIID or SAGA, and propensity to function as phenotypic capacitors. We further combined these networks with ubiquitin and protein kinase-substrate networks to understand chemical tolerance in the context of major post-translational regulatory processes. Hubs in the gene-chemical network (multidrug resistance genes) are notably enriched for phenotypic capacitors (buffers against phenotypic variation), suggesting the generality of these players in buffering mechanistically unrelated deleterious forces impinging on the cell. More strikingly, analysis of the gene-gene network derived from the gene-chemical network uncovered another set of genes that appear to function in providing chemical tolerance in a cooperative manner. These appear to be enriched in lineage-specific and rapidly diverging members that also show a corresponding tendency for SAGA-dependent regulation, evolutionary divergence and noisy expression patterns. This set represents a previously underappreciated component of the chemical response that enables cells to explore alternative survival strategies. Thus, systems robustness and evolvability are simultaneously active as general forces in tolerating environmental variation. We also recover the actual genes involved in the above-discussed network properties and predict the biochemistry of their products. Certain key components of the ubiquitin system (e. g. Rcy1, Wss1 and Ubp16), peroxisome recycling (e. g. Irs4) and phosphorylation cascades (e. g. NPR1, MCK1 and HOG) are major participants and regulators of chemical resistance. We also show that a major sub-network boosting mitochondrial protein synthesis is important for exploration of alternative survival strategies under chemical stress. Further, we find evidence that cellular exploration of survival strategies under chemical stress and secondary metabolism draw from a common pool of biochemical players (e. g. acetyltransferases and a novel NTN hydrolase). C1 [Venancio, Thiago M.; Balaji, S.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Balaji, S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Geetha, S.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Venancio, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM thiago.venancio@gmail.com; balaji.ncbi@gmail.com; hemeetha@gmail.com; aravind@mail.nih.gov RI Venancio, Thiago/B-5003-2011; Entomologiamolecular, Inct/J-8214-2013 FU National Institutes of Health, USA FX We acknowledge the Intramural Research Program of the National Institutes of Health, USA for funding our research. We also would like to acknowledge all the authors who have made their genome-scale datasets publicly available. We tried to make the most extensive collection possible and express our regret if we accidentally missed some study in the data gathering process. NR 131 TC 9 Z9 11 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 8 BP 1475 EP 1491 DI 10.1039/c002567b PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 625SC UT WOS:000279914300019 PM 20517567 ER PT J AU Zhang, YL Campbell, C Li, QA Gildersleeve, JC AF Zhang, Yalong Campbell, Christopher Li, Qian Gildersleeve, Jeffrey C. TI Multidimensional glycan arrays for enhanced antibody profiling SO MOLECULAR BIOSYSTEMS LA English DT Article ID INDEPENDENT PROSTATE-CANCER; CARBOHYDRATE MICROARRAYS; ANTIGEN-EXPRESSION; SERUM ANTIBODIES; VACCINE; PROTEIN; COMBINATION; RESPONSES; BINDING; IMMUNOTHERAPY AB Carbohydrate-binding antibodies play a critical role in basic and clinical research. Monoclonal antibodies that bind glycans are used to measure carbohydrate expression, and serum antibodies to glycans can be important elements of the immune response to pathogens and vaccines. Carbohydrate antigen arrays, or glycan arrays, have emerged as powerful tools for the high-throughput analysis of carbohydrate-protein interactions. Our group has focused on the development and application of neoglycoprotein arrays, a unique array format wherein carbohydrates are covalently attached to a carrier protein prior to immobilization on the surface. The neoglycoprotein format permits variations of glycan structure, glycan density, and neoglycoprotein density on a single array. The focus of this study was on the effects of neoglycoprotein density on antibody binding. First, we evaluated binding of five monoclonal antibodies (81FR2.2, HE-195, HE-193, B480, and Z2A) to the blood group A antigen and found that neoglycoprotein density had a substantial effect on recognition. Next, we profiled serum antibodies in 15 healthy individuals and showed that inclusion of multiple neoglycoprotein densities helps distinguish different subpopulations of antibodies. Finally, we evaluated immune responses induced by a prostate cancer vaccine and showed that variations in neoglycoprotein density enable one to detect antibody responses that could not be detected otherwise. Neoglycoprotein density is a useful element of diversity for evaluating antibody recognition and, when combined with variations in glycan structure and glycan density, provides multidimensional glycan arrays with enhanced performance for monoclonal antibody development, biomarker discovery, and vaccine optimization. C1 [Zhang, Yalong; Campbell, Christopher; Li, Qian; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, 376 Boyles St,Bldg 376, Frederick, MD 21702 USA. EM gildersj@mail.nih.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU NIH, NCI; NIGMS FX We thank Dr Jeffrey Schlom and Dr James Gulley for the generous gift of serum samples. This research was supported by the Intramural Research Program of the NIH, NCI, and by the NIGMS through a Pharmacology Research Associate Training (PRAT) fellowship (CTC). NR 46 TC 15 Z9 15 U1 1 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 9 BP 1583 EP 1591 DI 10.1039/c002259d PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 638CG UT WOS:000280868000012 PM 20711537 ER PT J AU Fong, JH Panchenko, AR AF Fong, Jessica H. Panchenko, Anna R. TI Intrinsic disorder and protein multibinding in domain, terminal, and linker regions SO MOLECULAR BIOSYSTEMS LA English DT Article ID MOLECULAR RECOGNITION FEATURES; INTERACTION NETWORKS; UNSTRUCTURED PROTEINS; FUNCTION PARADIGM; HUB PROTEINS; BINDING; EVOLUTION; PREDICTION; MECHANISM; DATABASE AB Intrinsic disorder is believed to contribute to the ability of some proteins to interact with multiple partners which is important for protein functional promiscuity and regulation of the cross-talk between pathways. To better understand the mechanisms of molecular recognition through disordered regions, here, we systematically investigate the coupling between disorder and binding within domain families in a structure interaction network and in terminal and inter-domain linker regions. We showed that the canonical domain-domain interaction model should take into account contributions of N- and C-termini and inter-domain linkers, which may form all or part of the binding interfaces. For the majority of proteins, binding interfaces on domain and terminal regions were predicted to be less disordered than non-interface regions. Analysis of all domain families revealed several exceptions, such as kinases, DNA/RNA binding proteins, certain enzymes, and regulatory proteins, which are candidates for disorder-to-order transitions that can occur upon binding. Domain interfaces that bind single or multiple partners do not exhibit significant difference in disorder content if normalized by the number of interactions. In general, protein families with more diverse interactions exhibit less average disorder over all members of the family. Our results shed light on recent controversies regarding the relationship between disorder and binding of multiple partners at common interfaces. In particular, they support the hypothesis that protein domains with many interacting partners should have a pleiotropic effect on functional pathways and consequently might be more constrained in evolution. C1 [Fong, Jessica H.; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Fong, JH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM fongj@ncbi.nlm.nih.gov; panch@ncbi.nlm.nih.gov FU NIH, National Library of Medicine FX We thank Vladimir Uversky for insightful discussions. This research was supported by the Intramural Research Program of the NIH, National Library of Medicine. NR 65 TC 9 Z9 9 U1 0 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 10 BP 1821 EP 1828 DI 10.1039/c005144f PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649LR UT WOS:000281772300013 PM 20544079 ER PT J AU Urzua, U Best, L Munroe, DJ AF Urzua, Ulises Best, Lionel Munroe, David J. TI Microarray proteomic analysis discriminates tumorigenic mouse ovarian surface epithelial cells of divergent aggressive potential SO MOLECULAR BIOSYSTEMS LA English DT Article ID BREAST-CANCER; IN-VITRO; CLINICAL-IMPLICATIONS; GENE-EXPRESSION; MURINE MODEL; GROWTH; RISK; DIFFERENTIATION; IDENTIFICATION; PATHOGENESIS AB Cancer is an intrinsically heterogeneous disease. Tumors classified under the same etiology and histological type may display divergent growth and invasion properties, resulting in different progression rates and clinical outcomes. Here, we approached this subject in a syngeneic mouse model of ovarian cancer. Antibody microarrays were applied to obtain the proteomic profiles of IF5 and IG10, two spontaneously transformed mouse ovarian surface epithelial (MOSE) cell lines of cognate clonal origin but different tumorigenic behavior in vivo. Repeated dye-swap allowed filter out about 40% of inconsistent signals from a total of 224 arrayed antibodies. Two-class comparison tests resulted in 31 differentially expressed proteins (adjusted p < 0.05). Proteins of the ErbB and focal adhesion signaling pathways showed higher levels in IG10, the most aggressive cell. In contrast, the less aggressive IF5 cell was enriched in proteins related to nuclear chromatin organization and cell-cycle. Additionally, comparison between protein levels and mRNA levels of MOSE cells resulted in a positive rank correlation for 50-60% of protein-mRNA pairs (p < 1.7 x 10 (5)). Importantly, the protein profile of IG10 is linked to invasion and chemotherapy response in human ovarian tumors while the IF5 profile is associated to growth control. The minimal IG10 network contained the proteins Jun, Smad4, Myc, Atf2, and Pak1 as major nodes while Chek2, Mdm2 and Ccna2 were the predominant nodes of the IF5 network. The molecular basis accounting for a high aggressive potential not necessarily related to an increased tumor growth capacity is discussed on a pathway-network basis. C1 [Urzua, Ulises] Univ Chile, ICBM Fac Med, Lab Genom Aplicada, Santiago, Chile. [Best, Lionel; Munroe, David J.] NCI, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Urzua, U (reprint author), Univ Chile, ICBM Fac Med, Lab Genom Aplicada, Independencia 1027, Santiago, Chile. EM uurzua@med.uchile.cl RI Urzua, Ulises/A-3982-2013; OI Urzua, Ulises/0000-0003-0522-5754 FU ORFD Program-OIA; National Cancer Institute (NCI) at NIH; NCI [N01-C0-12400]; VID, Universidad de Chile [I205/09-2]; Mecesup [UCH0115] FX UU was supported by the ORFD Program-OIA, National Cancer Institute (NCI) at NIH. This work was partially supported with NCI's funds under contract N01-C0-12400. Bioinformatic work has been supported by grant I205/09-2 (UU) from VID, Universidad de Chile. The pilot Microarray facility at ICBM, Facultad de Medicina, Universidad de Chile, has been funded by the Mecesup UCH0115 grant. NR 38 TC 1 Z9 1 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2010 VL 6 IS 12 BP 2521 EP 2528 DI 10.1039/c005220e PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 676SD UT WOS:000283937800020 PM 20938528 ER PT J AU Gu, XL Long, CX Sun, LX Xie, CS Lin, X Cai, HB AF Gu, Xing-Long Long, Cai-Xia Sun, Lixin Xie, Chengsong Lin, Xian Cai, Huaibin TI Astrocytic expression of Parkinson's disease-related A53T alpha-synuclein causes neurodegeneration in mice SO MOLECULAR BRAIN LA English DT Article AB Background: Parkinson's disease (PD) is the most common movement disorder. While neuronal deposition of alpha-synuclein serves as a pathological hallmark of PD and Dementia with Lewy Bodies, alpha-synuclein-positive protein aggregates are also present in astrocytes. The pathological consequence of astrocytic accumulation of alpha-synuclein, however, is unclear. Results: Here we show that PD-related A53T mutant alpha-synuclein, when selectively expressed in astrocytes, induced rapidly progressed paralysis in mice. Increasing accumulation of alpha-synuclein aggregates was found in presymptomatic and symptomatic mouse brains and correlated with the expansion of reactive astrogliosis. The normal function of astrocytes was compromised as evidenced by cerebral microhemorrhage and down-regulation of astrocytic glutamate transporters, which also led to increased inflammatory responses and microglial activation. Interestingly, the activation of microglia was mainly detected in the midbrain, brainstem and spinal cord, where a significant loss of dopaminergic and motor neurons was observed. Consistent with the activation of microglia, the expression level of cyclooxygenase 1 (COX-1) was significantly up-regulated in the brain of symptomatic mice and in cultured microglia treated with conditioned medium derived from astrocytes over-expressing A53T alpha-synuclein. Consequently, the suppression of COX-1 activities extended the survival of mutant mice, suggesting that excess inflammatory responses elicited by reactive astrocytes may contribute to the degeneration of neurons. Conclusions: Our findings demonstrate a critical involvement of astrocytic alpha-synuclein in initiating the non-cell autonomous killing of neurons, suggesting the viability of reactive astrocytes and microglia as potential therapeutic targets for PD and other neurodegenerative diseases. C1 [Gu, Xing-Long; Long, Cai-Xia; Sun, Lixin; Xie, Chengsong; Lin, Xian; Cai, Huaibin] NIA, Units Transgenesis, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cai, HB (reprint author), NIA, Units Transgenesis, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI gu, xinglong/A-3054-2011; Cai, Huaibin/H-3359-2013 OI gu, xinglong/0000-0002-0437-5606; Cai, Huaibin/0000-0002-8596-6108 FU National Institute on Aging at the National Institutes of Health [Z01-AG000959-05] FX This work was supported by the intramural research programs of National Institute on Aging at the National Institutes of Health (H.C., Z01-AG000959-05). We thank Dr. Xiao-Jiang Li for helpful suggestions. We thank the NIH Fellows Editorial Board for manuscript editing. NR 56 TC 51 Z9 53 U1 3 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-6606 J9 MOL BRAIN JI Mol. Brain PY 2010 VL 3 AR 12 DI 10.1186/1756-6606-3-12 PG 16 WC Neurosciences SC Neurosciences & Neurology GA V25CX UT WOS:000208457200012 PM 20409326 ER PT J AU Romero-Weaver, AL Wang, HW Steen, HC Scarzello, AJ Hall, VL Sheikh, F Donnelly, RP Gamero, AM AF Romero-Weaver, Ana L. Wang, Hsiang-Wen Steen, Hakan C. Scarzello, Anthony J. Hall, Veronica L. Sheikh, Faruk Donnelly, Raymond P. Gamero, Ana M. TI Resistance to IFN-alpha-Induced Apoptosis Is Linked to a Loss of STAT2 SO MOLECULAR CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; INTERFERON-ALPHA; MELANOMA-CELLS; SIGNALING PATHWAY; TYROSINE PHOSPHORYLATION; MAMMALIAN TARGET; CLASS-I; ACTIVATION; EXPRESSION; INDUCTION AB Type I IFNs (IFN-alpha/beta) are pleitropic cytokines widely used in the treatment of certain malignancies, hepatitis B and C, and multiple sclerosis. IFN resistance is a challenging clinical problem to overcome. Hence, understanding the molecular mechanism by which IFN immunotherapy ceases to be effective is of translational importance. In this study, we report that continuous IFN-alpha stimulation of the human Jurkat variant H123 led to resistance to type I IFN-induced apoptosis due to a loss of signal transducers and activators of transcription 2 (STAT2) expression. The apoptotic effects of IFN-alpha were hampered as STAT2-deficient cells were defective in activating the mitochondrial-dependent death pathway and ISGF3-mediated gene activation. Reconstitution of STAT2 restored the apoptotic effects of IFN-alpha as measured by the loss of mitochondrial membrane potential, cytochrome c release from mitochondria, caspase activation, and ultimately cell death. Nuclear localization of STAT2 was a critical event as retention of tyrosine-phosphorylated STAT2 in the cytosol was not sufficient to activate apoptosis. Furthermore, silencing STAT2 gene expression in Saos2 and A375S.2 tumor cell lines significantly reduced the apoptotic capacity of IFN-alpha. Altogether, we show that STAT2 is a critical mediator in the activation of type I IFN-induced apoptosis. More importantly, defects in the expression or nuclear localization of STAT2 could lessen the efficacy of type I IFN immunotherapy. Mol Cancer Res; 8(1); 80-92. (C) 2010 AACR. C1 [Romero-Weaver, Ana L.; Wang, Hsiang-Wen; Scarzello, Anthony J.; Hall, Veronica L.; Gamero, Ana M.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. [Steen, Hakan C.; Gamero, Ana M.] Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19122 USA. [Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Gamero, AM (reprint author), 3440 N Broad St,Kresge Hall,Room 622, Philadelphia, PA 19041 USA. EM gameroa@temple.edu FU National Cancer Institute, NIH [N01-CO-12400]; National Cancer Institute [K22CA095326]; NIH, National Cancer Institute, Center for Cancer Research FX Whole or in part with Federal funds from the National Cancer Institute, NIH under contract no. N01-CO-12400 (A. M. Gamero, A. L. Romero-Weaver, H-W. Wang). This project described was also supported by award no. K22CA095326 from the National Cancer Institute (A. M. Gamero). This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 45 TC 17 Z9 17 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2010 VL 8 IS 1 BP 80 EP 92 DI 10.1158/1541-7786.MCR-08-0344 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 606EK UT WOS:000278404700008 PM 20068068 ER PT J AU Reinhold, WC Reimers, MA Lorenzi, P Ho, J Shankavaram, UT Ziegler, MS Bussey, KJ Nishizuka, S Ikediobi, O Pommier, YG Weinstein, JN AF Reinhold, William C. Reimers, Mark A. Lorenzi, Philip Ho, Jennifer Shankavaram, Uma T. Ziegler, Micah S. Bussey, Kimberly J. Nishizuka, Satoshi Ikediobi, Ogechi Pommier, Yves G. Weinstein, John N. TI Multifactorial Regulation of E-Cadherin Expression: An Integrative Study SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CANCER-CELL-LINES; INVASION-SUPPRESSOR GENE; REPRESSES E-CADHERIN; BREAST-CANCER; DNA METHYLATION; PROSTATE-CANCER; MESENCHYMAL TRANSITIONS; MOLECULAR PHARMACOLOGY; MALIGNANT PROGRESSION; MELANOMA PROGRESSION AB E-cadherin (E-cad) is an adhesion molecule associated with tumor invasion and metastasis. Its down-regulation is associated with poor prognosis for many epithelial tumor types. We have profiled E-cad in the NCI-60 cancer cell lines at the DNA, RNA, and protein levels using six different microarray platforms plus bisulfite sequencing. Here we consider the effects on E-cad expression of eight potential regulatory factors: E-cad promoter DNA methylation, the transcript levels of six transcriptional repressors (SNAI1, SNAI2, TCF3, TCF8, TWIST1, and ZFHX1B), and E-cad DNA copy number. Combined bioinformatic and pharmacological analyses indicate the following ranking of influence on E-cad expression: (1) E-cad promoter methylation appears predominant, is strongly correlated with E-cad expression, and shows a 20% to 30% threshold above which E-cad expression is silenced; (2) TCF8 expression levels correlate with (-0.62) and predict (P < 0.00001) E-cad expression; (3) SNAI2 and ZFHX1B expression levels correlate positively with each other (+0.83) and also correlate with (-0.32 and -0.30, respectively) and predict (P = 0.03 and 0.01, respectively) E-cad expression; (4) TWIST1 correlates with (-0.34) but does not predict E-cad expression; and (5) SNAI1 expression, TCF3 expression, and E-cad DNA copy number do not correlate with or predict E-cad expression. Predictions of E-cad regulation based on the above factors were tested and verified by demethylation studies using 5-aza-2'-deoxycytidine treatment; siRNA knock-down of TCF8, SNAI2, or ZFHX1B expression; and combined treatment with 5-aza-2'-deoxycytidine and TCF8 siRNA. Finally, levels of cellular E-cad expression are associated with levels of cell-cell adhesion and response to drug treatment. Mol Cancer Ther; 9(1); 1-16. (C) 2010 AACR. C1 [Reinhold, William C.; Reimers, Mark A.; Lorenzi, Philip; Ho, Jennifer; Shankavaram, Uma T.; Ziegler, Micah S.; Bussey, Kimberly J.; Nishizuka, Satoshi; Ikediobi, Ogechi; Pommier, Yves G.; Weinstein, John N.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Reimers, Mark A.] Virginia Commonwealth Univ, Richmond, VA USA. [Lorenzi, Philip; Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Lorenzi, Philip; Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Shankavaram, Uma T.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bussey, Kimberly J.] Translat Genom Res Inst, Clin Translat Res Div, Phoenix, AZ USA. [Nishizuka, Satoshi] Iwate Med Univ, Sch Med, Dept Surg, Uchimaru, Japan. [Ikediobi, Ogechi] Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. RP Reinhold, WC (reprint author), 9000 Rockville Pike,Bldg 37,Room 5056, Bethesda, MD 20892 USA. EM wcr@mail.nih.gov; jweinste@mdanderson.org OI Bussey, Kimberly/0000-0003-1001-8207 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 50 TC 23 Z9 27 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2010 VL 9 IS 1 BP 1 EP 16 DI 10.1158/1535-7163.MCT-09-0321 PG 16 WC Oncology SC Oncology GA 606EM UT WOS:000278405000001 PM 20053763 ER PT J AU Houghton, PJ Morton, CL Gorlick, R Lock, RB Carol, H Reynolds, CP Kang, MH Maris, JM Keir, ST Kolb, EA Wu, JR Wozniak, AW Billups, CA Rubinstein, L Smith, MA AF Houghton, Peter J. Morton, Christopher L. Gorlick, Richard Lock, Richard B. Carol, Hernan Reynolds, C. Patrick Kang, Min H. Maris, John M. Keir, Stephen T. Kolb, E. Anders Wu, Jianrong Wozniak, Amy W. Billups, Catherine A. Rubinstein, Larry Smith, Malcolm A. TI Stage 2 Combination Testing of Rapamycin with Cytotoxic Agents by the Pediatric Preclinical Testing Program SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; PHASE-II TRIAL; MTOR INHIBITOR; IN-VIVO; ALKYLATING-AGENTS; RAD001 EVEROLIMUS; TUMOR XENOGRAFTS; CANCER MODELS; SINGLE-AGENT AB Rapamycin demonstrated broad-spectrum tumor growth inhibition activity against the in vivo panels of childhood tumors used in the Pediatric Preclinical Testing Program (PPTP). Here we have evaluated rapamycin combined with agents used frequently in the treatment of childhood malignancies. Rapamycin was tested in vitro against 23 cell lines alone or in combination with melphalan, cisplatin, vincristine, or dexamethasone (leukemic models only). In vivo, the impact of combining rapamycin with a cytotoxic agent was evaluated using two measures: 1) the therapeutic enhancement measure, and 2) a linear regression model for time-to-event to formally evaluate for sub- and supraadditivity for the combination compared to the agents used alone. Combining rapamycin with cytotoxic agents in vitro gave predominantly subadditive or additive effects, except for dexamethasone in leukemia models for which supra-additive activity was observed. In vivo testing demonstrated that therapeutic enhancement was common for rapamycin in combination with cyclophosphamide and occurred for 4 of 11 evaluable xenografts for the rapamycin and vincristine combination. The combinations of rapamycin with either cyclophosphamide or vincristine were significantly more effective than the respective standard agents used alone at their maximum tolerated doses (MTD) for most evaluable xenografts. The combination of rapamycin and cisplatin produced excessive toxicity requiring cisplatin dose reductions, and therapeutic enhancement was not observed for this combination. Addition of rapamycin to either cyclophosphamide or vincristine at their respective MTDs appears promising, as these combinations are relatively well tolerated and as many of the pediatric preclinical models evaluated demonstrated therapeutic enhancement for these combinations. Mol Cancer Ther; 9(1); 101-12. (C) 2010 AACR. C1 [Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childrens Canc, Columbus, OH 43205 USA. [Morton, Christopher L.; Wu, Jianrong; Wozniak, Amy W.; Billups, Catherine A.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Lock, Richard B.; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Rubinstein, Larry] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Ctr Childrens Canc, 700 Childrens Dr, Columbus, OH 43205 USA. EM Peter.Houghton@nationwidechildrens.org RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786] FX NO1-CM-42216, CA21765, and CA108786 from the National Cancer Institute. NR 39 TC 47 Z9 50 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2010 VL 9 IS 1 BP 101 EP 112 DI 10.1158/1535-7163.MCT-09-0952 PG 12 WC Oncology SC Oncology GA 606EM UT WOS:000278405000009 PM 20053767 ER PT J AU Alfano, RW Leppla, SH Liu, SH Bugge, TH Ortiz, JM Lairmore, TC Duesbery, NS Mitchell, IC Nwariaku, F Frankel, AE AF Alfano, Randall W. Leppla, Stephen H. Liu, Shihui Bugge, Thomas H. Ortiz, Janelle M. Lairmore, Terry C. Duesbery, Nicholas S. Mitchell, Ian C. Nwariaku, Fiemu Frankel, Arthur E. TI Inhibition of Tumor Angiogenesis by the Matrix Metalloproteinase-Activated Anthrax Lethal Toxin in an Orthotopic Model of Anaplastic Thyroid Carcinoma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PROTEIN-KINASE KINASE; RECEPTOR TYROSINE KINASES; HUMAN-MELANOMA CELLS; ATHYMIC NUDE-MICE; HEPATOCELLULAR-CARCINOMA; RAF/MEK/ERK PATHWAY; TISSUE INHIBITORS; BRAF MUTATION; B-RAF; CANCER AB Patients with anaplastic thyroid carcinoma (ATC) typically succumb to their disease months after diagnosis despite aggressive therapy. A large percentage of ATCs have been shown to harbor the V600E B-Raf point mutation, leading to the constitutive activation of the mitogen-activated protein kinase pathway. ATC invasion, metastasis, and angiogenesis are in part dependent on the gelatinase class of matrix metalloproteinases (MMP). The explicit targeting of these two tumor markers may provide a novel therapeutic strategy for the treatment of ATC. The MMP-activated anthrax lethal toxin (LeTx), a novel recombinant protein toxin combination, shows potent mitogen-activated protein kinase pathway inhibition in gelatinase-expressing V600E B-Raf tumor cells in vitro. However, preliminary in vivo studies showed that the MMP-activated LeTx also exhibited dramatic antitumor activity against xenografts that did not show significant antiproliferative responses to the LeTx in vitro. Here, we show that the MMP-activated LeTx inhibits orthotopic ATC xenograft progression in both toxin-sensitive and toxin-resistant ATC cells via reduced endothelial cell recruitment and subsequent tumor vascularization. This in turn translates to an improved long-term survival that is comparable with that produced by the multikinase inhibitor sorafenib. Our results also indicate that therapy with the MMP-activated LeTx is extremely effective against advanced tumors with well-established vascular networks. Taken together, these results suggest that the MMP-activated LeTx-mediated endothelial cell targeting is the primary in vivo antitumor mechanism of this novel toxin. Therefore, the MMP-activated LeTx could be used not only in the clinical management of V600E B-Raf ATC but potentially in any solid tumor. Mol Cancer Ther; 9(1); 190-201. (C) 2010 AACR. C1 [Alfano, Randall W.; Frankel, Arthur E.] Scott & White Mem Hosp & Clin, Canc Res Inst, Temple, TX 76502 USA. [Lairmore, Terry C.] Scott & White Mem Hosp & Clin, Dept Surg Oncol, Temple, TX 76502 USA. [Alfano, Randall W.; Ortiz, Janelle M.; Frankel, Arthur E.] Texas A&M Hlth Sci Ctr, Dept Internal Med, Temple, TX USA. [Leppla, Stephen H.; Liu, Shihui] NIAID, Lab Bacterial Dis, Bethesda, MD 20892 USA. [Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Duesbery, Nicholas S.] Van Andel Res Inst, Lab Canc & Dev Cell Biol, Grand Rapids, MI USA. [Mitchell, Ian C.] Univ Texas SW Med Ctr Dallas, Div Gastrointestinal & Endocrine Surg, Dept Surg, Dallas, TX 75390 USA. RP Frankel, AE (reprint author), Scott & White Mem Hosp & Clin, Canc Res Inst, 5701 S Airport Rd, Temple, TX 76502 USA. EM afrankel@swmail.sw.org OI DUESBERY, NICK/0000-0002-4258-5655 FU Department of Surgery, Scott and White Memorial Hospital; NIH; National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research FX Department of Surgery, Scott and White Memorial Hospital (T.C. Lairmore); Intramural Research Program of the NIH; National Institute of Allergy and Infectious Diseases; and National Institute of Dental and Craniofacial Research. NR 43 TC 13 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2010 VL 9 IS 1 BP 190 EP 201 DI 10.1158/1535-7163.MCT-09-0694 PG 12 WC Oncology SC Oncology GA 606EM UT WOS:000278405000017 PM 20053778 ER PT J AU Gloriam, DE Orchard, S Bertinetti, D Bjorling, E Bongcam-Rudloff, E Borrebaeck, CAK Bourbeillon, J Bradbury, ARM de Daruvar, A Dubel, S Frank, R Gibson, TJ Gold, L Haslam, N Herberg, FW Hiltke, T Hoheisel, JD Kerrien, S Koegl, M Konthur, Z Korn, B Landegren, U Montecchi-Palazzi, L Palcy, S Rodriguez, H Schweinsberg, S Sievert, V Stoevesandt, O Taussig, MJ Ueffing, M Uhlen, M van der Maarel, S Wingren, C Woollard, P Sherman, DJ Hermjakob, H AF Gloriam, David E. Orchard, Sandra Bertinetti, Daniela Bjorling, Erik Bongcam-Rudloff, Erik Borrebaeck, Carl A. K. Bourbeillon, Julie Bradbury, Andrew R. M. de Daruvar, Antoine Duebel, Stefan Frank, Ronald Gibson, Toby J. Gold, Larry Haslam, Niall Herberg, Friedrich W. Hiltke, Tara Hoheisel, Joerg D. Kerrien, Samuel Koegl, Manfred Konthur, Zoltan Korn, Bernhard Landegren, Ulf Montecchi-Palazzi, Luisa Palcy, Sandrine Rodriguez, Henry Schweinsberg, Sonja Sievert, Volker Stoevesandt, Oda Taussig, Michael J. Ueffing, Marius Uhlen, Mathias van der Maarel, Silvere Wingren, Christer Woollard, Peter Sherman, David J. Hermjakob, Henning TI A Community Standard Format for the Representation of Protein Affinity Reagents SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID ANTIBODY PROTEOMICS; RESOURCE; ATLAS; HER2 AB Protein affinity reagents (PARs), most commonly antibodies, are essential reagents for protein characterization in basic research, biotechnology, and diagnostics as well as the fastest growing class of therapeutics. Large numbers of PARs are available commercially; however, their quality is often uncertain. In addition, currently available PARs cover only a fraction of the human proteome, and their cost is prohibitive for proteome scale applications. This situation has triggered several initiatives involving large scale generation and validation of antibodies, for example the Swedish Human Protein Atlas and the German Antibody Factory. Antibodies targeting specific subproteomes are being pursued by members of Human Proteome Organisation (plasma and liver proteome projects) and the United States National Cancer Institute (cancer-associated antigens). ProteomeBinders, a European consortium, aims to set up a resource of consistently quality-controlled protein-binding reagents for the whole human proteome. An ultimate PAR database resource would allow consumers to visit one online warehouse and find all available affinity reagents from different providers together with documentation that facilitates easy comparison of their cost and quality. However, in contrast to, for example, nucleotide databases among which data are synchronized between the major data providers, current PAR producers, quality control centers, and commercial companies all use incompatible formats, hindering data exchange. Here we propose Proteomics Standards Initiative (PSI)-PAR as a global community standard format for the representation and exchange of protein affinity reagent data. The PSI-PAR format is maintained by the Human Proteome Organisation PSI and was developed within the context of ProteomeBinders by building on a mature proteomics standard format, PSI-molecular interaction, which is a widely accepted and established community standard for molecular interaction data. Further information and documentation are available on the PSI-PAR web site. Molecular & Cellular Proteomics 9: 1-10, 2010. C1 [Gloriam, David E.; Orchard, Sandra; Kerrien, Samuel; Montecchi-Palazzi, Luisa; Hermjakob, Henning] European Bioinformat Inst, Cambridge CB10 1SD, England. [Gloriam, David E.] Univ Copenhagen, Pharmaceut Fac, DK-2100 Copenhagen, Denmark. [Bertinetti, Daniela; Herberg, Friedrich W.; Schweinsberg, Sonja] Univ Kassel, Dept Biochem, D-34132 Kassel, Germany. [Bjorling, Erik; Uhlen, Mathias] AlbaNova Univ Ctr, Royal Inst Technol, SE-10691 Stockholm, Sweden. [Bongcam-Rudloff, Erik] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, S-75124 Uppsala, Sweden. [Bongcam-Rudloff, Erik] Swedish Univ Agr Sci, Linnaeus Ctr Bioinformat, S-75124 Uppsala, Sweden. [Bourbeillon, Julie; Sherman, David J.] Inst Natl Rech Informat & Automat Bordeaux Sud Ou, F-33405 Talence, France. [Bourbeillon, Julie; de Daruvar, Antoine; Palcy, Sandrine; Sherman, David J.] Univ Bordeaux, Lab Bordelais Rech Informat, CNRS 5800, F-33405 Talence, France. [Bradbury, Andrew R. M.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [de Daruvar, Antoine; Palcy, Sandrine] Univ Bordeaux, Ctr Bioinformat Bordeaux, F-33000 Bordeaux, France. [Duebel, Stefan] Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem & Biotechnol, D-38106 Braunschweig, Germany. [Frank, Ronald] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany. [Gibson, Toby J.; Haslam, Niall] European Mol Biol Lab, D-69117 Heidelberg, Germany. [Gold, Larry] SomaLogic Inc, Boulder, CO 80301 USA. [Hiltke, Tara; Rodriguez, Henry] NCI, NIH, Bethesda, MD 20892 USA. [Hoheisel, Joerg D.; Korn, Bernhard] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Koegl, Manfred] Resource Ctr Genome Res, D-69120 Heidelberg, Germany. [Konthur, Zoltan; Sievert, Volker] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Landegren, Ulf] Uppsala Univ, Dept Genet & Pathol, S-75185 Uppsala, Sweden. [Stoevesandt, Oda; Taussig, Michael J.] Babraham Biosci Technol Ltd, Cambridge CB22 3AT, England. [Ueffing, Marius] Res Ctr Environm Hlth, Dept Prot Sci, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany. [van der Maarel, Silvere] Leiden Univ, Med Ctr, NL-2300 RC Leiden, Netherlands. [Wingren, Christer] Lund Univ, Dept Immunotechnol, SE-22184 Lund, Sweden. [Woollard, Peter] GlaxoSmithKline Inc, Harlow CM19 5AW, Essex, England. [Borrebaeck, Carl A. K.] Lund Univ, BMC D13, Dept Immunotechnol, CREATE Hlth, Lund, Sweden. RP Gloriam, DE (reprint author), European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. RI Sievert, Volker/F-8432-2010; Gloriam, David/A-1904-2011; martel, celine/M-9779-2014; Bertinetti, Daniela/B-5655-2015; Herberg, Friedrich/B-5572-2015; Konthur, Zoltan/E-4575-2010; Bourbeillon, Julie/N-4832-2015 OI Gibson, Toby James/0000-0003-0657-5166; Orchard, Sandra/0000-0002-8878-3972; Hermjakob, Henning/0000-0001-8479-0262; Bradbury, Andrew/0000-0002-5567-8172; Dubel, Stefan/0000-0001-8811-7390; Gloriam, David/0000-0002-4299-7561; Kerrien, Samuel/0000-0002-3013-0469; martel, celine/0000-0002-1800-4558; Herberg, Friedrich/0000-0001-7117-7653; Konthur, Zoltan/0000-0002-8767-9823; Bourbeillon, Julie/0000-0002-3365-1286 FU ProteomeBinders European Commission (EC) [RI-CA 026008]; EC [21211]; European Science Foundation FX This work was authored, in whole or in part, by National Institutes of Health staff. This work was supported by the ProteomeBinders European Commission (EC) FP6 research infrastructures coordination action (Grant RI-CA 026008) and the EC FP7 Biobanking and Biomolecular Resource Infrastructure (Grant Agreement 21211) within WP4.; The on-line version of this article (available at http://www.mcponline.org) contains supplemental data 1-7.; Additionally supported by the European Science Foundation and its functional genomics program in the form of a postdoctoral fellowship. To whom correspondence should be addressed. Tel.: 46703148390; Fax: 4535336040; E-mail: par@psidev.info. NR 21 TC 23 Z9 23 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JAN PY 2010 VL 9 IS 1 BP 1 EP 10 DI 10.1074/mcp.M900185-MCP200 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 568EV UT WOS:000275505900001 PM 19674966 ER PT S AU Montoya, ID McCann, DJ AF Montoya, Ivan D. McCann, David J. BE Luch, A TI Drugs of abuse: management of intoxication and antidotes SO MOLECULAR, CLINICAL AND ENVIRONMENTAL TOXICOLOGY VOL 2: CLINICAL TOXICOLOGY SE Experientia Supplementum LA English DT Article; Book Chapter ID ACUTE-RENAL-FAILURE; CHROMATOGRAPHY-MASS-SPECTROMETRY; ACUTE PHENCYCLIDINE INTOXICATION; PLASMA CHOLINESTERASE ACTIVITY; INDUCED RESPIRATORY DEPRESSION; THERAPEUTIC COCAINE VACCINE; PRESUMED OPIOID OVERDOSE; LONG-TERM REDUCTIONS; INTENSIVE-CARE-UNIT; MONOCLONAL-ANTIBODY AB Illicit drug intoxications are an increasing public health problem for which, in most cases, no antidotes are clinically available. The diagnosis and treatment of these intoxications requires a trained clinician with experience in recognizing the specific signs and symptoms of intoxications to individual drugs as well as polydrug intoxications, which are more the rule than the exception. To make the diagnosis, the clinical observation and a urine toxicology test are often enough. Evaluating the blood levels of drugs is frequently not practical because the tests can be expensive and results may be delayed and unavailable to guide the establishment of a treatment plan. Other laboratory tests may be useful depending on the drug or drugs ingested and the presence of other medical complications. The treatment should be provided in a quiet, safe and reassuring environment. Vital signs should be closely monitored. Changes in blood pressure, respiratory frequency and temperature should be promptly treated, particularly respiratory depression (in cases of opiate intoxication) or hyperthermia (in cases of cocaine or amphetamine intoxication). Intravenous fluids should be administered as soon as possible. Other psychiatric and medical complication should receive appropriate symptomatic treatment. Research on immunotherapies, including vaccines, monoclonal and catalytic antibodies. seems to be a promising approach that may yield specific antidotes for drugs of abuse, helping to ameliorate the morbidity and mortality associated with illicit drug intoxications. C1 [Montoya, Ivan D.; McCann, David J.] NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Montoya, ID (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM imontoya@mail.nih.gov; dmccann@nida.nih.gov NR 200 TC 7 Z9 8 U1 0 U2 2 PU BIRKHAUSER BOSTON PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139-2333 USA SN 1023-294X BN 978-3-7643-8337-4 J9 EXPERIENTIA SUPPL JI Exp. Suppl. PY 2010 VL 100 BP 519 EP 541 D2 10.1007/978-3-7643-8338-1 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BNC16 UT WOS:000274143800015 PM 20358694 ER PT J AU Gold, B AF Gold, Bert BE Patrinos, GP Ansorge, WJ TI Automated DNA Hybridization and Detection SO MOLECULAR DIAGNOSTICS, 2ND EDITION LA English DT Article; Book Chapter ID REVERSE DOT-BLOT; COMPARATIVE GENOMIC HYBRIDIZATION; POLYMERASE-CHAIN-REACTION; FACTOR-V-LEIDEN; ASSAY; MUTATIONS; PCR; AMPLIFICATION; TIME; SAMPLES C1 NCI, Human Genet Sect, Canc & Inflammat Program, Ctr Canc Res,Lab Genom Divers, Frederick, MD 21702 USA. RP Gold, B (reprint author), NCI, Human Genet Sect, Canc & Inflammat Program, Ctr Canc Res,Lab Genom Divers, Bldg 560,Room 21-21, Frederick, MD 21702 USA. NR 48 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092318-5 PY 2010 BP 501 EP 511 DI 10.1016/B978-0-12-374537-8.00034-1 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCO38 UT WOS:000310852300037 ER PT J AU Grodzinski, P Ward, M Liu, R Scott, K Surrey, S Fortina, P AF Grodzinski, Piotr Ward, Michael Liu, Robin Scott, Kathryn Surrey, Saul Fortina, Paolo BE Patrinos, GP Ansorge, WJ TI The Use of Microelectronic-Based Techniques in Molecular Diagnostic Assays SO MOLECULAR DIAGNOSTICS, 2ND EDITION LA English DT Article; Book Chapter ID POLYMERASE-CHAIN-REACTION; DENSITY DNA ARRAYS; CAPILLARY-ELECTROPHORESIS; OLIGONUCLEOTIDE ARRAYS; MUTATION DETECTION; SEMICONDUCTOR MICROCHIPS; PCR AMPLIFICATION; GENETIC-ANALYSIS; CELL-SEPARATION; ANALYSIS SYSTEM C1 [Grodzinski, Piotr] NCI, Ctr Strateg & Sci Initiat, Bethesda, MD 20892 USA. [Ward, Michael] Invitrogene Corp, Eugene, OR USA. [Liu, Robin] Osmetech Mol Diagnost, Mol Diagnost, Pasadena, CA USA. [Scott, Kathryn; Fortina, Paolo] Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA. [Surrey, Saul] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. [Fortina, Paolo] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. [Surrey, Saul] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA. [Surrey, Saul] Thomas Jefferson Univ, Div Hematol, Philadelphia, PA 19107 USA. [Scott, Kathryn] Thomas Jefferson Univ, Dept Med, Ctr Translat Med Genom, Philadelphia, PA 19107 USA. RP Grodzinski, P (reprint author), NCI, Ctr Strateg & Sci Initiat, Bethesda, MD 20892 USA. NR 85 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092318-5 PY 2010 BP 513 EP 526 DI 10.1016/B978-0-12-374537-8.00035-3 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCO38 UT WOS:000310852300038 ER PT J AU Simon, R AF Simon, Richard BE Jorgensen, JT Winther, H TI DRUG AND PHARMACODIAGNOSTIC CO-DEVELOPMENT: STATISTICAL CONSIDERATIONS SO MOLECULAR DIAGNOSTICS: THE KEY DRIVER IN PERSONALIZED CANCER MEDICINE LA English DT Article; Book Chapter ID RANDOMIZED CLINICAL-TRIALS; GENE-EXPRESSION PROFILES; DNA MICROARRAY DATA; BREAST-CANCER; CLASS PREDICTION; END-POINTS; CLASSIFICATION; ANTHRACYCLINES; CLASSIFIERS; VALIDATION C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 34 TC 0 Z9 0 U1 0 U2 0 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-9-81424-145-8 PY 2010 BP 207 EP 225 PG 19 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BTV86 UT WOS:000288202600011 ER PT J AU Seminara, J Tuchman, M Krivitzky, L Krischer, J Lee, HS LeMons, C Baumgartner, M Cederbaum, S Diaz, GA Feigenbaum, A Gallagher, RC Harding, CO Kerr, DS Lanpher, B Lee, B Lichter-Konecki, U McCandless, SE Merritt, JL Oster-Granite, ML Seashore, MR Stricker, T Summar, M Waisbren, S Yudkoff, M Batshaw, ML AF Seminara, Jennifer Tuchman, Mendel Krivitzky, Lauren Krischer, Jeffrey Lee, Hye-Seung LeMons, Cynthia Baumgartner, Matthias Cederbaum, Stephen Diaz, George A. Feigenbaum, Annette Gallagher, Renata C. Harding, Cary O. Kerr, Douglas S. Lanpher, Brendan Lee, Brendan Lichter-Konecki, Uta McCandless, Shawn E. Merritt, J. Lawrence Oster-Granite, Mary Lou Seashore, Margretta R. Stricker, Tamar Summar, Marshall Waisbren, Susan Yudkoff, Marc Batshaw, Mark L. TI Establishing a consortium for the study of rare diseases: The Urea Cycle Disorders Consortium SO MOLECULAR GENETICS AND METABOLISM LA English DT Article; Proceedings Paper CT 3rd International Satellite on Urea Cycle Disorders CY AUG 27-29, 2009 CL La Jolla, CA DE Urea cycle disorder; Rare disease ID ORNITHINE TRANSCARBAMYLASE DEFICIENCY; ENZYMOPATHIES; PHENOTYPE; CHILDREN AB The Urea Cycle Disorders Consortium (UCDC) was created as part of a larger network established by the National Institutes of Health to study rare diseases. This paper reviews the UCDC's accomplishments over the first 6 years, including how the Consortium was developed and organized, clinical research studies initiated, and the importance of creating partnerships with patient advocacy groups, philanthropic foundations and biotech and pharmaceutical companies. Published by Elsevier Inc. C1 [Seminara, Jennifer; Tuchman, Mendel; Krivitzky, Lauren; Lichter-Konecki, Uta; Batshaw, Mark L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Krischer, Jeffrey; Lee, Hye-Seung] Univ S Florida, Data Management & Coordinating Ctr, Tampa, FL USA. [LeMons, Cynthia] Natl Urea Cycle Disorders Fdn, Pasadena, CA USA. [Baumgartner, Matthias; Stricker, Tamar] Univ Childrens Hosp, Zurich, Switzerland. [Cederbaum, Stephen] Univ Calif Los Angeles, Los Angeles, CA USA. [Diaz, George A.] Mt Sinai Sch Med, New York, NY USA. [Feigenbaum, Annette] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Gallagher, Renata C.] Childrens Hosp, Aurora, CO USA. [Harding, Cary O.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kerr, Douglas S.; McCandless, Shawn E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Lanpher, Brendan; Summar, Marshall] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Lee, Brendan] Baylor Coll Med, Houston, TX 77030 USA. [Merritt, J. Lawrence] Seattle Childrens Hosp, Seattle, WA USA. [Seashore, Margretta R.] Yale Univ, New Haven, CT USA. [Waisbren, Susan] Childrens Hosp, Boston, MA 02115 USA. [Yudkoff, Marc] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Oster-Granite, Mary Lou] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Intellectual & Dev Disabil Branch, Bethesda, MD USA. RP Batshaw, ML (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. EM mbatshaw@cnmc.org OI Merritt, II, John Lawrence/0000-0002-2552-7306; Baumgartner, Matthias R./0000-0002-9270-0826 FU NCRR NIH HHS [U54 RR019453, U54 RR019453-01, U54RR019453]; NICHD NIH HHS [U54 HD061221]; NIDDK NIH HHS [K08 DK074573] NR 18 TC 32 Z9 35 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PY 2010 VL 100 SU S BP S97 EP S105 DI 10.1016/j.ymgme.2010.01.014 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 587IS UT WOS:000276985100017 PM 20188616 ER PT J AU Skovby, F Gaustadnes, M Mudd, SH AF Skovby, Flemming Gaustadnes, Mette Mudd, S. Harvey TI A revisit to the natural history of homocystinuria due to cystathionine beta-synthase deficiency SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Cystathionine beta-synthase; Deficiency; Homocystinuria; 1278T; Ascertainment bias; Natural history ID BIRTH PREVALENCE; MUTATION; GENE; FREQUENCY AB We review the evidence that in Denmark and probably certain other European countries the number of individuals identified with homocystinuria due to homozygosity for the widespread c.833T>C (p.1278T) mutation in the gene that encodes cystathionine beta-synthase (CBS) falls far short of the number of such individuals expected on the basis of the heterozygote frequency for this mutation found by molecular screening. We conclude that the predominant portion of such homozygotes may be clinically unaffected, or may be ascertained for thromboembolic events occurring no sooner than the third decade of life. If so, there was significant ascertainment bias in the time-to-event curves previously published describing the natural history of untreated CBS deficiency Mudd et al. [5] and these curves should be used with care. (C) 2009 Elsevier Inc. All rights reserved. C1 [Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. [Skovby, Flemming] Univ Copenhagen, Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark. [Gaustadnes, Mette] Aarhus Univ Hosp Skejby, Dept Mol Med, Aarhus, Denmark. RP Mudd, SH (reprint author), NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. EM muddh@mail.nih.gov FU National Institute of Mental Health FX This work was supported in part by the Intramural Program of the National Institute of Mental Health. We are grateful to departments of clinical biochemistry in Denmark for providing homocysteine results of thrombophilia screening. NR 20 TC 40 Z9 43 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2010 VL 99 IS 1 BP 1 EP 3 DI 10.1016/j.ymgme.2009.09.009 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 545SV UT WOS:000273758000001 PM 19819175 ER PT J AU Liu, ZF Liu, SL Niu, G Wang, F Liu, S Chen, XY AF Liu, Zhaofei Liu, Shuanglong Niu, Gang Wang, Fan Liu, Shuang Chen, Xiaoyuan TI Optical Imaging of Integrin alpha(v)beta(3) Expression with Near-Infrared Fluorescent RGD Dimer with Tetra(ethylene glycol) Linkers SO MOLECULAR IMAGING LA English DT Article ID TUMOR ANGIOGENESIS; CONTRAST AGENTS; CANCER-THERAPY; PEPTIDES; PET; TOMOGRAPHY AB Integrin alpha(v)beta(3) plays great roles in tumor angiogenesis, invasion, and metastasis. We report here the noninvasive visualization of tumor integrin alpha(v)beta(3) expression by using near-infrared fluorescence (NIRF) imaging of an IRDye800-labeled new cyclic RGD (arginine-glycine-aspartic acid) dimer with tetra(ethylene glycol) (PEG(4)) linkers (ie, E[PEG(4)-c(RGDfK)](2), PEG(4) = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) in a U87MG tumor model. Fluorescent dye-labeled E[PEG(4)-c(RGDfK)](2) were subjected to in vitro cell staining, in vivo NIRF imaging, ex vivo NIRF imaging, and histologic studies. The in vitro and in vivo characterization of dye-labeled E[PEG(4)-c(RGDfK)](2) were compared with dye-labeled RGD dimer without PEG(4) linkers (namely, E[c(RGDfK)](2)). Both Cy5.5-E[PEG(4)-c(RGDfK)](2) and Cy5.5-E[c(RGDfK)](2) exhibited integrin alpha(v)beta(3) binding specificity in a cell-staining experiment. In vivo NIRF imaging showed higher tumor accumulation and tumor to background contrast of IRDye800-E[PEG(4)-c(RGDfK)](2) over IRDye800-E[c(RGDfK)](2). The tumor integrin alpha(v)beta(3) specificity of IRDye800-E[PEG(4)-c(RGDfK)](2) was confirmed by successful inhibition of tumor uptake in the presence of an excess dose of c(RGDfK). Histologic examination revealed both tumor vasculature and tumor cell integrin alpha(v)beta(3) binding of IRDye800-E[PEG(4)-c(RGDfK)](2) in vivo. In summary, NIRF imaging with IRDye800-E[PEG(4)-c(RGDfK)](2) offers an easy, fast, and low-cost way to detect and semiquantify tumor integrin alpha(v)beta(3) expression in living subjects. C1 [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, CC, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Mol Imaging Program Stanford, Dept Radiol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Mol Imaging Program Stanford, Dept Biophys, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Bio X Program, Stanford, CA 94305 USA. Peking Univ, Med Isotopes Res Ctr, Beijing 100871, Peoples R China. Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed, CC, NIH, 31 Ctr Dr,31-1C22, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov RI Liu, Sheng/K-2815-2013 FU National Cancer Institute [R01 120188, R01 CA119053, R21 CA121842, R21 CA102123, P50 CA114747, U54 CA119367, R24 CA93862, R01 CA115883]; Department of Energy [DE-FG02-08ER64684]; China Scholarship Council FX This work was supported, in part, by the National Cancer Institute (R01 120188, R01 CA119053, R21 CA121842, R21 CA102123, P50 CA114747, U54 CA119367, and R24 CA93862 [to X.C.] and R01 CA115883 [to S.L.]); and the Department of Energy (DE-FG02-08ER64684 (to S.L.]). Zhaofei Liu acknowledges the China Scholarship Council for partial financial support during his study at Stanford University. NR 36 TC 28 Z9 30 U1 1 U2 9 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD JAN-FEB PY 2010 VL 9 IS 1 BP 21 EP 29 DI 10.2310/7290.2009.00032 PG 9 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 551SD UT WOS:000274228900002 PM 20128995 ER PT J AU Chen, WZ Zhu, ZY Feng, Y Dimitrov, DS AF Chen, Weizao Zhu, Zhongyu Feng, Yang Dimitrov, Dimiter S. TI A large human domain antibody library combining heavy and light chain CDR3 diversity SO MOLECULAR IMMUNOLOGY LA English DT Article DE Human domain antibody; Library; Phage display; Light chain CDR3; Grafting ID BINDING-PROTEINS; IMMUNOGLOBULIN FORMS; VARIABLE DOMAINS; PHAGE; CONSTRUCTION; REPERTOIRE; SCAFFOLDS; FV AB Domain antibodies (dAbs) are promising candidate therapeutics and diagnostics. Efficient selection of novel potent dAbs with potential for clinical utility is critically dependent on the library diversity and size, and the scaffold stability. We have previously constructed a large (size similar to 2.5 x 10(10)) dAb library by grafting human antibody heavy chain complementarity determining regions (CDRs) 2 and 3 (H2s, H3s) into their cognate positions in a human heavy chain variable domain (VH) scaffold and mutagenizing the CDR1 (HI). High-affinity binders against some antigens were selected from this library but panning against others was not very successful likely due to limited diversity. We have hypothesized that by grafting highly variable, both in length and composition, human CDRs into non-cognate positions, the dAb library diversity could be significantly increased and the library would allow for more efficient selection of high-affinity antibodies against some targets. To test this hypothesis we designed a novel type of dAb library containing CDRs in non-cognate positions. It is based on our previous library where H1 was replaced by a library of human light chain CDR3s (L3s) thus combining three most diversified fragments (L3, H3 and H2) in one VH scaffold. This large (size similar to 10(10)) phage-displayed library was highly diversified as determined by analyzing the sequences of 126 randomly selected clones. Novel high-affinity dAbs against components of the human insulin-like growth factor (IGF) system were selected from the new library that could not be selected from the previously constructed one. Most of the newly identified dAbs were highly soluble, expressible, monomeric and may have potential as candidate cancer therapeutics. The new library could be used not only for the selection of such dAbs thus complementing existing libraries but also as a research tool for the exploration of the mechanisms determining folding and stability of human antibody domains. Published by Elsevier Ltd. C1 [Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. [Zhu, Zhongyu] NCI, Basic Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, CCRNP, CCR,NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA. EM dimiter.dimitrov@nih.gov FU NIH [N01-CO-12400] FX This work was supported by the NIH Intramural AIDS Targeted Antiviral Program, by the NIH National Institute of Allergy and Infectious Diseases Intramural Biodefense Program (DSD), by the NIH NCI Center for Cancer Research Intramural Research Program, and by federal funds from the NIH NCI under contract N01-CO-12400. NR 24 TC 11 Z9 12 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2010 VL 47 IS 4 BP 912 EP 921 DI 10.1016/j.molimm.2009.09.039 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 555JS UT WOS:000274507400034 PM 19883941 ER PT J AU Wang, Q Liu, CM Zhu, FL Liu, FM Zhang, P Guo, C Wang, XY Li, HY Ma, CH Sun, WS Zhang, Y Chen, WJ Zhang, LN AF Wang, Qun Liu, Chunmei Zhu, Faliang Liu, Fengming Zhang, Pin Guo, Chun Wang, Xiaoyan Li, Haiyan Ma, Chunhong Sun, Wensheng Zhang, Yun Chen, WanJun Zhang, Lining TI Reoxygenation of hypoxia-differentiated dentritic cells induces Th1 and Th17 cell differentiation SO MOLECULAR IMMUNOLOGY LA English DT Article DE Dendritic cells; Inflammation; Foxp3(+) Tregs; IL-6; TGF-beta; Hypoxia ID REGULATORY T-CELLS; ISCHEMIA-REPERFUSION INJURY; IMMUNOLOGICAL SELF-TOLERANCE; MOUSE BONE-MARROW; DENDRITIC CELLS; ISCHEMIA/REPERFUSION INJURY; TGF-BETA; IN-VIVO; MECHANISMS; RECEPTOR AB Dendritic cells (DCs) are often exposed to various oxygen tensions under physiological and pathological conditions. However, the effects of various Oxygen tensions on DC functions remain unclear. In this study, we showed that hypoxia-differentiated DCs expressed lower levels of MHC-II molecule, co-stimulatory molecules (CD80, CD86) and proinflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha), but higher levels of immunoregulatory cytokine transforming growth factor-beta (TGF-beta) than normoxia-differentiated DCs. Unexpectedly, re-exposure of hypoxia-differentiated DCs to saturated oxygen (reoxygenation) completely restored their mature phenotype and function. Specifically, the reoxygenated DCs induced naive CD4(+) T cells to differentiate into Th1 and Th17 effector cells, but deceased the generation of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). The data indicate that hypoxic microenvironment suppresses the maturation and function of murine DCs. Reoxygenation of hypoxia-differentiated DCs however results in complete recovery of their mature phenotype and function, and has strong ability to drive immune response toward a proinflammatory direction, suggesting reoxygenated DCs may contribute to inflammation of ischemia-reperfusion injury. Published by Elsevier Ltd. C1 [Zhang, Pin; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, OIIB, NIH, Bethesda, MD 20892 USA. [Wang, Qun; Liu, Chunmei; Zhu, Faliang; Liu, Fengming; Guo, Chun; Wang, Xiaoyan; Li, Haiyan; Ma, Chunhong; Sun, Wensheng; Zhang, Lining] Shandong Univ, Dept Immunol, Sch Med, Jinan 250012, Peoples R China. [Zhang, Yun] Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Peoples R China. [Zhang, Yun] Shandong Univ, Chinese Minist Hlth, Qilu Hosp, Jinan 250012, Peoples R China. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, OIIB, NIH, Bethesda, MD 20892 USA. EM wchen@mail.nih.gov; immuno@sdu.edu.cn RI ma, chunhong/C-6043-2008 FU National Natural Science Foundation of China [30628015, 30700729]; National "973" program of China [2006CB503803]; Natural Science Foundation of Shandong Province, China [Q2007C02]; Intramural Research Program of the NIH; NIDCR, USA FX This Study was supported by research funding from the National Natural Science Foundation of China (30628015, 30700729), National "973" program of China (2006CB503803) and Natural Science Foundation of Shandong Province, China (Q2007C02) and the Intramural Research Program of the NIH, NIDCR, USA. We thank Dr. Youhai Chen, University of Pennsylvania, USA and Xun Qu, Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, China for critical discussions on this manuscript. NR 52 TC 24 Z9 24 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2010 VL 47 IS 4 BP 922 EP 931 DI 10.1016/j.molimm.2009.09.038 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 555JS UT WOS:000274507400035 PM 19910049 ER PT J AU Swingle, B Markel, E Costantino, N Bubunenko, MG Cartinhour, S Court, DL AF Swingle, Bryan Markel, Eric Costantino, Nina Bubunenko, Mikhail G. Cartinhour, Samuel Court, Donald L. TI Oligonucleotide recombination in Gram-negative bacteria SO MOLECULAR MICROBIOLOGY LA English DT Article ID SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; SYNTHETIC OLIGONUCLEOTIDES; BETA-PROTEIN; HOMOLOGOUS RECOMBINATION; PSEUDOMONAS-AERUGINOSA; PROMOTES RENATURATION; ANNEALING PROTEINS; LAMBDA; RED AB This report describes several key aspects of a novel form of RecA-independent homologous recombination. We found that synthetic single-stranded DNA oligonucleotides (oligos) introduced into bacteria by transformation can site-specifically recombine with bacterial chromosomes in the absence of any additional phage-encoded functions. Oligo recombination was tested in four genera of Gram-negative bacteria and in all cases evidence for recombination was apparent. The experiments presented here were designed with an eye towards learning to use oligo recombination in order to bootstrap identification and development of phage-encoded recombination systems for recombineering in a wide range of bacteria. The results show that oligo concentration and sequence have the greatest influence on recombination frequency, while oligo length was less important. Apart from the utility of oligo recombination, these findings also provide insights regarding the details of recombination mediated by phage-encoded functions. Establishing that oligos can recombine with bacterial genomes provides a link to similar observations of oligo recombination in archaea and eukaryotes suggesting the possibility that this process is evolutionary conserved. C1 [Swingle, Bryan; Markel, Eric; Cartinhour, Samuel] USDA ARS, Ithaca, NY 14853 USA. [Swingle, Bryan; Markel, Eric; Cartinhour, Samuel] Cornell Univ, Dept Plant Pathol & Plant Microbe Biol, Ithaca, NY 14853 USA. [Costantino, Nina; Court, Donald L.] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Bubunenko, Mikhail G.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Swingle, B (reprint author), USDA ARS, Ithaca, NY 14853 USA. EM Bryan.Swingle@ars.usda.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research; National Institutes of Allergy and Infectious Disease FX We thank Philip Bronstein, Melanie Filiatrault, Chris Myers, Jim Sawitzke, David Schneider and Lynn Thomason for many useful discussions. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and in part by a Trans National Institutes of Health/Food and Drug Administration Intramural Biodefense Program Grant of National Institutes of Allergy and Infectious Disease (to D. L. C.). NR 43 TC 47 Z9 51 U1 0 U2 15 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2010 VL 75 IS 1 BP 138 EP 148 DI 10.1111/j.1365-2958.2009.06976.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 536UE UT WOS:000273068500012 PM 19943907 ER PT J AU Choi, PS Bernstein, HD AF Choi, Peter S. Bernstein, Harris D. TI Sequential translocation of an Escherchia coli two-partner secretion pathway exoprotein across the inner and outer membranes SO MOLECULAR MICROBIOLOGY LA English DT Article ID PERTUSSIS FILAMENTOUS HEMAGGLUTININ; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; PROTEIN SECRETION; SERRATIA-MARCESCENS; DOMAINS; FHAC; AUTOTRANSPORTER; HEMOLYSIN; SIGNAL AB In Gram-negative bacteria, a variety of high molecular weight 'exoproteins' are translocated across the outer membrane (OM) via the two-partner secretion (TPS) pathway by interacting with a dedicated transporter. It is unclear, however, whether the translocation of exoproteins across the OM is coupled to their translocation across the inner membrane (IM). To address this question, we separated the production of an Escherichia coli O157:H7 exoprotein (OtpA) and its transporter (OtpB) temporally by placing otpA and otpB under the control of distinct regulatable promoters. We found that when both full-length and truncated forms of OtpA were expressed prior to OtpB, a significant fraction of the exoprotein was secreted. The results indicate that OtpA can be translocated into the periplasm and briefly remain secretion-competent. Furthermore, by engineering cysteine residues into OtpA and using disulphide bond formation as a reporter of periplasmic localization, we obtained additional evidence that the C-terminus of OtpA enters the periplasm before the N-terminus is translocated across the OM even when OtpA and OtpB are expressed simultaneously. Taken together, our results demonstrate that the translocation of a TPS exoprotein across the OM can occur independently from its translocation across the IM. C1 [Choi, Peter S.; Bernstein, Harris D.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM harris_bernstein@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Janine Peterson for providing outstanding technical assistance, Rob Boulianne for generating the anti-YidC antiserum and Yihong Ye for providing helpful comments on the manuscript. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 34 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2010 VL 75 IS 2 BP 440 EP 451 DI 10.1111/j.1365-2958.2009.06993.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 544DM UT WOS:000273632700015 PM 19968793 ER PT S AU Washington, KN Tisdale, JF Hsieh, MM AF Washington, Kareem N. Tisdale, John F. Hsieh, Matthew M. BE Dunphy, CH TI Gene Therapy for Nonneoplastic Hematologic and Histiocytic Disorders SO MOLECULAR PATHOLOGY OF HEMATOLYMPHOID DISEASES SE Molecular Pathology Library LA English DT Article; Book Chapter ID SEVERE COMBINED IMMUNODEFICIENCY; ADENOASSOCIATED VIRUS VECTORS; HEMATOPOIETIC STEM-CELLS; AUTOLOGOUS BONE-MARROW; SEVERE HEMOPHILIA-A; ANEMIA GROUP-C; IN-VIVO; NONDIVIDING CELLS; FANCONI-ANEMIA; REPOPULATING CELLS C1 [Washington, Kareem N.; Tisdale, John F.; Hsieh, Matthew M.] NIDDK, NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. RP Washington, KN (reprint author), NIDDK, NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. NR 109 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1935-987X BN 978-1-4419-5697-2 J9 MOL PATHOL LIB PY 2010 BP 597 EP 608 DI 10.1007/978-1-4419-5698-9_45 D2 10.1007/978-1-4419-5698-9 PG 12 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA BOR14 UT WOS:000277366500045 ER PT J AU Kumar, V Hong, SY Maciag, AE Saavedra, JE Adamson, DH Prud'homme, RK Keefer, LK Chakrapani, H AF Kumar, Varun Hong, Sam Y. Maciag, Anna E. Saavedra, Joseph E. Adamson, Douglas H. Prud'homme, Robert K. Keefer, Larry K. Chakrapani, Harinath TI Stabilization of the Nitric Oxide (NO) Prodrugs and Anticancer Leads, PABA/NO and Double JS-K, through Incorporation into PEG-Protected Nanoparticles SO MOLECULAR PHARMACEUTICS LA English DT Article DE Nitric oxide; PABA/NO; glutathione; glutathione S-transferase; nanoparticles; formulation ID IN-VITRO; S-GLUTATHIONYLATION; DRUG-DELIVERY; ANTILEUKEMIC ACTIVITY; MACROMOLECULAR DRUGS; CANCER-CHEMOTHERAPY; STRUCTURAL ANALOGS; NOBEL LECTURE; TUMOR-CELLS; PROTEINS AB We report the stabilization of the nitric oxide (NO) prodrugs and anticancer lead compounds, PABA/NO (O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N, N-dimethylamino)diazen-1-ium-1,2-diolate) and "Double JS-K" 1,5-bis-{1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diol-2-diol-2,4-dinitrobenzene, through their incorporation into polymer-protected nanoparticles. The prodrugs were formulated in block copolymer-stabilized nanoparticles with sizes from 220 to 450 nm by a novel rapid precipitation process. The block copolymers, with polyethylene glycol (PEG) soluble blocks, provide a steric barrier against NO prodrug activation by glutathione. Too rapid activation and NO release has been a major barrier to effective administration of this class of compounds. The nanoparticle stabilized PABA/NO are protected from attack by glutathione as evidenced by a significant increase in time taken for 50% decomposition from 15 min (unformulated) to 5 h (formulated); in the case of Double JS-K, the 50% decomposition time was extended from 4.5 min (unformulated) to 40 min (formulated). The more hydrophobic PABA/NO produced more stable nanoparticles and correspondingly more extended release times in comparison with Double JS-K. The hydrophobic blocks of the polymer were either polystyrene or polylactide, Both blocks produced nanoparticles of approximately the same size and release kinetics. This combination of PEG-protected nanoparticles with sizes appropriate for cancer targeting by enhanced permeation and retention (EPR) and delayed release of NO may afford enhanced therapeutic benefit. C1 [Kumar, Varun; Prud'homme, Robert K.] Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. [Hong, Sam Y.; Keefer, Larry K.] NCI, Chem Sect, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. [Maciag, Anna E.; Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21702 USA. [Adamson, Douglas H.] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA. [Adamson, Douglas H.] Univ Connecticut, Inst Mat Sci, Storrs, CT 06269 USA. RP Prud'homme, RK (reprint author), Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. EM prudhomm@princeton.edu; harinath@iiserpune.ac.in RI Kumar, Varun/H-6159-2011; Keefer, Larry/N-3247-2014; Adamson, Douglas/C-8721-2009 OI Keefer, Larry/0000-0001-7489-9555; FU NIH; National Cancer Institute [HHSN261200800001E]; Center for Cancer Research; National Science Foundation [CBET 0506966] FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, as well as by National Cancer Institute Contract HHSN261200800001E and the National Science Foundation under the NIRT grant for Nanoparticle Formation Technologies (CBET 0506966). NR 46 TC 29 Z9 29 U1 3 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JAN-FEB PY 2010 VL 7 IS 1 BP 291 EP 298 DI 10.1021/mp900245h PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 549BN UT WOS:000274015900030 PM 20000791 ER PT J AU Liu, FL Gan, ZT Shao, YH Hsu, CP Dreuw, A Head-Gordon, M Miller, BT Brooks, BR Yu, JG Furlani, TR Kong, J AF Liu, Fenglai Gan, Zhengting Shao, Yihan Hsu, Chao-Ping Dreuw, Andreas Head-Gordon, Martin Miller, Benjamin T. Brooks, Bernard R. Yu, Jian-Guo Furlani, Thomas R. Kong, Jing TI A parallel implementation of the analytic nuclear gradient for time-dependent density functional theory within the Tamm-Dancoff approximation SO MOLECULAR PHYSICS LA English DT Article; Proceedings Paper CT International Conference on Molecular Quantum Mechanics CY MAY 24-29, 2010 CL Univ California, Berkeley, CA SP Dell Computer, Hewlett-Packard, Virginia Tech Coll Sci, Q-Chem Inc, Amer Inst Phys HO Univ California DE excited states; time-dependent density functional theory; analytical gradient; density functional theory ID EXCITED-STATES; EXCITATION-ENERGIES; LINEAR-RESPONSE; DERIVATIVES; EXCHANGE; SET AB We derived the analytic gradient for the excitation energies from a time-dependent density functional theory calculation within the Tamm-Dancoff approximation (TDDFT/TDA) using Gaussian atomic orbital basis sets, and introduced an efficient serial and parallel implementation. Some timing results are shown from a B3LYP/6-31G**/SG-1-grid calculation on zincporphyrin. We also performed TDDFT/TDA geometry optimizations for low-lying excited states of 20 small molecules, and compared adiabatic excitation energies and optimized geometry parameters to experimental values using the B3LYP and B97 functionals. There are only minor differences between TDDFT and TDA optimized excited state geometries and adiabatic excitation energies. Optimized bond lengths are in better agreement with experiment for both functionals than either CC2 or SOS-CIS(D0), while adiabatic excitation energies are in similar or slightly poorer agreement. Optimized bond angles with both functionals are more accurate than CIS values, but less accurate than either CC2 or SOS-CIS(D0) ones. C1 [Gan, Zhengting; Shao, Yihan; Kong, Jing] Q Chem Inc, Pittsburgh, PA 15213 USA. [Liu, Fenglai; Yu, Jian-Guo] Beijing Normal Univ, Coll Chem, Beijing 100875, Peoples R China. [Liu, Fenglai; Furlani, Thomas R.; Kong, Jing] SUNY Buffalo, Ctr Computat Res, Buffalo, NY 14260 USA. [Shao, Yihan; Miller, Benjamin T.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Hsu, Chao-Ping] Acad Sinica, Inst Chem, Taipei 115, Taiwan. [Dreuw, Andreas] Goethe Univ Frankfurt, Inst Phys & Theoret Chem, D-60439 Frankfurt, Germany. [Head-Gordon, Martin] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Chem Sci, Berkeley, CA 94720 USA. [Head-Gordon, Martin] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. RP Shao, YH (reprint author), Q Chem Inc, Pittsburgh, PA 15213 USA. EM yihan.shao@gmail.com; jkong@q-chem.com RI Hsu, Chao-Ping/E-1303-2011; Fachbereich14, Dekanat/C-8553-2015; OI Hsu, Chao-Ping/0000-0002-7187-427X; Miller, Benjamin/0000-0003-1647-0122 NR 34 TC 30 Z9 30 U1 1 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0026-8976 J9 MOL PHYS JI Mol. Phys. PY 2010 VL 108 IS 19-20 SI SI BP 2791 EP 2800 AR PII 929126725 DI 10.1080/00268976.2010.526642 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 675YQ UT WOS:000283877300034 ER PT J AU Jayanthi, S Buie, S Moore, S Herning, RI Better, W Wilson, NM Contoreggi, C Cadet, JL AF Jayanthi, S. Buie, S. Moore, S. Herning, R. I. Better, W. Wilson, N. M. Contoreggi, C. Cadet, J. L. TI Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses SO MOLECULAR PSYCHIATRY LA English DT Article DE cannabis; apolipoproteins; protein profiling; cerebrovascular and cardiovascular risk factors ID LOW-DENSITY LIPOPROTEINS; CHOLESTEROL-METABOLISM; OVERWEIGHT PATIENTS; ALZHEIMERS-DISEASE; MARIHUANA SMOKING; MASS-SPECTROMETRY; PROSTATE-CANCER; ANGINA-PECTORIS; RISK-FACTORS; CANNABIS AB Marijuana (MJ) is the most commonly used illicit drug in the United States. Its abuse is associated with cognitive dysfunctions and increased resistance to blood flow in the cerebral vasculature. In addition, MJ abuse is associated with increased risks of potentially serious cardiovascular disorders. In the present study, we used the protein chip platform based on surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to test the possibility that MJ abuse might be associated with changes in serum protein levels. Indeed, MJ users showed significant increases in three protein peaks, which were identified as three isoforms of apolipoprotein (apo) C-III. Immunoprecipitation using an apoC-III antibody also validated the identification of the proteins. Marijuana-induced increases in apoC-III levels might occur through chronic stimulation of hepatic cannabinoid receptors (CB1 and/or CB2) by its active ingredient, Delta(9)tetrahydrocannibol (THC). Thus, chronic MJ abuse might cause increased transcription and/or translation of apoC-III in the liver with corresponding changes reflected in the plasma of these patients. In any case, because apoC-III is a cardiovascular risk factor, the increased levels observed in MJ users might explain, in part, the cardiac and cerebral abnormalities reported in these patients. Molecular Psychiatry (2010) 15, 101-112; doi: 10.1038/mp.2008.50; published online 13 May 2008 C1 [Cadet, J. L.] NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Contoreggi, C.] NIDA, Off Clin Director, Intramural Res Program, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Moore, S.] Ciphergen Biosyst, Fremont, CA USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov FU Intramural Research Program of the NIH, NIDA FX This research was supported by the Intramural Research Program of the NIH, NIDA. NR 68 TC 4 Z9 4 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2010 VL 15 IS 1 BP 101 EP 112 DI 10.1038/mp.2008.50 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 535SZ UT WOS:000272992600016 PM 18475272 ER PT J AU Chandler, RJ Venditti, CP AF Chandler, Randy J. Venditti, Charles P. TI Long-term Rescue of a Lethal Murine Model of Methylmalonic Acidemia Using Adeno-associated Viral Gene Therapy SO MOLECULAR THERAPY LA English DT Article ID LIVER-KIDNEY TRANSPLANTATION; COA MUTASE DEFICIENCY; SKELETAL-MUSCLE; MOUSE-LIVER; MANAGEMENT; VECTORS; MICE; PROPIONATE; DISORDERS; SEROTYPES AB Methylmalonic acidemia (MMA) is an organic acidemia caused by deficient activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). This disorder is associated with lethal metabolic instability and carries a poor prognosis for long-term survival. A murine model of MMA that replicates a severe clinical phenotype was used to examine the efficacy of recombinant adeno-associated virus (rAAV) serotype 8 gene therapy as a treatment for MMA. Lifespan extension, body weight, circulating metabolites, transgene expression, and whole animal propionate oxidation were examined as outcome parameters after gene therapy. One-hundred percent of the untreated Mut(-/-) mice (n = 58) died by day of life (DOL) 72, whereas >95% of the adeno-associated virus-treated Mut(-/-) mice (n = 27) have survived for >= 1 year. Despite a gradual loss of transgene expression and elevated circulating metabolites in the treated Mut(-/-) mice, the animals are indistinguishable from unaffected control littermates in size and activity levels. These experiments provide the first definitive evidence that gene therapy will have clinical utility in the treatment of MMA and support the development of gene therapy for other organic acidemias. C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20893 USA. [Chandler, Randy J.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A18,MSC 4442, Bethesda, MD 20893 USA. EM venditti@mail.nih.gov FU National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH) FX The Intramural Research Program of the National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH) supported this research. We thank Christelle Samen; Chenghua Yang and Irene Ginty (NHGRI/ NIH) for the care and veterinary support of the mice; David M. Bodine, IV for providing a critical reading of the manuscript; and University of Pennsylvania, Vector Core for AAV preps and advice. Neal Oden (The EMMES Corporation, Rockville, MD) assisted with statistical analyses. NR 38 TC 18 Z9 18 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2010 VL 18 IS 1 BP 11 EP 16 DI 10.1038/mt.2009.247 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 554PP UT WOS:000274447200005 PM 19861951 ER PT J AU Wu, ZJ Yang, HY Colosi, P AF Wu, Zhijian Yang, Hongyan Colosi, Peter TI Effect of Genome Size on AAV Vector Packaging SO MOLECULAR THERAPY LA English DT Article ID ADENOASSOCIATED VIRAL VECTORS; LEBERS CONGENITAL AMAUROSIS; GENE-THERAPY; IN-VIVO; VIRUS; CAPACITY; TRANSDUCTION; SEROTYPES; PROTEINS; MOUSE AB Adeno-associated virus (AAV) vector genomes have been limited to 5 kilobases (kb) in length because their packaging limit was thought to be similar to the size of the parent AAV genome. Recent reports claim that significantly larger vector genomes can be packaged intact. We examined the packaged vector genomes from plasmid-encoded AAV vectors that ranged from 4.7 to 8.7 kb in length, using AAV types 2, 5, and 8 capsids. Southern blot analysis indicated that packaged AAV vector genomes never exceeded 5.2 kb in length irrespective of the size of the plasmid-encoded vector or the capsid type. This result was confirmed by vector genome probing with strand-specific oligonucleotides. The packaged vector genomes derived from plasmid-encoded vectors exceeding 5 kb were heterogeneous in length and truncated on the 5' end. Despite their truncated genomes, vector preparations produced from plasmid-encoded vectors exceeding 5.2 kb mediated reporter gene expression in vitro at high multiplicity of infection (MOI). The efficiency of expression was substantially lower than that of reporter vectors with genomes <5 kb in length. We propose that transcriptionally functional, intact vector genomes are generated in cells transduced at high MOI from the fragmentary genomes of these larger vectors, probably by recombination. C1 [Wu, Zhijian; Yang, Hongyan; Colosi, Peter] NEI, Ocular Gene Therapy Lab, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. RP Colosi, P (reprint author), NEI, Ocular Gene Therapy Lab, Neurobiol Neurodegenerat & Repair Lab, NIH, 6 Ctr Dr,Room 331B,MSC 0610, Bethesda, MD 20892 USA. EM colosip@nei.nih.gov NR 20 TC 145 Z9 148 U1 5 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2010 VL 18 IS 1 BP 80 EP 86 DI 10.1038/mt.2009.255 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 554PP UT WOS:000274447200013 PM 19904234 ER PT B AU Widemann, B AF Widemann, Brigitte BE Houghton, PJ Arceci, RJ TI Development of Targeted Therapies for Neurofibromatosis Type 1 (NF1) Related Tumors SO MOLECULARLY TARGETED THERAPY FOR CHILDHOOD CANCER LA English DT Article; Book Chapter ID NERVE SHEATH TUMORS; GROWTH-FACTOR RECEPTOR; PHASE-I TRIAL; REFRACTORY SOLID TUMORS; OPTIC PATHWAY GLIOMAS; NF1(+/-) MAST-CELLS; HUMAN SCHWANN-CELLS; PLEXIFORM NEUROFIBROMAS; MAMMALIAN TARGET; MOUSE MODELS C1 NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Widemann, B (reprint author), NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, 10 Ctr Dr,10 CRC,Room 1-5750,MSC 1101, Bethesda, MD 20892 USA. EM widemanb@mail.nih.gov NR 102 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-69060-5 PY 2010 BP 331 EP 350 DI 10.1007/978-0-387-69062-9_16 D2 10.1007/978-0-387-69062-9 PG 20 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BQX55 UT WOS:000282063800016 ER PT J AU Heyd, D Miller, FG AF Heyd, David Miller, Franklin G. TI LIFE PLANS: Do THEY GIVE MEANING TO OUR LIVES? SO MONIST LA English DT Article C1 [Heyd, David] Hebrew Univ Jerusalem, IL-91905 Jerusalem, Israel. [Miller, Franklin G.] NIH, Washington, DC USA. RP Heyd, D (reprint author), Hebrew Univ Jerusalem, IL-91905 Jerusalem, Israel. NR 21 TC 3 Z9 3 U1 0 U2 0 PU HEGELER INST PI PERU PA C/O SHERWOOD J B SUGDEN, 315 FIFTH ST, PERU, IL 61354 USA SN 0026-9662 EI 2153-3601 J9 MONIST JI Monist PD JAN PY 2010 VL 93 IS 1 BP 17 EP 37 PG 21 WC Philosophy SC Philosophy GA V35MK UT WOS:000209153300002 ER PT J AU Cookson, MR AF Cookson, Mark R. TI DJ-1, PINK1, and Their Effects on Mitochondrial Pathways SO MOVEMENT DISORDERS LA English DT Article; Proceedings Paper CT Symposium on Frontiers of Science and Clinical Advances in Quality of Life in Parkinsons Disease CY OCT 11-12, 2007 CL ELECTR NETWORK SP Parkinsons Dis Fdn DE parkinsonism; genetics; PINK1; parkin; DJ-1 ID ONSET PARKINSONS-DISEASE; OXIDATIVE STRESS; ANDROGEN RECEPTOR; CELL-DEATH; ALPHA-SYNUCLEIN; HETEROZYGOUS MUTATIONS; RECESSIVE PARKINSONISM; TRANSCRIPTION ACTIVITY; DOPAMINERGIC-NEURONS; DJ-1-DEFICIENT MICE AB Genetic forms of parkinsonism are interesting for two particular reasons. First, finding a gene identifies a cause for a disease that would otherwise be unexplained. Second, finding several genes for the same disorder allows us to reconstruct molecular pathways that, in the example of Parkinson's disease, are be associated with the survival of dopamine neurons in the substantia nigra. Two rare causes of parkinsonism. DJ-1 and PINK1, are associated with mitochondria. This organelle has long been linked with Parkinson's disease, and recent results are starting to show how mutations impact mitochondrial function. In this short review, I will discuss how we can use some of this information to understand why it is that neurons become dysfunctional in PD. (C) 2010 Movement Disorder Society C1 NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bethesda, MD 20982 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20982 USA. EM cookson@mail.nih.gov FU Intramural NIH HHS [Z01 AG000940-01] NR 77 TC 39 Z9 40 U1 0 U2 7 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. PY 2010 VL 25 IS 3 SU S BP S44 EP S48 DI 10.1002/mds.22713 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 576IE UT WOS:000276137000008 PM 20187230 ER PT S AU Siengthai, S AF Siengthai, Sununta BE Siengthai, S Lawler, JJ Rowley, C Suzuki, H TI GLOBALIZATION AND INDUSTRIAL RELATIONS IN THAILAND SO MULTI-DIMENSIONS OF INDUSTRIAL RELATIONS IN THE ASIAN KNOWLEDGE-BASED ECONOMIES SE Chandos Asian Studies Series-Contemporary Issues and Trends LA English DT Article; Book Chapter C1 [Siengthai, Sununta] Asian Inst Technol, Sch Management, Pathum Thani, Thailand. [Siengthai, Sununta] NIDA, Bethesda, MD USA. [Siengthai, Sununta] Thammasat Univ, Pathum Thani, Thailand. [Siengthai, Sununta] Inst Southeast Asian Studies ISEAS, Singapore, Singapore. [Siengthai, Sununta] Kyoto Inst Econ Res, Kyoto, Japan. [Siengthai, Sununta] Univ N Carolina, Kenan Inst Private Enterprise, Chapel Hill, NC USA. [Siengthai, Sununta] Univ Michigan, Fulbright Senior Visiting Program, Ann Arbor, MI 48109 USA. [Siengthai, Sununta] UNDP, New York, NY USA. RP Siengthai, S (reprint author), Asian Inst Technol, Sch Management, Pathum Thani, Thailand. OI SIENGTHAI, SUNUNTA/0000-0001-6279-9557 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHANDOS PUBL PI SAWSTON PA 80 HIGH ST, SAWSTON, CAMBRIDGE CB22 3HJ, ENGLAND SN 2052-2126 BN 978-1-78063-243-8; 978-1-84334-264-9 J9 CHANDOS ASIAN STUD PY 2010 BP 141 EP 172 D2 10.1533/9781780632438 PG 32 WC Economics; Industrial Relations & Labor; Asian Studies SC Business & Economics; Asian Studies GA BB2FF UT WOS:000341717100007 ER PT S AU Siengthai, S Lawler, JJ Rowley, C Suzuki, H AF Siengthai, Sununta Lawler, John J. Rowley, Chris Suzuki, Hiromasa BE Siengthai, S Lawler, JJ Rowley, C Suzuki, H TI MAKING INDUSTRIAL RELATIONS WORK IN THE GLOBALIZATION ERA: CHALLENGES AHEAD FOR KNOWLEDGE-BASED ECONOMIES SO MULTI-DIMENSIONS OF INDUSTRIAL RELATIONS IN THE ASIAN KNOWLEDGE-BASED ECONOMIES SE Chandos Asian Studies Series-Contemporary Issues and Trends LA English DT Article; Book Chapter C1 [Siengthai, Sununta] Asian Inst Technol, Sch Management, Pathum Thani, Thailand. [Siengthai, Sununta] NIDA, Bethesda, MD USA. [Siengthai, Sununta] Thammasat Univ, Pathum Thani, Thailand. [Siengthai, Sununta] Inst Southeast Asian Studies ISEAS, Singapore, Singapore. [Siengthai, Sununta] Kyoto Inst Econ Res, Kyoto, Japan. [Siengthai, Sununta] Univ N Carolina, Kenan Inst Private Enterprise, Chapel Hill, NC USA. [Siengthai, Sununta] Univ Michigan, Fulbright Senior Visiting Program, Ann Arbor, MI 48109 USA. [Siengthai, Sununta; Suzuki, Hiromasa] ILO, Geneva, Switzerland. [Siengthai, Sununta] UNDP, New York, NY USA. [Siengthai, Sununta] JICA, Osaka, Japan. [Rowley, Chris] Cardiff Business Sch, Cardiff, S Glam, Wales. [Rowley, Chris] Univ London, London WC1E 7HU, England. [Suzuki, Hiromasa] Waseda Univ, Fac Commerce, Tokyo, Japan. [Suzuki, Hiromasa] Colorado Coll, Colorado Springs, CO 80903 USA. [Suzuki, Hiromasa] CNRS, F-75700 Paris, France. [Suzuki, Hiromasa] ESAN Business Sch, Lima, Peru. [Suzuki, Hiromasa] Japan Inst Labor Policy & Training, Tokyo, Japan. RP Siengthai, S (reprint author), Asian Inst Technol, Sch Management, Pathum Thani, Thailand. OI SIENGTHAI, SUNUNTA/0000-0001-6279-9557 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHANDOS PUBL PI SAWSTON PA 80 HIGH ST, SAWSTON, CAMBRIDGE CB22 3HJ, ENGLAND SN 2052-2126 BN 978-1-78063-243-8; 978-1-84334-264-9 J9 CHANDOS ASIAN STUD PY 2010 BP 215 EP 226 D2 10.1533/9781780632438 PG 12 WC Economics; Industrial Relations & Labor; Asian Studies SC Business & Economics; Asian Studies GA BB2FF UT WOS:000341717100009 ER PT S AU Gillet, JP Gottesman, MM AF Gillet, Jean-Pierre Gottesman, Michael M. BE Zhou, J TI Mechanisms of Multidrug Resistance in Cancer SO MULTI-DRUG RESISTANCE IN CANCER SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Multidrug resistance; Uptake transport; ABC transporters; Drug metabolism; DNA repair; Vaults; Microenvironment; Translational research ID ACUTE MYELOID-LEUKEMIA; MAJOR VAULT PROTEIN; CELL LUNG-CANCER; BINDING CASSETTE TRANSPORTERS; ACUTE LYMPHOBLASTIC-LEUKEMIA; OVARIAN-CARCINOMA CELLS; ADVANCED BREAST-CANCER; INTERSTITIAL FLUID PRESSURE; PLATINUM-BASED CHEMOTHERAPY; DRUG-METABOLIZING-ENZYMES AB The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the Current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis oil ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with Success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram. C1 [Gillet, Jean-Pierre; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gillet, JP (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 253 TC 210 Z9 232 U1 3 U2 29 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-415-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 596 BP 47 EP 76 DI 10.1007/978-1-60761-416-6_4 D2 10.1007/978-1-60761-416-6 PG 30 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BMP86 UT WOS:000273302300004 PM 19949920 ER PT S AU Calcagno, AM Ambudkar, SV AF Calcagno, Anna Maria Ambudkar, Suresh V. BE Zhou, J TI Molecular Mechanisms of Drug Resistance in Single-Step and Multi-Step Drug-Selected Cancer Cells SO MULTI-DRUG RESISTANCE IN CANCER SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Multidrug resistance; Multi-step selection; Single-step selection; ABC transporter; Gene amplification; Epigenetic changes ID KB CARCINOMA-CELLS; ABC TRANSPORTER SUPERFAMILY; MULTIDRUG-RESISTANCE; HUMAN SARCOMA; P-GLYCOPROTEIN; UNTRANSLATED REGION; GENE AMPLIFICATION; CROSS-RESISTANCE; MESSENGER-RNA; MDR1 GENE AB Multidrug resistance (MDR) remains one of the key determinants in chemotherapeutic Success of cancer patients. Often, acquired resistance is mediated by the overexpression of ATP-binding cassette (ABC) drug transporters. To study the mechanisms involved in the MDR phenotype, investigators have generated a variety of in vitro cell Culture models using both multi-step and single-step drug selections. Sublines produced from multi-step selections have led to the discovery of several crucial drug transporters including ABCB1, ABCC1, and ABCG2. Additionally, number of mechanisms causing gene overexpression have been elucidated. To more closely mimic in vivo conditions, investigators have also established MDR sublines with single-step drug selections. Here, we examine some of the multi-step and single-step selected cell lines generated to elucidate the mechanisms involved in the development of MDR in cancer cells. C1 [Calcagno, Anna Maria; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Calcagno, AM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bldg 37, Bethesda, MD 20892 USA. RI Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU Intramural NIH HHS [Z01 BC010030-12] NR 64 TC 16 Z9 16 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-415-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 596 BP 77 EP 93 DI 10.1007/978-1-60761-416-6_5 D2 10.1007/978-1-60761-416-6 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BMP86 UT WOS:000273302300005 PM 19949921 ER PT S AU Aszalos, A Taylor, BJ AF Aszalos, Adorjan Taylor, Barbara J. BE Zhou, J TI Flow Cytometric Evaluation of Multidrug Resistance Proteins SO MULTI-DRUG RESISTANCE IN CANCER SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Transport proteins; P-glycoprotein; Multidrug resistance protein; Breast cancer resistance protein; Flow cytometer ID ACUTE MYELOID-LEUKEMIA; P-GLYCOPROTEIN; LUNG-CANCER; ABC FAMILY; EXPRESSION; CELLS; MRP1; TRANSPORTER; INTESTINE; VARIANTS AB There are several ways to detect proteins on cells. One quite frequently used method is flow cytometry. This method needs fluorescently labeled antibodies that can attach selectively to the protein to be investigated for flow cytometric detection. Flow cytometry scans individual cells, virtually without their surrounding liquid, and can scan many cells in a very short time. Because of this advantage of flow cytometry, it was adapted to investigate transport proteins on normal and cancerous human cells and cell lines. These transport proteins play important roles in human metabolism. Absorption in the intestine, excretion at the kidney, protection of the CNS compartment and the fetus from xenobiotics, and other vital functions depend on these transporters. However, several transporters are overexpressed in cancer cells. These overexpressed transporters pump out anticancer drugs from the cells and prevent their curative effects. The detection and quantitation of these types of transporters in cancer cells is important for this reason. Here, we review literature on flow cytometric detection of the three most studied transporters: P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance protein. C1 [Aszalos, Adorjan] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Taylor, Barbara J.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Aszalos, A (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 32 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-415-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 596 BP 123 EP 139 DI 10.1007/978-1-60761-416-6_7 D2 10.1007/978-1-60761-416-6 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BMP86 UT WOS:000273302300007 PM 19949923 ER PT S AU Dmitrienko, A Bretz, F Westfall, PH Troendle, J Wiens, BL Tamhane, AC Hsu, JC AF Dmitrienko, Alex Bretz, Frank Westfall, Peter H. Troendle, James Wiens, Brian L. Tamhane, Ajit C. Hsu, Jason C. BE Dmitrienko, A Tamhane, AC Bretz, F TI Multiple Testing Methodology SO MULTIPLE TESTING PROBLEMS IN PHARMACEUTICAL STATISTICS SE Chapman & Hall-CRC Biostatistics Series LA English DT Article; Book Chapter C1 [Dmitrienko, Alex] Eli Lilly & Co, Global Stat Sci, Indianapolis, IN 46285 USA. [Bretz, Frank] Novartis, Basel, Switzerland. [Westfall, Peter H.] Texas Tech Univ, Informat Syst & Quantitat Sci, Lubbock, TX 79409 USA. [Troendle, James] NIH, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Wiens, Brian L.] Alcon Labs Inc, Dev, Ft Worth, TX 76101 USA. [Tamhane, Ajit C.] Northwestern Univ, Robert R McCormick Sch Engn & Appl Sci, IEMS, Evanston, IL 60208 USA. [Hsu, Jason C.] Ohio State Univ, Dept Stat, Columbus, OH 43210 USA. RP Dmitrienko, A (reprint author), Eli Lilly & Co, Global Stat Sci, Indianapolis, IN 46285 USA. RI Tamhane, Ajit/B-7495-2009 NR 0 TC 4 Z9 4 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-4298 BN 978-1-58488-985-4; 978-1-58488-984-7 J9 CH CRC BIOSTAT SER JI Chapman & Hall-CRC Biostat. Ser. PY 2010 VL 33 BP 35 EP 98 PG 64 WC Mathematical & Computational Biology; Pharmacology & Pharmacy SC Mathematical & Computational Biology; Pharmacology & Pharmacy GA BD7JF UT WOS:000363208600003 ER PT J AU Liu, G Swierczewska, M Lee, S Chen, XY AF Liu, Gang Swierczewska, Magdalena Lee, Seulki Chen, Xiaoyuan TI Functional nanoparticles for molecular imaging guided gene delivery SO NANO TODAY LA English DT Review DE Gene delivery; Imaging probes; Image-guided gene; therapy; Molecular imaging; Nanoparticles ID IRON-OXIDE NANOPARTICLES; WALLED CARBON NANOTUBES; SMALL-INTERFERING RNA; MODIFIED SILICA NANOPARTICLES; RESONANCE ENERGY-TRANSFER; IN-VIVO; PLASMID DNA; SIRNA DELIVERY; QUANTUM DOTS; GOLD NANOPARTICLES AB Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized. (C) 2010 Published by Elsevier Ltd. C1 [Liu, Gang; Swierczewska, Magdalena; Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Liu, Gang] N Sichuan Med Coll, Dept Radiol, Sichuan Key Lab Med Imaging, Nanchong 637007, Peoples R China. [Swierczewska, Magdalena] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM Seulki.Lee@nih.gov; Shawn.Chen@nih.gov FU National Institutes of Biomedical Imaging and Bioengineering (NIBIB), NIH; NSFC [30973662]; National Institute of Standards and Technology (NIST) FX This work was supported by the Intramural Research Program (IRP) of the National Institutes of Biomedical Imaging and Bioengineering (NIBIB), NIH. G.L. acknowledges the support from NSFC under grant No. 30973662. S.L. acknowledges a National Research Council Research Associateship Award funded by the National Institute of Standards and Technology (NIST) and the IRP of NIBIB, NIH. NR 135 TC 76 Z9 78 U1 3 U2 45 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1748-0132 EI 1878-044X J9 NANO TODAY JI Nano Today PY 2010 VL 5 IS 6 BP 524 EP 539 DI 10.1016/j.nantod.2010.10.005 PG 16 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 701YU UT WOS:000285861900007 PM 22473061 ER PT B AU Kozak, CA AF Kozak, Christine A. BE St Georgiev, V Zoon, KC TI The Evolution of Gammaretrovirus Restriction Factors in the Mouse SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID MURINE LEUKEMIA-VIRUS; CELL-SURFACE RECEPTOR; HOST-RANGE RESTRICTIONS; FOCUS-INDUCING VIRUSES; MAJOR HOMOLOGY REGION; SPECIES MUS-CASTANEUS; WILD-DERIVED MICE; MUTATIONAL ANALYSIS; POSITIVE SELECTION; ENVELOPE GENES C1 NIAID, Mol Microbiol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 71 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 3 EP 11 DI 10.1007/978-1-60761-512-5_1 D2 10.1007/978-1-60761-512-5 PG 9 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800001 ER PT B AU Cohen, JI AF Cohen, Jeffrey I. BE St Georgiev, V Zoon, KC TI Herpesvirus Research at the National Institute of Allergy and Infectious Diseases: Thirty Years of Progress SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID EPSTEIN-BARR-VIRUS; LATENCY-ASSOCIATED PROTEIN; RECURRING GENITAL HERPES; PLACEBO-CONTROLLED TRIAL; HUMAN TRIGEMINAL GANGLIA; SIMPLEX-VIRUS; VARICELLA-ZOSTER; RECOMBINANT GLYCOPROTEIN; ORAL ACYCLOVIR; GUINEA-PIGS C1 NIAID, Med Virol Sect, Lab Clin Infect Dis, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Dis, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 59 TC 9 Z9 9 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 13 EP 25 DI 10.1007/978-1-60761-512-5_2 D2 10.1007/978-1-60761-512-5 PG 13 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800002 ER PT B AU Hasenkrug, KJ AF Hasenkrug, Kim J. BE St Georgiev, V Zoon, KC TI Why Study Mouse Retroviruses? SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease-Series LA English DT Article; Book Chapter ID REGULATORY T-CELLS; HIV-INFECTED INDIVIDUALS; VIRUS-INDUCED ERYTHROLEUKEMIA; IMMUNOLOGICAL SELF-TOLERANCE; FRIEND MURINE RETROVIRUS; IN-VITRO; SPONTANEOUS-RECOVERY; GAMMA-INTERFERON; SURFACE ANTIGENS; RESISTANCE GENE C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Div Intramural Res,NIH, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Div Intramural Res,NIH, Hamilton, MT 59840 USA. NR 38 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 978-1-60761-511-8 J9 INFECT DIS-SER PY 2010 BP 27 EP 30 DI 10.1007/978-1-60761-512-5_3 D2 10.1007/978-1-60761-512-5 PG 4 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800003 ER PT B AU Guglielmi, KM Patton, JT AF Guglielmi, Kristen M. Patton, John T. BE St Georgiev, V Zoon, KC TI Functions of the Rotavirus RNA Polymerase in Virus Replication SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID DOUBLE-STRANDED-RNA; BINDING PROTEIN NS35; CELL-FREE SYSTEM; GENOME REPLICATION; MESSENGER-RNA; IN-VITRO; GUANYLYLTRANSFERASE ACTIVITY; MOLECULAR CHARACTERIZATION; 3-DIMENSIONAL STRUCTURE; SIMIAN ROTAVIRUS-SA11 C1 [Guglielmi, Kristen M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Guglielmi, KM (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014 NR 77 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 31 EP 40 DI 10.1007/978-1-60761-512-5_4 D2 10.1007/978-1-60761-512-5 PG 10 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800004 ER PT B AU Yasunaga, J Jeang, KT AF Yasunaga, Junichiro Jeang, Kuan-Teh BE St Georgiev, V Zoon, KC TI Human T-Cell Leukemia Virus Type 1, Cellular Transformation, and Adult T-Cell Leukemia SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID HTLV-I TAX; NF-KAPPA-B; TUMOR-SUPPRESSOR PROTEIN; TRANSGENIC MOUSE MODEL; TRANSCRIPTIONAL ACTIVITY; HUMAN-LYMPHOCYTES; P12(I) PROTEIN; RETINOBLASTOMA PROTEIN; PHYSICAL INTERACTION; SPINDLE CHECKPOINT C1 [Yasunaga, Junichiro; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Yasunaga, J (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 93 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 41 EP 49 DI 10.1007/978-1-60761-512-5_5 D2 10.1007/978-1-60761-512-5 PG 9 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800005 ER PT B AU Murphy, PM AF Murphy, Philip M. BE St Georgiev, V Zoon, KC TI Roles for Chemokine Receptors in HIV Pathogenesis SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID NILE-VIRUS-INFECTION; MIP-1 ALPHA; CCR5; DEFICIENCY; RANTES; RISK; BETA C1 NIAID, Lab Mol Immunol, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 53 EP 57 DI 10.1007/978-1-60761-512-5_6 D2 10.1007/978-1-60761-512-5 PG 5 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800006 ER PT B AU Strebel, K AF Strebel, Klaus BE St Georgiev, V Zoon, KC TI HIV-1 Accessory Proteins: Crucial Elements for Virus-Host Interactions SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID TYPE-1 VPU PROTEIN; SINGLE AMINO-ACID; VIRION INFECTIVITY FACTOR; EDITING ENZYME APOBEC3G; B TRANSCRIPTION FACTORS; VIF PROTEIN; ANTIVIRAL ACTIVITY; REVERSE TRANSCRIPTION; CYTOPLASMIC DOMAIN; KAPPA-B C1 NIAID, Mol Microbiol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 110 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 59 EP 71 DI 10.1007/978-1-60761-512-5_7 D2 10.1007/978-1-60761-512-5 PG 13 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800007 ER PT B AU Omsland, A Gilk, SD Shannon, JG Beare, PA Voth, DE Howe, D Cockrell, DC Heinzen, RA AF Omsland, Anders Gilk, Stacey D. Shannon, Jeffrey G. Beare, Paul A. Voth, Daniel E. Howe, Dale Cockrell, Diane C. Heinzen, Robert A. BE St Georgiev, V Zoon, KC TI Exploring the Cause of Human Q Fever: Recent Advances in Coxiella burnetii Research SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID PARASITOPHOROUS VACUOLE; LEGIONELLA-PNEUMOPHILA; HOST-CELL; CHLAMYDIA-TRACHOMATIS; LYSOSOMAL RESPONSE; EFFECTOR PROTEINS; MATURATION; LIPOPOLYSACCHARIDE; TRANSPOSON; IMMUNITY C1 [Omsland, Anders; Gilk, Stacey D.; Shannon, Jeffrey G.; Beare, Paul A.; Voth, Daniel E.; Howe, Dale; Cockrell, Diane C.; Heinzen, Robert A.] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Div Intramural Res,NIH, Hamilton, MT 59840 USA. RP Omsland, A (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Div Intramural Res,NIH, Hamilton, MT 59840 USA. NR 68 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 75 EP 85 DI 10.1007/978-1-60761-512-5_8 D2 10.1007/978-1-60761-512-5 PG 11 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800008 ER PT B AU Hinnebusch, BJ AF Hinnebusch, B. Joseph BE St Georgiev, V Zoon, KC TI Plague in the 21st Century: Global Public Health Challenges and Goals SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID YERSINIA-PESTIS; BIOFILM FORMATION; BUBONIC PLAGUE; FLEA VECTOR; PNEUMONIC PLAGUE; RAT MODEL; EVOLUTION; TRANSMISSION; PSEUDOTUBERCULOSIS; PHOSPHODIESTERASE C1 NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Div Intramural Res,NIH, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Div Intramural Res,NIH, Hamilton, MT 59840 USA. NR 32 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 87 EP 94 DI 10.1007/978-1-60761-512-5_9 D2 10.1007/978-1-60761-512-5 PG 8 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800009 ER PT B AU Otto, M AF Otto, Michael BE St Georgiev, V Zoon, KC TI Molecular Biology of Staphylococcal Pathogenesis SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID PANTON-VALENTINE LEUKOCIDIN; QUORUM-SENSING SYSTEM; BIOFILM FORMATION; AUREUS PNEUMONIA; GENE-REGULATION; IMMUNE EVASION; EPIDERMIDIS; VIRULENCE; EXPRESSION; EVOLUTION C1 NIAID, Lab Human Bacterial Pathogenesis, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 24 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 95 EP 99 DI 10.1007/978-1-60761-512-5_10 D2 10.1007/978-1-60761-512-5 PG 5 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800010 ER PT B AU Schwan, TG AF Schwan, Tom G. BE St Georgiev, V Zoon, KC TI Investigations of Relapsing Fever at Home and Abroad SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE GLPQ; SPIROCHETE BORRELIA-HERMSII; TICK-BORNE BORRELIOSIS; WEST-AFRICA; NORTH-AMERICA; LYME-DISEASE; CALIFORNIA; TURICATAE C1 NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Div Intramural Res,NIH, Hamilton, MT 59840 USA. RP Schwan, TG (reprint author), NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Div Intramural Res,NIH, Hamilton, MT 59840 USA. NR 53 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 101 EP 106 DI 10.1007/978-1-60761-512-5_11 D2 10.1007/978-1-60761-512-5 PG 6 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800011 ER PT B AU Rosa, PA AF Rosa, Patricia A. BE St Georgiev, V Zoon, KC TI Molecular Sleuthing with the Lyme Disease Agent SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID SPIROCHETE BORRELIA-BURGDORFERI; OUTER-SURFACE PROTEIN; 32-KILOBASE CIRCULAR PLASMIDS; INFECTIOUS CYCLE; MAMMALIAN HOST; TRANSPOSON MUTAGENESIS; LINEAR PLASMIDS; GENE-EXPRESSION; OSPC GENE; SALIVARY-GLANDS C1 NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Div Intramural Res,NIH, Hamilton, MT 59840 USA. RP Rosa, PA (reprint author), NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Div Intramural Res,NIH, Hamilton, MT 59840 USA. NR 72 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 107 EP 115 DI 10.1007/978-1-60761-512-5_12 D2 10.1007/978-1-60761-512-5 PG 9 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800012 ER PT B AU Warawa, JM Gherardini, FC AF Warawa, Jonathan M. Gherardini, Frank C. BE St Georgiev, V Zoon, KC TI Modeling of Acute Respiratory Melioidosis and Glanders SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID BURKHOLDERIA-PSEUDOMALLEI; SURVIVAL C1 [Warawa, Jonathan M.; Gherardini, Frank C.] NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Div Intramural Res,NIH, Hamilton, MT 59840 USA. RP Warawa, JM (reprint author), NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, Div Intramural Res,NIH, Hamilton, MT 59840 USA. NR 14 TC 2 Z9 2 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 117 EP 120 DI 10.1007/978-1-60761-512-5_13 D2 10.1007/978-1-60761-512-5 PG 4 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800013 ER PT B AU Kwon-Chung, KJ Bennett, JE AF Kwon-Chung, K. J. Bennett, John E. BE St Georgiev, V Zoon, KC TI Cryptococcosis: From Discovering the Natural Reservoir of its Etiology to the Genetic Manipulation of Cryptococcus neoformans: Milestones in Cryptococcal Research by Intramural Investigators at NIAID SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID SKIN-TEST ANTIGEN; AMPHOTERICIN-B; VAR GATTII; EPIDEMIOLOGIC DIFFERENCES; ENZYMATIC METHOD; SEX-CHROMOSOMES; MATING TYPES; 2 VARIETIES; SEROTYPE-A; IN-VITRO C1 [Kwon-Chung, K. J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [Bennett, John E.] NIAID, Clin Mycol Sect, Lab Clin Infect Dis, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 98 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 123 EP 134 DI 10.1007/978-1-60761-512-5_14 D2 10.1007/978-1-60761-512-5 PG 12 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800014 ER PT B AU Sher, A Jankovic, D AF Sher, Alan Jankovic, Dragana BE St Georgiev, V Zoon, KC TI Lessons from Parasites on CD4(+) T-Cell Subset Differentiation and Function SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID TOXOPLASMA-GONDII INFECTION; DENDRITIC CELLS; IL-12; RESPONSES; MICE; SCHISTOSOMIASIS; LYMPHOCYTES; ACTIVATION; INDUCTION; PROFILIN C1 [Sher, Alan; Jankovic, Dragana] NIAID, Immunobiol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Sher, A (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 137 EP 142 DI 10.1007/978-1-60761-512-5_15 D2 10.1007/978-1-60761-512-5 PG 6 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800015 ER PT B AU Sacks, D AF Sacks, David BE St Georgiev, V Zoon, KC TI Molecular Aspects of Parasite - Vector Interactions In Leishmaniasis SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID PHLEBOTOMINE SAND FLIES; MAJOR PROMASTIGOTES; SURFACE LIPOPHOSPHOGLYCAN; INFECTIVE STAGE; DEVELOPMENTAL MODIFICATION; METACYCLIC PROMASTIGOTES; FLY INTERACTIONS; EXPRESSION; MIDGUT; IDENTIFICATION C1 NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Sacks, D (reprint author), NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 1 Z9 1 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 143 EP 149 DI 10.1007/978-1-60761-512-5_16 D2 10.1007/978-1-60761-512-5 PG 7 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800016 ER PT B AU Barillas-Mury, CV AF Barillas-Mury, Carolina V. BE St Georgiev, V Zoon, KC TI Mosquito Strategies Against Plasmodium: A Tale of Restrained Response and Immune Evasion SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID VECTOR ANOPHELES-GAMBIAE; MIDGUT CELLS; OOKINETE INVASION; DROSOPHILA; DETERMINANT; NITRATION; GENES; MODEL C1 NIAID, Mosquito Immun & Vector Competence Unit, Lab Malaria & Vector Res, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Barillas-Mury, CV (reprint author), NIAID, Mosquito Immun & Vector Competence Unit, Lab Malaria & Vector Res, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 153 EP 159 DI 10.1007/978-1-60761-512-5_17 D2 10.1007/978-1-60761-512-5 PG 7 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800017 ER PT B AU Desai, SA AF Desai, Sanjay A. BE St Georgiev, V Zoon, KC TI The Plasmodial Surface Anion Channel: A Model Microbial Ion Channel and Target for Antimalarial Drug Development SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID MALARIA-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; CHLOROQUINE RESISTANCE; PERMEABILITY PATHWAYS; CHLORIDE CHANNELS; HOST ERYTHROCYTE; FALCIPARUM; PARASITE; TRANSPORT; DANTROLENE C1 NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 43 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 161 EP 167 DI 10.1007/978-1-60761-512-5_18 D2 10.1007/978-1-60761-512-5 PG 7 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800018 ER PT B AU Su, XZ AF Su, Xin-zhuan BE St Georgiev, V Zoon, KC TI Genomics and Genetics of Drug Resistance and Regulation of Malaria Parasite Development SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID PLASMODIUM-FALCIPARUM GENOME; VIVAX MALARIA; POPULATION-STRUCTURE; ANTIMALARIAL-DRUGS; MIXED INFECTIONS; RECOMBINATION; DIVERSITY; POLYMORPHISMS; CHLOROQUINE; ORIGIN C1 NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 169 EP 175 DI 10.1007/978-1-60761-512-5_19 D2 10.1007/978-1-60761-512-5 PG 7 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800019 ER PT B AU Bosio, CM AF Bosio, Catharine M. BE St Georgiev, V Zoon, KC TI Modulation of Human Dendritic Cells by Highly Virulent Pathogens SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID EBOLA HEMORRHAGIC-FEVER; FRANCISELLA-TULARENSIS; MARBURG VIRUS; ENDOTOXIN TOLERANCE; HUMAN MONOCYTES; INFECTION; TULAREMIA; ACTIVATION; PROTEIN; FILOVIRUS C1 NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT USA. RP Bosio, CM (reprint author), NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT USA. RI Bosio, Catharine/D-7456-2015 NR 54 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 179 EP 183 DI 10.1007/978-1-60761-512-5_20 D2 10.1007/978-1-60761-512-5 PG 5 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800020 ER PT B AU Germain, RN Bajenoff, M Castellino, F Chieppa, M Egen, JG Huang, AYC Ishii, M Koo, LY Qi, H AF Germain, Ronald N. Bajenoff, Marc Castellino, Flora Chieppa, Marcello Egen, Jackson G. Huang, Alex Y. C. Ishii, Masaru Koo, Lily Y. Qi, Hai BE St Georgiev, V Zoon, KC TI Making Friends in Out-of-the-Way Places: How Cells of the Immune System Get Together and How They Conduct Their Business as Revealed by Intravital Imaging SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID CD8(+) T-CELLS; HIGH-ENDOTHELIAL VENULES; LYMPH-NODE CORTEX; BEARING DENDRITIC CELLS; TOLL-LIKE RECEPTOR-5; CLASS-II TRANSPORT; IN-VIVO; B-CELLS; 2-PHOTON MICROSCOPY; ANTIBODY-RESPONSES C1 [Germain, Ronald N.; Chieppa, Marcello; Egen, Jackson G.; Ishii, Masaru; Qi, Hai] NIAID, Immunol Lab, Lymphocyte Biol Sect,Div Intramural Res, Program Syst Immunol & Infect Dis Modeling,NIH, Bethesda, MD 20892 USA. [Bajenoff, Marc] Univ Nice Sophia Antipolis, INSERM, U344, IPMC,CNRS, Valbonne, France. [Castellino, Flora] Novartis Vaccines & Diagnost, Res Ctr, Siena, Italy. [Huang, Alex Y. C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Sch Med, Div Pediat Hematol Oncol, Cleveland, OH 44106 USA. [Koo, Lily Y.] NIAID, Biol Imaging Facil, Res Technol Branch, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Immunol Lab, Lymphocyte Biol Sect,Div Intramural Res, Program Syst Immunol & Infect Dis Modeling,NIH, Bldg 10, Bethesda, MD 20892 USA. NR 111 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 185 EP 202 DI 10.1007/978-1-60761-512-5_21 D2 10.1007/978-1-60761-512-5 PG 18 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800021 ER PT B AU Shevach, EM AF Shevach, Ethan M. BE St Georgiev, V Zoon, KC TI Role of Regulatory/Suppressor T Cells in Immune Responses SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID SUPPRESSOR FUNCTION; CUTTING EDGE; AUTOIMMUNE GASTRITIS; DENDRITIC CELLS; IN-VITRO; RECEPTOR; ACTIVATION; INDUCTION; EXPRESSION; IL-2 C1 NIAID, Cellular Immunol Sect, Immunol Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Cellular Immunol Sect, Immunol Lab, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 24 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 203 EP 213 DI 10.1007/978-1-60761-512-5_22 D2 10.1007/978-1-60761-512-5 PG 11 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800022 ER PT B AU Zheng, LX Lenardo, M AF Zheng, Lixin Lenardo, Michael BE St Georgiev, V Zoon, KC TI Proliferation versus Contraction of Immune Cells, the Non-Apoptotic Role of Caspase 8 In Immune Homeostasis SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID AUTOIMMUNE-LYMPHOPROLIFERATIVE-SYNDROME; FAS LIGAND; PRIMARY IMMUNODEFICIENCY; INACTIVATING MUTATIONS; MEDIATED APOPTOSIS; SIGNALING COMPLEX; T-CELLS; DEATH; ACTIVATION; RECEPTOR C1 [Zheng, Lixin; Lenardo, Michael] NIAID, Immunol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Zheng, LX (reprint author), NIAID, Immunol Lab, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 41 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 215 EP 220 DI 10.1007/978-1-60761-512-5_23 D2 10.1007/978-1-60761-512-5 PG 6 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800023 ER PT B AU Morse, HC Janz, S Qi, CF Shin, DM Davidson, WF Wang, HS Li, ZY Roopenian, DC Hartley, JW Fredrickson, TN Kovalchuk, A Potter, M AF Morse, Herbert C., III Janz, Siegfried Qi, Chen-Feng Shin, Dong-Mi Davidson, Wendy F. Wang, Hongsheng Li, Zhaoyang Roopenian, Derry C. Hartley, Janet W. Fredrickson, Torgny N. Kovalchuk, Alexander Potter, Michael BE St Georgiev, V Zoon, KC TI Features of Plasma Cell-Related Neoplasms in Mice SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID CYTIDINE DEAMINASE AID; ANTI-DNA ANTIBODIES; HUMAN B-CELLS; MARGINAL ZONE; C-MYC; TRANSGENIC MICE; MOUSE PLASMACYTOMAS; B1B CELLS; CHROMOSOMAL TRANSLOCATIONS; MULTIPLE-MYELOMA C1 [Morse, Herbert C., III; Qi, Chen-Feng; Shin, Dong-Mi; Wang, Hongsheng; Li, Zhaoyang; Hartley, Janet W.; Fredrickson, Torgny N.; Kovalchuk, Alexander] NIAID, Immunopathol Lab, Div Intramural Res, NIH, Rockville, MD USA. [Janz, Siegfried] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA USA. [Davidson, Wendy F.] NIAID, Immunol Review Branch, Div Extramural Act, NIH, Rockville, MD USA. [Roopenian, Derry C.] Jackson Lab, Bar Harbor, ME 04609 USA. [Potter, Michael] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, Div Intramural Res, NIH, Rockville, MD USA. NR 87 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 221 EP 230 DI 10.1007/978-1-60761-512-5_24 D2 10.1007/978-1-60761-512-5 PG 10 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800024 ER PT B AU Wang, HS Lee, CH Morse, HC AF Wang, Hongsheng Lee, Chang Hoon Morse, Herbert C., III BE St Georgiev, V Zoon, KC TI A Role of IRF8 in Transcriptional Control of B-Cell Development SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID SEQUENCE-BINDING-PROTEIN; INDUCED CYTIDINE DEAMINASE; COMMON LYMPHOID PROGENITORS; LEUKEMIA-LIKE SYNDROME; MARGINAL-ZONE; BONE-MARROW; GERMINAL CENTER; FACTOR PU.1; KAPPA-B; INTERLEUKIN-7 RECEPTOR C1 [Wang, Hongsheng; Lee, Chang Hoon; Morse, Herbert C., III] NIAID, Immunopathol Lab, Div Intramural Res, NIH, Rockville, MD USA. RP Wang, HS (reprint author), NIAID, Immunopathol Lab, Div Intramural Res, NIH, Rockville, MD USA. NR 123 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 231 EP 241 DI 10.1007/978-1-60761-512-5_25 D2 10.1007/978-1-60761-512-5 PG 11 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800025 ER PT B AU Farber, JM AF Farber, Joshua M. BE St Georgiev, V Zoon, KC TI Laboratory of Molecular Immunology Chemokines in Lymphocyte Biology SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID INFLAMMATORY PROTEIN 3-ALPHA; INTERFERON-INDUCIBLE PROTEIN-10; T-CELL DIFFERENTIATION; NECROSIS IN-VIVO; HUMAN TH17 CELLS; IFN-GAMMA; CXC CHEMOKINE; RHEUMATOID-ARTHRITIS; DENDRITIC CELLS; EXPRESSION CLONING C1 NIAID, Inflammat Biol Sect, Lab Mol Immunol, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAID, Inflammat Biol Sect, Lab Mol Immunol, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 79 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 243 EP 247 DI 10.1007/978-1-60761-512-5_26 D2 10.1007/978-1-60761-512-5 PG 5 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800026 ER PT B AU Sun, PD AF Sun, Peter D. BE St Georgiev, V Zoon, KC TI Structure and Function of Immunoreceptors SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID C-REACTIVE PROTEIN; FC-GAMMA RECEPTOR; LIGAND-BINDING DOMAIN; CRYSTAL-STRUCTURE; DC-SIGN; COMPLEX; RECOGNITION; ANTIGEN; SIALOADHESIN; RESOLUTION C1 NIAID, Immunogenet Lab, Struct Immunol Sect, Div Intramural Res,NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Immunogenet Lab, Struct Immunol Sect, Div Intramural Res,NIH, Rockville, MD 20852 USA. NR 32 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 251 EP 259 DI 10.1007/978-1-60761-512-5_27 D2 10.1007/978-1-60761-512-5 PG 9 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800027 ER PT B AU Burgess, SJ Narayanan, S Borrego, F Coligan, JE AF Burgess, Steven J. Narayanan, Sriram Borrego, Francisco Coligan, John E. BE St Georgiev, V Zoon, KC TI Role of the NKG2D Receptor in Health and Disease SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID MHC CLASS-I; NATURAL-KILLER-CELLS; CD8(+) T-CELLS; CYTOMEGALOVIRUS GLYCOPROTEIN UL16; NK CELLS; DOWN-REGULATION; CUTTING EDGE; TUMOR-CELLS; MEDIATED CYTOTOXICITY; IMMUNE-RESPONSE C1 [Burgess, Steven J.] Pfizer Global Res & Dev, Sandwich CT13 9NJ, Kent, England. [Borrego, Francisco] CDER FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Bethesda, MD USA. NIAID, Receptor Cell Biol Sect, Immunogenet Lab, Div Intramural Res,NIH, Rockville, MD USA. RP Burgess, SJ (reprint author), Pfizer Global Res & Dev, Sandwich CT13 9NJ, Kent, England. NR 150 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 261 EP 273 DI 10.1007/978-1-60761-512-5_28 D2 10.1007/978-1-60761-512-5 PG 13 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800028 ER PT B AU Druey, KM AF Druey, Kirk M. BE St Georgiev, V Zoon, KC TI G-Protein-Evoked Signaling Mechanisms in Asthma and Allergic Disease SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID AIRWAY SMOOTH-MUSCLE; LYMPHOCYTE MIGRATION; BRONCHIAL-ASTHMA; GENE-EXPRESSION; ALPHA-SUBUNITS; T-CELLS; CHEMOKINES; RECEPTORS; RESPONSES; INFLAMMATION C1 NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 47 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 277 EP 281 DI 10.1007/978-1-60761-512-5_29 D2 10.1007/978-1-60761-512-5 PG 5 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800029 ER PT B AU Metcalfe, DD Peavy, RD Gilfillan, AM AF Metcalfe, Dean D. Peavy, Richard D. Gilfillan, Alasdair M. BE St Georgiev, V Zoon, KC TI Mast Cell Precursors and Signaling Pathways SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID FC-EPSILON-RI; GAMMA-RI; C-KIT; PERIPHERAL-BLOOD; PROGENITOR CELLS; IFN-GAMMA; ACTIVATING MUTATION; MEDIATOR RELEASE; GROWTH-FACTOR; UP-REGULATION C1 [Metcalfe, Dean D.; Peavy, Richard D.; Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 60 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 283 EP 295 DI 10.1007/978-1-60761-512-5_30 D2 10.1007/978-1-60761-512-5 PG 13 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800030 ER PT B AU Caughey, B Sim, VL Taubner, LM Wilham, JM Orru, CD Christensen, LB Barton, KL Raymond, GJ Raymond, LD Hughson, AG AF Caughey, Byron Sim, Valerie L. Taubner, Lara M. Wilham, Jason M. Orru, Christina D. Christensen, Leah B. Barton, Kelly L. Raymond, Gregory J. Raymond, Lynne D. Hughson, Andrew G. BE St Georgiev, V Zoon, KC TI Prion Biochemistry and Therapeutics SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID PROTEASE-RESISTANT STATE; CREUTZFELDT-JAKOB-DISEASE; SCRAPIE-ASSOCIATED FORM; CHRONIC WASTING DISEASE; CELL-FREE CONVERSION; IN-VITRO; CYCLIC AMPLIFICATION; SULFATED GLYCANS; PRP ACCUMULATION; STRAIN VARIATION C1 [Caughey, Byron; Sim, Valerie L.; Taubner, Lara M.; Wilham, Jason M.; Orru, Christina D.; Christensen, Leah B.; Barton, Kelly L.; Raymond, Gregory J.; Raymond, Lynne D.; Hughson, Andrew G.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, TSE Prion Biochem Sect,Div Intramural Res,NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, TSE Prion Biochem Sect,Div Intramural Res,NIH, Hamilton, MT 59840 USA. RI Sim, Valerie/C-4137-2013 OI Sim, Valerie/0000-0002-0088-8666 NR 65 TC 0 Z9 0 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 299 EP 303 DI 10.1007/978-1-60761-512-5_31 D2 10.1007/978-1-60761-512-5 PG 5 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800031 ER PT B AU DeLeo, FR AF DeLeo, Frank R. BE St Georgiev, V Zoon, KC TI Neutrophils in the Resolution of Infection SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; APOPTOSIS-DIFFERENTIATION PROGRAM; STAPHYLOCOCCUS-AUREUS INFECTIONS; PANTON-VALENTINE LEUKOCIDIN; BACTERIAL PATHOGENS; GENE-EXPRESSION; HOST-DEFENSE; STREPTOCOCCUS; PHAGOCYTOSIS; DISEASE C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. NR 25 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 305 EP 310 DI 10.1007/978-1-60761-512-5_32 D2 10.1007/978-1-60761-512-5 PG 6 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800032 ER PT B AU Leto, TL Rada, B AF Leto, Thomas L. Rada, Balazs BE St Georgiev, V Zoon, KC TI Reactive Oxidant-Dependent Innate Immune Defenses of the Airway Epithelium: The Dual Oxidase-Lactoperoxidase-Thiocyanate System SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID FAMILY NADPH OXIDASES; HYDROGEN-PEROXIDE; HOST-DEFENSE; NOX-FAMILY; CONGENITAL HYPOTHYROIDISM; CYSTIC-FIBROSIS; ANTIBACTERIAL ACTIVITY; ANTIMICROBIAL SYSTEM; NOX1-DEFICIENT MICE; CHLORIDE CHANNEL C1 [Leto, Thomas L.; Rada, Balazs] NIAID, Mol Defenses Sect, Lab Host Defenses, Div Intramural Res,NIH, Rockville, MD USA. RP Leto, TL (reprint author), NIAID, Mol Defenses Sect, Lab Host Defenses, Div Intramural Res,NIH, Rockville, MD USA. NR 66 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 311 EP 318 DI 10.1007/978-1-60761-512-5_33 D2 10.1007/978-1-60761-512-5 PG 8 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800033 ER PT B AU Zarember, KA Soule, BP Gallin, JI AF Zarember, Kol A. Soule, Benjamin P. Gallin, John I. BE St Georgiev, V Zoon, KC TI Chronic Granulomatous Disease: From Lethal Pediatric Mystery to Complex Chronic Disease SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; RESPIRATORY BURST OXIDASE; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; ADENINE-DINUCLEOTIDE PHOSPHATE; NEUTROPHIL CYTOCHROME-B; RECURRENT BACTERIAL-INFECTIONS; INTERFERON-GAMMA THERAPY; PHAGOCYTE NADPH OXIDASE; BIOLOGICAL DEFENSE-MECHANISMS C1 [Zarember, Kol A.; Soule, Benjamin P.] NIAID, Clin Pathophysiol Sect, Lab Host Defenses, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [Gallin, John I.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Zarember, KA (reprint author), NIAID, Clin Pathophysiol Sect, Lab Host Defenses, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 368 TC 2 Z9 2 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 319 EP 352 DI 10.1007/978-1-60761-512-5_34 D2 10.1007/978-1-60761-512-5 PG 34 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800034 ER PT B AU Rosenberg, HF Domachowske, JB AF Rosenberg, Helene F. Domachowske, Joseph B. BE St Georgiev, V Zoon, KC TI Pneumonia Virus of Mice (PVM): Exploring Novel Therapeutic Options In a Severe Respiratory Disease Model SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID SYNCYTIAL VIRUS; PNEUMOVIRUS INFECTION; INFLAMMATORY RESPONSES; NATURAL HOST; IN-VIVO; SEQUENCE; GENE; BRONCHIOLITIS; PATHOGENESIS; MIP-1-ALPHA C1 [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 43 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 353 EP 359 DI 10.1007/978-1-60761-512-5_35 D2 10.1007/978-1-60761-512-5 PG 7 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800035 ER PT B AU Crampton, SP Bolland, S AF Crampton, Steve P. Bolland, Silvia BE St Georgiev, V Zoon, KC TI Mind Your Xs and Ys: Genetics of the Autoimmune Disease Systemic Lupus Erythematosus SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID FC-GAMMA-RIIB; INOSITOL PHOSPHATASE SHIP; TOLL-LIKE RECEPTORS; ACTIVATE B-CELLS; RESPONSES; AUTOANTIBODIES; PROLIFERATION; AUTOANTIGENS; RECOGNITION; INTERFERON C1 [Crampton, Steve P.; Bolland, Silvia] NIAID, Immunogenet Lab, Div Intramural Res, NIH, Rockville, MD 20852 USA. RP Crampton, SP (reprint author), NIAID, Immunogenet Lab, Div Intramural Res, NIH, Rockville, MD 20852 USA. NR 46 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 371 EP 376 DI 10.1007/978-1-60761-512-5_37 D2 10.1007/978-1-60761-512-5 PG 6 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800037 ER PT B AU Strober, W Fuss, I AF Strober, Warren Fuss, Ivan BE St Georgiev, V Zoon, KC TI A Bench-to-Bedside Trail of Research Leading to the Understanding and Treatment of Ulcerative Colitis SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID INFLAMMATORY-BOWEL-DISEASE; ACTIVE CROHNS-DISEASE; OXAZOLONE COLITIS; CELLS; MICE; NOD2; INDUCTION; ANTIBODIES; RESPONSES; SUBSET C1 [Strober, Warren; Fuss, Ivan] NIAID, Mucosal Immun Sect, Lab Host Defenses, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Lab Host Defenses, Div Intramural Res,NIH, Bethesda, MD 20892 USA. NR 25 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 377 EP 383 DI 10.1007/978-1-60761-512-5_38 D2 10.1007/978-1-60761-512-5 PG 7 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800038 ER PT B AU Kwong, PD Nabel, GJ Acharya, P Boyington, JC Chen, L Hood, C Kim, A Kong, L Do Kwon, Y Majeed, S McLellan, J Ofek, G Pancera, M Sastry, M Changela, A Stuckey, J Zhou, T AF Kwong, Peter D. Nabel, Gary J. Acharya, Priyamvada Boyington, Jeffrey C. Chen, Lei Hood, Chantelle Kim, Albert Kong, Leopold Do Kwon, Young Majeed, Shahzad McLellan, Jason Ofek, Gilad Pancera, Marie Sastry, Mallika Changela, Anita Stuckey, Jonathan Zhou, Tongqing BE St Georgiev, V Zoon, KC TI Structural Biology and the Design of Effective Vaccines for HIV-1 and Other Viruses SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; RESPIRATORY SYNCYTIAL VIRUS; CORECEPTOR BINDING-SITE; AMIDE HYDROGEN-EXCHANGE; PROTEIN CRYSTALLIZATION; RECEPTOR-BINDING; INFLUENZA-VIRUS; MEMBRANE-FUSION C1 [Kwong, Peter D.; Acharya, Priyamvada; Chen, Lei; Kim, Albert; Kong, Leopold; Do Kwon, Young; Majeed, Shahzad; McLellan, Jason; Ofek, Gilad; Pancera, Marie; Sastry, Mallika; Stuckey, Jonathan; Zhou, Tongqing] NIAID, Struct Biol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Nabel, Gary J.; Boyington, Jeffrey C.; Hood, Chantelle] NIAID, Virol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kwong, PD (reprint author), NIAID, Struct Biol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 85 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 387 EP 402 DI 10.1007/978-1-60761-512-5_39 D2 10.1007/978-1-60761-512-5 PG 16 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800039 ER PT B AU Pierce, SK AF Pierce, Susan K. BE St Georgiev, V Zoon, KC TI How Do You Say "B-Cell Biology" In "Vaccinology": Translational Research In the NIAID SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID FC-GAMMA RECEPTORS; ANTIGEN-RECEPTOR; LIVING CELLS; IMMUNITY; MALARIA; DISEASE; PROTEIN; ACTIVATION; INITIATION; GLOBULIN C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 30 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 403 EP 407 DI 10.1007/978-1-60761-512-5_40 D2 10.1007/978-1-60761-512-5 PG 5 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800040 ER PT B AU Wu, YM Ellis, R Miura, K Narum, D Miller, LH AF Wu, Yimin Ellis, Ruth Miura, Kazutoyo Narum, David Miller, Louis H. BE St Georgiev, V Zoon, KC TI Malaria Vaccine Development SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID APICAL MEMBRANE ANTIGEN-1; TRANSMISSION-BLOCKING VACCINE; PLASMODIUM-FALCIPARUM MALARIA; AERUGINOSA EXOPROTEIN-A; PHASE-1 TRIAL; SURFACE; ANTIBODIES; PROTEIN; CANDIDATE; PFS25 C1 [Wu, Yimin; Ellis, Ruth; Miura, Kazutoyo; Narum, David; Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, Div Intramural Res, NIH, Rockville, MD USA. RP Wu, YM (reprint author), NIAID, Malaria Vaccine Dev Branch, Div Intramural Res, NIH, Rockville, MD USA. NR 30 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 409 EP 422 DI 10.1007/978-1-60761-512-5_41 D2 10.1007/978-1-60761-512-5 PG 14 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800041 ER PT B AU Luke, CJ Subbarao, K AF Luke, Catherine J. Subbarao, Kanta BE St Georgiev, V Zoon, KC TI The Development of Live-Attenuated Vaccines for Pandemic Influenza SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID COLD-ADAPTED INFLUENZA; RANDOMIZED CONTROLLED-TRIAL; REASSORTANT VIRUS-VACCINES; CROSS-REACTIVE IMMUNITY; A H5N1 VACCINE; ADULT VOLUNTEERS; DOSE-RESPONSE; AVIAN-HUMAN; TEMPERATURE SENSITIVITY; RECOMBINANT VIRUSES C1 [Luke, Catherine J.; Subbarao, Kanta] NIAID, Infect Dis Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Luke, CJ (reprint author), NIAID, Infect Dis Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 75 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 423 EP 430 DI 10.1007/978-1-60761-512-5_42 D2 10.1007/978-1-60761-512-5 PG 8 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800042 ER PT B AU Valenzuela, JG AF Valenzuela, Jesus G. BE St Georgiev, V Zoon, KC TI Targeting the Messenger: Vector-Based Vaccines to Control Leishmania Infection and Transmission SO NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, NIH, VOL 3: INTRAMURAL RESEARCH SE Infectious Disease LA English DT Article; Book Chapter ID FLY LUTZOMYIA-LONGIPALPIS; MIDGUT TRANSCRIPTOME; SAND FLIES; IDENTIFICATION; PROTECTION; PROTEINS; PATHOGEN; CHAGASI; SALIVA C1 NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 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 978-1-60761-511-8 J9 INFECT DIS PY 2010 BP 431 EP 436 DI 10.1007/978-1-60761-512-5_43 D2 10.1007/978-1-60761-512-5 PG 6 WC Infectious Diseases; Medicine, Research & Experimental SC Infectious Diseases; Research & Experimental Medicine GA BRE92 UT WOS:000282534800043 ER PT S AU Kish, LB Bezrukov, SM Khatril, SP Gingl, Z Sethuraman, S AF Kish, Laszlo B. Bezrukov, S. M. Khatril, S. P. Gingl, Z. Sethuraman, S. BE Peper, F Umeo, H Matsui, N Isokawa, T TI Noise-Based Logic and Computing: From Boolean Logic Gates to Brain Circuitry and Its Possible Hardware Realization SO NATURAL COMPUTING SE Proceedings in Information and Communications Technology LA English DT Proceedings Paper CT 4th International Workshop on Natural Computing (IWNC) CY SEP 23-25, 2009 CL Himeji Int Exchange Ctr, Himeji, JAPAN SP Natl Inst Informat & Commun Technol (NICT), Osaka Elect Commun Univ (OECU), Univ Hyogo (UH), Himeji City, Support Ctr Adv Telecommunicat Technol Res, Soc Instrument & Control Engineers (SICE) HO Himeji Int Exchange Ctr ID SUPERPOSITION; STATES AB When noise dominates an information system, like in nanoelectronic systems of the foreseeable future, a natural question occurs: Can we perhaps utilize the noise as information carrier? Another question is: Can a deterministic logic scheme be constructed that may explain how the brain efficiently processes information, with random neural spike trains of less than 100 Hz frequency, and with a similar number of human brain neurons as the number of transistors in a 16 GB Flash dive? The answers to these questions are yes. Related developments indicate reduced power consumption with noise-based deterministic Boolean logic gates and the more powerful multivalued logic versions with an arbitrary number of logic values. Similar schemes as the Hilbert space of quantum informatics can also be constructed with noise-based logic by utilizing the noise-bits and their multidimensional hyperspace without the limitations of quantum-collapse of wavefunctions. A noise-based string search algorithm faster than Grover's quantum search algorithm can be obtained, with the same hardware complexity class as the quantum engine. This logic hyperspace scheme has also been utilized to construct the noise-based neuro-bits and a deterministic multivalued logic scheme for the brain. Some of the corresponding circuitry of neurons is shown. Some questions and answers about a chip realization of such a random spike based deterministic multivalued logic scheme are presented. C1 [Kish, Laszlo B.; Khatril, S. P.; Sethuraman, S.] Texas A&M Univ, Dept Elect & Comp Engn, College Stn, TX 77845 USA. [Bezrukov, S. M.] NIH, NICHD, Program Phys Biol, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. [Gingl, Z.] Univ Szeged, Dept Expt Phys, H-6720 Szeged, Hungary. RP Kish, LB (reprint author), Texas A&M Univ, Dept Elect & Comp Engn, College Stn, TX 77845 USA. NR 12 TC 2 Z9 2 U1 2 U2 3 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN SN 1867-2914 BN 978-4-431-53867-7 J9 PROC INFO COMMUN PY 2010 VL 2 BP 13 EP + PG 3 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BVJ63 UT WOS:000291667500002 ER PT S AU March, ME Gross, CC Long, EO AF March, Michael E. Gross, Catharina C. Long, Eric O. BE Campbell, KS TI Use of Transfected Drosophila S2 Cells to Study NK Cell Activation SO NATURAL KILLER CELL PROTOCOLS: CELLULAR AND MOLECULAR METHODS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Drosophila; S2; insect cells; NK cells; activation; inhibition; transfection ID NATURAL-KILLER-CELLS; CD8(+) T-CELLS; TARGET-CELLS; MELANOGASTER CELLS; GRANULE POLARIZATION; INHIBITORY RECEPTORS; ADHESION MOLECULES; CYTOTOXICITY; COMPLEX; SPECIFICITY AB Determining the contribution of individual receptors to natural killer (NK) cell function is complicated by the multiplicity of activating and inhibitory NK cell receptors. Mammalian target cells typically express a variety of ligands for NK cell receptors. Engagement of NK cell receptors by antibodies may not mimic activation by natural ligands. To define requirements for activation and dissect the contribution of receptors to NK cell function, we have generated Drosophila Schneider line 2 (S2) cell transfectants expressing ligands for NK cell receptors. The evolutionary distance between Drosophila and mammals greatly reduces the potential of recognition of insect cell molecules by mammalian NK cells. Here, we present methods for maintenance and transfection of S2 cells, as well as protocols for their use in NK cell assays. C1 [March, Michael E.; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP March, ME (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU Intramural NIH HHS [ZIA AI000525-24] NR 37 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-361-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 612 BP 67 EP 88 DI 10.1007/978-1-60761-362-6_6 D2 10.1007/978-1-60761-362-6 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BND74 UT WOS:000274240200006 PM 20033635 ER PT S AU Savan, R Chan, T Young, HA AF Savan, Ram Chan, Tim Young, Howard A. BE Campbell, KS TI Lentiviral Gene Transduction in Human and Mouse NK Cell Lines SO NATURAL KILLER CELL PROTOCOLS: CELLULAR AND MOLECULAR METHODS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Natural killer cells; lentivirus; transduction; flow cytometry; viral titration; human; mouse; NK-92; LNK ID NATURAL-KILLER-CELLS; EFFICIENT; VECTORS; EXPRESSION; DELIVERY; MEDIATE; IL-2; DNA AB Natural killer (NK) cells play a vital role in the control of cancer and microbial infections. A major hinderance in studying NK cells is the resistance of these cells to gene transfer. Considering over-expression and gene knockdown Studies arc crucial tools to study the biology of cells, technologies suitable for transfering genes into NK cells are invaluable. Among various technologies available for gene transfer, lentiviral-mediated transduction has been successful in introducing genes into NK cells. We have standardized methods of lentiviral infection in human and Mouse NK cell lines. We obtain transduction efficiencies of 15% in the NK-92 cell line and 30-40% in LNK, YT, and DERL7 cell lines. This method allows efficient and stable introduction of genes and shRNAs into NK cell lines. C1 [Savan, Ram; Chan, Tim; Young, Howard A.] Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. RP Savan, R (reprint author), Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. FU Intramural NIH HHS NR 20 TC 2 Z9 2 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-361-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 612 BP 209 EP 221 DI 10.1007/978-1-60761-362-6_14 D2 10.1007/978-1-60761-362-6 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BND74 UT WOS:000274240200014 PM 20033643 ER PT S AU Bryceson, YT Fauriat, C Nunes, JM Wood, SM Bjorkstrom, NK Long, EO Ljunggren, HG AF Bryceson, Yenan T. Fauriat, Cyril Nunes, Joao M. Wood, Stephanie M. Bjorkstrom, Niklas K. Long, Eric O. Ljunggren, Hans-Gustaf BE Campbell, KS TI Functional Analysis of Human NK Cells by Flow Cytometry SO NATURAL KILLER CELL PROTOCOLS: CELLULAR AND MOLECULAR METHODS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Human; natural killer cells; immunophenotyping; polychromatic flow cytometry; CD107a; lysosomal-associated membrane protein-1; chemokines; IFN-gamma; MIP-1 beta; TNF-alpha ID NATURAL-KILLER-CELLS; FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; SURFACE EXPRESSION; DEGRANULATION; RECEPTORS; IDENTIFICATION; CD107A AB Natural killer (NK) cells are a Subset of lymphocytes that contribute to innate immunity through cytokine secretion and target cell lysis. NK cell function is regulated by a multiplicity of activating and inhibitory receptors. The advance in instrumentation for multi-color flow cytometry and the generation of specific mAbs for different epitopes related to phenotypic and functional parameters have facilitated Our understanding of NK cell responses. Here, we provide protocols for flow cytometric evaluation of degranulation and cytokine production by human NK cells from peripheral blood at the single-cell level. In addition to offering insight into the regulation of human NK cell responses, these techniques are applicable to the assessment of various clinical conditions, including the diagnosis of immunodeficiency syndromes. C1 [Bryceson, Yenan T.; Fauriat, Cyril; Nunes, Joao M.; Wood, Stephanie M.; Bjorkstrom, Niklas K.; Ljunggren, Hans-Gustaf] Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Ctr Infect Med, Stockholm, Sweden. [Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Bryceson, YT (reprint author), Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Ctr Infect Med, Stockholm, Sweden. RI Wood, Stephanie/D-3528-2012; Long, Eric/G-5475-2011; Fauriat, Cyril/D-4285-2017; OI Wood, Stephanie/0000-0003-4224-759X; Long, Eric/0000-0002-7793-3728; das Eiras Nunes, Joao Manuel/0000-0003-4090-8702; Bjorkstrom, Niklas/0000-0002-0967-076X; Bryceson, Yenan/0000-0002-7783-9934 FU Intramural NIH HHS [ZIA AI000525-22] NR 21 TC 42 Z9 44 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-361-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 612 BP 335 EP 352 DI 10.1007/978-1-60761-362-6_23 D2 10.1007/978-1-60761-362-6 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BND74 UT WOS:000274240200023 PM 20033652 ER PT S AU Kulkarni, S Martin, MP Carrington, M AF Kulkarni, Smita Martin, Maureen P. Carrington, Mary BE Campbell, KS TI KIR Genotyping by Multiplex PCR-SSP SO NATURAL KILLER CELL PROTOCOLS: CELLULAR AND MOLECULAR METHODS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE KIR genotyping; NK cell; KIR haplotypes; multiplex PCR; PCR-SSP ID NK CELL RECOGNITION; DISEASE; GENES; SUSCEPTIBILITY; RECOMBINATION; RECEPTOR; LOCUS AB Diversity across KIR haplotypes sterns from differences in numbers of inhibitory and activating receptors, as well as allelic polymorphism of individual genes. The KIR locus has undergone large expansions and contractions over time and is believed to be coevolving with genes encoding its HLA class I ligands located within the MHC locus. KIR and HLA compound genotypes have been associated with susceptibility to or protection from infectious, autoimmune, reproductive, and malignant disorders. We describe here a simple and reliable multiplex PCR-SSP (sequence-specific priming) method for relatively rapid and inexpensive genotyping of 15 KIR genes using standard agarose gel electrophoresis. C1 [Kulkarni, Smita; Martin, Maureen P.; Carrington, Mary] SAIC Frederick Inc, Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. RP Kulkarni, S (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. FU Intramural NIH HHS [ZIA BC010791-04]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 22 TC 23 Z9 26 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-361-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 612 BP 365 EP 375 DI 10.1007/978-1-60761-362-6_25 D2 10.1007/978-1-60761-362-6 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BND74 UT WOS:000274240200025 PM 20033654 ER PT S AU Li, HC Wright, PW Anderson, SK AF Li, Hongchuan Wright, Paul W. Anderson, Stephen K. BE Campbell, KS TI Identification and Analysis of Novel Transcripts and Promoters in the Human Killer Cell Immunoglobulin-like Receptor (KIR) Genes SO NATURAL KILLER CELL PROTOCOLS: CELLULAR AND MOLECULAR METHODS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE 5 '-RACE; 3 '-RACE; RPA; reporter assays; antisense transcripts ID REPERTOIRE; EXPRESSION; RECOGNITION; MOLECULES; COMPLEX AB This chapter describes the techniques Our lab has used to find the multiple promoters present in individual KIR genes. Our previous Studies in the murine Ly49 gene family led LIS to expect the presence of distal promoters, antisense transcripts, and bi-directional promoters in the KIR gene Cluster. We present here all of the techniques used to systematically determine if a gene possesses these types of control elements. C1 [Li, Hongchuan; Wright, Paul W.; Anderson, Stephen K.] SAIC Frederick Inc, Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. RP Li, HC (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. OI Anderson, Stephen/0000-0002-7856-4266 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 18 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-361-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 612 BP 377 EP 391 DI 10.1007/978-1-60761-362-6_26 D2 10.1007/978-1-60761-362-6 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BND74 UT WOS:000274240200026 PM 20033655 ER PT J AU Subleski, J Weiss, JM Wiltrout, RH Ortaldo, JR AF Subleski, Jeff Weiss, Jonathan M. Wiltrout, Robert H. Ortaldo, John R. BE Lotze, MT Thomson, AW TI NK and NKT cells: the innate-adaptive interface including humoral responses SO NATURAL KILLER CELLS: BASIC SCIENCE AND CLINICAL APPLICATION LA English DT Article; Book Chapter DE NK; NKT; receptors; innate; adaptive; immunity ID NATURAL-KILLER-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; LARGE GRANULAR LYMPHOCYTES; INTERFERON-GAMMA PRODUCTION; INHIBITORY RECEPTOR LY49A; MATERNAL-FETAL INTERFACE; ANTIGEN-PRESENTING CELLS; ACQUIRED IMMUNE-RESPONSE; NONOBESE DIABETIC MICE; CENTRAL-NERVOUS-SYSTEM AB Natural killer (NK) and natural killer T (NKT) cells represent unique lymphoid subsets of the innate immune system that are both critical for some aspects of initiating and directing host adaptive immune responses. These cells share numerous phenotypic markers and functional features, yet are lymphocytes of distinct developmental lineages. As first responders, these innate cells rapidly produce cytokines that modulate various activities of other leukocytes which subsequently influence the ensuing inflammatory response. Moreover, through the expression of effector molecules such as Fas and tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) these cells are capable of directly targeting infected or transformed cells for elimination through cytotoxic pathways. Furthermore, both NK and NKT cells polarize T (helper) cell responses and enhance antigen presentation to cytotoxic T-lymphocytes. C1 [Subleski, Jeff; Weiss, Jonathan M.; Wiltrout, Robert H.; Ortaldo, John R.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. RP Subleski, J (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. NR 237 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 978-0-08-091929-4 PY 2010 BP 255 EP 277 DI 10.1016/B978-0-12-370454-2.00019-3 PG 23 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BFF61 UT WOS:000319666800021 ER PT S AU Newman, DJ Cragg, GM AF Newman, David J. Cragg, Gordon M. BE Buss, AD Butler, MS TI Natural Products as Drugs and Leads to Drugs: The Historical Perspective SO NATURAL PRODUCT CHEMISTRY FOR DRUG DISCOVERY SE RSC Biomolecular Sciences LA English DT Article; Book Chapter ID BETA-LACTAM ANTIBIOTICS; ENDOPHYTIC FUNGUS; CEPHALOSPORIN-C; AMPHOTERICIN-B; DISCOVERY; PODOPHYLLOTOXIN; ECHINOCANDINS; CANDIDIASIS; ENKEPHALIN; BACTERIA C1 [Newman, David J.; Cragg, Gordon M.] NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21701 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, POB B, Frederick, MD 21701 USA. NR 88 TC 10 Z9 10 U1 1 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1757-7152 BN 978-0-85404-193-0 J9 RSC BIOMOL SCI JI RSC Biomol. Sci. PY 2010 IS 18 BP 3 EP 27 PG 25 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMT66 UT WOS:000273554700001 ER PT J AU Giles, KE Ghirlando, R Felsenfeld, G AF Giles, Keith E. Ghirlando, Rodolfo Felsenfeld, Gary TI Maintenance of a constitutive heterochromatin domain in vertebrates by a Dicer-dependent mechanism SO NATURE CELL BIOLOGY LA English DT Article ID BETA-GLOBIN LOCUS; HUMAN-CELLS; RNA INTERFERENCE; GENE; TRANSCRIPTION; INSULATOR AB The 16 kilobase (kb) heterochromatin domain between the chicken beta-globin locus and the folate receptor gene is used here to study the roles of RNA-dependent mechanisms and histone modifications in the maintenance of a constitutive heterochromatic structure. Inhibition of histone deacetylase (HDAC) activity is shown to both increase intergenic transcription and render the heterochromatin more accessible to MspI digestion. We show that short interfering RNA (siRNA)-mediated downregulation of the enzyme Dicer has similar effects: histone acetylation is increased, transcript levels rise and the compact chromatin structure becomes more accessible to restriction endonucleases. We also show that the chicken Argonaute 2 homologue binds the 16 kb region in a Dicer-dependent manner and is necessary for a condensed chromatin structure. Heterochromatic domains of this kind, which are widely distributed in vertebrate genomes, thus seem to be maintained in their condensed form by highly conserved mechanisms. C1 [Giles, Keith E.; Ghirlando, Rodolfo; Felsenfeld, Gary] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov RI Ghirlando, Rodolfo/A-8880-2009 FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the intramural research program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. NR 15 TC 29 Z9 29 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2010 VL 12 IS 1 BP 94 EP U246 DI 10.1038/ncb2010 PG 12 WC Cell Biology SC Cell Biology GA 535MS UT WOS:000272973800018 PM 20010811 ER PT J AU Biesecker, LG AF Biesecker, Leslie G. TI Exome sequencing makes medical genomics a reality SO NATURE GENETICS LA English DT Editorial Material AB Massively parallel sequencing of the exomes of four individuals with Miller syndrome, combined with filtering to exclude benign and unrelated variants, has identified causative mutations in DHODH. This approach will accelerate discovery of the genetic bases of hundreds of other rare mendelian disorders. C1 NHGRI, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov NR 4 TC 86 Z9 92 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JAN PY 2010 VL 42 IS 1 BP 13 EP 14 DI 10.1038/ng0110-13 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 536PA UT WOS:000273055100007 PM 20037612 ER PT J AU Cirstea, IC Kutsche, K Dvorsky, R Gremer, L Carta, C Horn, D Roberts, AE Lepri, F Merbitz-Zahradnik, T Konig, R Kratz, CP Pantaleoni, F Dentici, ML Joshi, VA Kucherlapati, RS Mazzanti, L Mundlos, S Patton, MA Silengo, MC Rossi, C Zampino, G Digilio, C Stuppia, L Seemanova, E Pennacchio, LA Gelb, BD Dallapiccola, B Wittinghofer, A Ahmadian, MR Tartaglia, M Zenker, M AF Cirstea, Ion C. Kutsche, Kerstin Dvorsky, Radovan Gremer, Lothar Carta, Claudio Horn, Denise Roberts, Amy E. Lepri, Francesca Merbitz-Zahradnik, Torsten Koenig, Rainer Kratz, Christian P. Pantaleoni, Francesca Dentici, Maria L. Joshi, Victoria A. Kucherlapati, Raju S. Mazzanti, Laura Mundlos, Stefan Patton, Michael A. Silengo, Margherita Cirillo Rossi, Cesare Zampino, Giuseppe Digilio, Cristina Stuppia, Liborio Seemanova, Eva Pennacchio, Len A. Gelb, Bruce D. Dallapiccola, Bruno Wittinghofer, Alfred Ahmadian, Mohammad R. Tartaglia, Marco Zenker, Martin TI A restricted spectrum of NRAS mutations causes Noonan syndrome SO NATURE GENETICS LA English DT Article ID RAS PROTEINS; DISORDERS; CANCER; SWITCH; KRAS AB Noonan syndrome, a developmental disorder characterized by congenital heart defects, reduced growth, facial dysmorphism and variable cognitive deficits, is caused by constitutional dysregulation of the RAS-MAPK signaling pathway. Here we report that germline NRAS mutations conferring enhanced stimulus-dependent MAPK activation account for some cases of this disorder. These findings provide evidence for an obligate dependency on proper NRAS function in human development and growth. C1 [Wittinghofer, Alfred; Zenker, Martin] Max Planck Inst Mol Physiol, Dept Biol Struct, D-44139 Dortmund, Germany. [Cirstea, Ion C.; Dvorsky, Radovan; Gremer, Lothar; Merbitz-Zahradnik, Torsten; Ahmadian, Mohammad R.] Univ Dusseldorf, Med Ctr, Inst Biochem & Mol Biol 2, Dusseldorf, Germany. [Kutsche, Kerstin] Univ Klinikum Hamburg Eppendorf, Inst Humangenet, Hamburg, Germany. [Carta, Claudio; Pantaleoni, Francesca; Tartaglia, Marco] Ist Super Sanita, Dipartimento Ematol Oncol & Med Mol, I-00161 Rome, Italy. [Horn, Denise; Mundlos, Stefan] Charite, Inst Med Genet, D-13353 Berlin, Germany. [Roberts, Amy E.; Joshi, Victoria A.; Kucherlapati, Raju S.] Harvard Univ, Sch Med, Boston, MA USA. [Roberts, Amy E.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Lepri, Francesca; Dentici, Maria L.; Dallapiccola, Bruno] Ist Ricovero & Cura Carattere Sci Casa Sollievo S, San Giovanni Rotondo, Italy. [Lepri, Francesca; Dentici, Maria L.; Dallapiccola, Bruno] Casa Sollievo Sofferenza Ist Mendel, Rome, Italy. [Koenig, Rainer] Goethe Univ Frankfurt, Inst Human Genet, Frankfurt, Germany. [Kratz, Christian P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Kratz, Christian P.] Univ Freiburg, Dept Paediat & Adolescent Med, Freiburg, Germany. [Joshi, Victoria A.] Partners HealthCare Ctr Personalized Genet Med, Boston, MA USA. [Joshi, Victoria A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mazzanti, Laura] Univ Bologna, Dipartimento Pediat, Bologna, Italy. [Patton, Michael A.] Univ London St Georges Hosp, Dept Clin Genet, London, England. [Silengo, Margherita Cirillo] Univ Turin, Dipartimento Pediat, Turin, Italy. [Rossi, Cesare] St Orsola Marcello Malpighi Hosp, Unita Operat Genet Med, Bologna, Italy. [Zampino, Giuseppe] Univ Cattolica Sacro Cuore, Ist Clin Pediat, Rome, Italy. [Digilio, Cristina] Bambino Gesu Pediat Hosp, Sez Genet Med, Rome, Italy. [Stuppia, Liborio] Univ G DAnnunzio, Dipartimento Sci Biomed, Chieti, Italy. [Seemanova, Eva] Charles Univ Prague, Univ Hosp Prague, Inst Biol & Med Genet, Prague, Czech Republic. [Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Genom Div, Berkeley, CA 94720 USA. [Pennacchio, Len A.] US DOE, Joint Genome Inst, Walnut Creek, CA USA. [Gelb, Bruce D.] Mt Sinai Sch Med, Ctr Mol Cardiol, New York, NY USA. [Gelb, Bruce D.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Gelb, Bruce D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Zenker, Martin] Univ Erlangen Nurnberg, Inst Human Genet, Univ Hosp Erlangen, D-8520 Erlangen, Germany. [Zenker, Martin] Otto Von Guericke Univ, Univ Hosp Magdeburg, Inst Human Genet, Magdeburg, Germany. RP Zenker, M (reprint author), Max Planck Inst Mol Physiol, Dept Biol Struct, Rheinlanddamm 201, D-44139 Dortmund, Germany. EM reza.ahmadian@uni-duesseldorf.de; mtartaglia@iss.it; martin.zenker@med.ovgu.de RI Carta, Claudio/A-7305-2013; Gremer, Lothar/H-9128-2013; Dallapiccola, Bruno/K-8692-2016; OI Gremer, Lothar/0000-0001-7065-5027; Lepri, Francesca Romana/0000-0001-5331-0473; Dallapiccola, Bruno/0000-0002-5031-1013; Silengo, Margherita/0000-0002-6255-1532; Tartaglia, Marco/0000-0001-7736-9672; Stuppia, Liborio/0000-0002-6232-0996 FU European Research Area Network; German Research Foundation (DFG) [AH 92/5-1, KR 3473/1-1, ZE 524/4-1]; German Ministry of Science and Education [01GS08100]; Telethon-Italy [GGP07115]; Associazione Italiana Sindromi di Costello e Cardiofaciocutanea; Collaborazione Italia-USA/malattie rare FX We are grateful to the subjects and their families for participating in this study. We thank A. Diem and B. Quinger (Institute of Human Genetics, Erlangen, Germany), T. Squatriti and S. Venanzi (Istituto Superiore di Sanita, Rome, Italy) and I. Jantke and S. Lorenz (Institut fur Humangenetik, Hamburg, Germany) for skillful technical assistance. The X-ray diffraction datasets were collected at the Swiss Light Source, beamline X10SA, Paul Scherrer Institut, Villigen, Switzerland. This work was supported by grants from the European Research Area Network for research programs on rare diseases (E-Rare) 2009 to M. T., M. Z. and M. R. A. (European Network on Noonan Syndrome and Related Disorders), German Research Foundation (DFG) to M. R. A. (AH 92/5-1) and C. P. K. and M. Z. (KR 3473/1-1 and ZE 524/4-1), Nationales Genomforschungsnetz Plus program of the German Ministry of Science and Education to M. R. A. (BMBF, grant 01GS08100), and Telethon-Italy (GGP07115), 'Associazione Italiana Sindromi di Costello e Cardiofaciocutanea' and 'Collaborazione Italia-USA/malattie rare' to M. T. NR 14 TC 117 Z9 119 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JAN PY 2010 VL 42 IS 1 BP 27 EP 29 DI 10.1038/ng.497 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 536PA UT WOS:000273055100012 PM 19966803 ER PT J AU Hancock, DB Eijgelsheim, M Wilk, JB Gharib, SA Loehr, LR Marciante, KD Franceschini, N van Durme, YMTA Chen, TH Barr, RG Schabath, MB Couper, DJ Brusselle, GG Psaty, BM van Duijn, CM Rotter, JI Uitterlinden, AG Hofman, A Punjabi, NM Rivadeneira, F Morrison, AC Enright, PL North, KE Heckbert, SR Lumley, T Stricker, BHC O'Connor, GT London, SJ AF Hancock, Dana B. Eijgelsheim, Mark Wilk, Jemma B. Gharib, Sina A. Loehr, Laura R. Marciante, Kristin D. Franceschini, Nora van Durme, Yannick M. T. A. Chen, Ting-hsu Barr, R. Graham Schabath, Matthew B. Couper, David J. Brusselle, Guy G. Psaty, Bruce M. van Duijn, Cornelia M. Rotter, Jerome I. Uitterlinden, Andre G. Hofman, Albert Punjabi, Naresh M. Rivadeneira, Fernando Morrison, Alanna C. Enright, Paul L. North, Kari E. Heckbert, Susan R. Lumley, Thomas Stricker, Bruno H. C. O'Connor, George T. London, Stephanie J. TI Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function SO NATURE GENETICS LA English DT Article ID LUNG-FUNCTION DECLINE; SEROTONINERGIC RECEPTORS; GENERAL-POPULATION; REFERENCE VALUES; ADAM33 GENE; FRAMINGHAM; DISEASE; IDENTIFICATION; DESIGN; HEART AB Spirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and its ratio to forced vital capacity (FEV1/FVC), an indicator of airflow obstruction. This meta-analysis included 20,890 participants of European ancestry from four CHARGE Consortium studies: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study and Rotterdam Study. We identified eight loci associated with FEV1/FVC (HHIP, GPR126, ADAM19, AGER-PPT2, FAM13A, PTCH1, PID1 and HTR4) and one locus associated with FEV1 (INTS12-GSTCD-NPNT) at or near genome-wide significance (P < 5 x 10(-8)) in the CHARGE Consortium dataset. Our findings may offer insights into pulmonary function and pathogenesis of chronic lung disease. C1 [Hancock, Dana B.; Loehr, Laura R.; London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Eijgelsheim, Mark; Brusselle, Guy G.; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Rivadeneira, Fernando; Stricker, Bruno H. C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Wilk, Jemma B.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Gharib, Sina A.; Marciante, Kristin D.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Gharib, Sina A.] Univ Washington, Ctr Lung Biol, Seattle, WA 98195 USA. [Loehr, Laura R.; Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Marciante, Kristin D.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [van Durme, Yannick M. T. A.; Brusselle, Guy G.] Univ Ghent, Dept Resp Med, B-9000 Ghent, Belgium. [van Durme, Yannick M. T. A.; Brusselle, Guy G.] Ghent Univ Hosp, B-9000 Ghent, Belgium. [Chen, Ting-hsu; O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Chen, Ting-hsu; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Barr, R. Graham] Columbia Univ, Coll Phys & Surg, Dept Med, Div Gen Med, New York, NY USA. [Barr, R. Graham] Columbia Univ, Coll Phys & Surg, Dept Med, Div Pulm Allergy & Crit Care, New York, NY USA. [Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Schabath, Matthew B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Rivadeneira, Fernando; Stricker, Bruno H. C.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Punjabi, Naresh M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Punjabi, Naresh M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol & Dis Control, Ctr Human Genet, Houston, TX USA. [Enright, Paul L.] Univ Arizona, Coll Publ Hlth, Tucson, AZ USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Stricker, Bruno H. C.] Netherlands Genom Initiat, Rotterdam, Netherlands. [Stricker, Bruno H. C.] Inspectorate Hlth Care, The Hague, Netherlands. [London, Stephanie J.] NIEHS, Lab Resp Biol, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov RI Hancock, Dana/D-8577-2012; Rivadeneira, Fernando/O-5385-2015; Schabath, Matthew/J-3763-2016; OI Rivadeneira, Fernando/0000-0001-9435-9441; Schabath, Matthew/0000-0003-3241-3216; O'Connor, George/0000-0002-6476-3926; Hancock, Dana/0000-0003-2240-3604; London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [ZIA ES043012-11]; Medical Research Council [G0000934]; NCRR NIH HHS [M01 RR000425, M01-RR00425]; NHGRI NIH HHS [U01 HG004402, U01HG004402]; NHLBI NIH HHS [N01 HC-55222, N01 HC015103, N01 HC035129, N01 HC045133, N01 HC095159, N01-HC-25195, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-75150, N01-HC-85079 THROUGH N01-HC-85086, N01HC25195, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC55222, N01HC75150, N01HC85079, N01HC85086, N02-HL-6-4278, R01 HL059367, R01 HL077612, R01 HL086694, R01 HL087641, R01 HL087652, R01HL086694, R01HL087641, R01HL59367, RC1 HL100543, U01 HL080295]; NIDDK NIH HHS [DK063491, P30 DK063491]; NIEHS NIH HHS [Z01 ES043012]; PHS HHS [HHSN268200625226C] NR 76 TC 256 Z9 264 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JAN PY 2010 VL 42 IS 1 BP 45 EP U61 DI 10.1038/ng.500 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 536PA UT WOS:000273055100015 PM 20010835 ER PT J AU Jones, KS Green, PL AF Jones, Kathryn S. Green, Patrick L. TI Cloaked virus slips between cells SO NATURE MEDICINE LA English DT Editorial Material ID T-CELLS; TRANSMISSION; LYMPHOCYTES; RETROVIRUSES AB A common retrovirus encases itself in an extracellular matrix, enabling its transfer between T4 cells. The discovery of this new mode of infectivity has the potential to lead to new ways to combat the virus, human T cell leukemia virus type 1 (HTLV-1), which is associated with cancers and inflammatory disorders (pages 83-89). C1 [Jones, Kathryn S.] NCI, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. [Green, Patrick L.] Ohio State Univ, Ctr Retrovirus Res, Dept Vet Biosci & Mol Virol, Columbus, OH 43210 USA. [Green, Patrick L.] Ohio State Univ, Ctr Retrovirus Res, Dept Immunol, Columbus, OH 43210 USA. [Green, Patrick L.] Ohio State Univ, Ctr Retrovirus Res, Dept Med Genet, Columbus, OH 43210 USA. RP Jones, KS (reprint author), NCI, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. EM joneska@mail.nih.gov FU NCI NIH HHS [R01 CA077556-10, P01 CA100730-10, P01 CA100730, R01 CA077556] NR 12 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2010 VL 16 IS 1 BP 25 EP 27 DI 10.1038/nm0110-25 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 541EA UT WOS:000273395500026 PM 20057417 ER PT J AU Belforte, JE Zsiros, V Sklar, ER Jiang, ZH Yu, G Li, YQ Quinlan, EM Nakazawa, K AF Belforte, Juan E. Zsiros, Veronika Sklar, Elyse R. Jiang, Zhihong Yu, Gu Li, Yuqing Quinlan, Elizabeth M. Nakazawa, Kazu TI Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes SO NATURE NEUROSCIENCE LA English DT Article ID SPATIAL WORKING-MEMORY; PREFRONTAL CORTEX; MICE LACKING; PREPULSE INHIBITION; SYNAPTIC PLASTICITY; BIPOLAR DISORDER; ANIMAL-MODELS; KETAMINE; PSYCHOSIS; PHENCYCLIDINE AB Cortical GABAergic dysfunction may underlie the pathophysiology of psychiatric disorders, including schizophrenia. Here, we characterized a mouse strain in which the essential NR1 subunit of the NMDA receptor (NMDAR) was selectively eliminated in 40-50% of cortical and hippocampal interneurons in early postnatal development. Consistent with the NMDAR hypofunction theory of schizophrenia, distinct schizophrenia-related symptoms emerged after adolescence, including novelty-induced hyperlocomotion, mating and nest-building deficits, as well as anhedonia-like and anxiety-like behaviors. Many of these behaviors were exacerbated by social isolation stress. Social memory, spatial working memory and prepulse inhibition were also impaired. Reduced expression of glutamic acid decarboxylase 67 and parvalbumin was accompanied by disinhibition of cortical excitatory neurons and reduced neuronal synchrony. Postadolescent deletion of NR1 did not result in such abnormalities. These findings suggest that early postnatal inhibition of NMDAR activity in corticolimbic GABAergic interneurons contributes to the pathophysiology of schizophrenia-related disorders. C1 [Belforte, Juan E.; Zsiros, Veronika; Sklar, Elyse R.; Jiang, Zhihong; Nakazawa, Kazu] NIMH, Unit Genet Cognit & Behav, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. [Belforte, Juan E.] NIAAA, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD USA. [Yu, Gu; Quinlan, Elizabeth M.] Univ Maryland, Dept Biol, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. [Li, Yuqing] Univ Alabama, Med Sch Birmingham, Dept Neurol, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL USA. RP Nakazawa, K (reprint author), NIMH, Unit Genet Cognit & Behav, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. EM nakazawk@mail.nih.gov RI Li, Yuqing/G-1596-2011; Nakazawa, Kazutoshi/J-6195-2015 OI Li, Yuqing/0000-0003-1211-5529; Nakazawa, Kazutoshi/0000-0001-5699-9093 FU US National Institute of Mental Health; US National Institute on Alcohol Abuse and Addiction FX We also acknowledge the CURE/Digestive diseases research center at the University of California Los Angeles and the US National Institute of Mental Health Chemical Synthesis and Drug Supply Program for antibodies and risperidone, respectively. This work was supported by the Intramural Research Program of the US National Institute of Mental Health and of the US National Institute on Alcohol Abuse and Addiction. NR 50 TC 361 Z9 366 U1 4 U2 60 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2010 VL 13 IS 1 BP 76 EP U240 DI 10.1038/nn.2447 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 536PM UT WOS:000273056300016 PM 19915563 ER PT J AU Tsujimoto, S Genovesio, A Wise, SP AF Tsujimoto, Satoshi Genovesio, Aldo Wise, Steven P. TI Evaluating self-generated decisions in frontal pole cortex of monkeys SO NATURE NEUROSCIENCE LA English DT Article ID ROSTRAL PREFRONTAL CORTEX; MACAQUE MONKEYS; HUMAN COGNITION; BRAIN-FUNCTION; DEFAULT MODE; AREA-10; TASK; FMRI; REPRESENTATION; HUMANS AB The frontal pole cortex (FPC) expanded markedly during human evolution, but its function remains uncertain in both monkeys and humans. Accordingly, we examined single-cell activity in this area. On every trial, monkeys decided between two response targets on the basis of a 'stay' or 'shift' cue. Feedback followed at a fixed delay. FPC cells did not encode the monkeys' decisions when they were made, but did so later on, as feedback approached. This finding indicates that the FPC is involved in monitoring or evaluating decisions. Using a control task and delayed feedback, we found that decision coding lasted until feedback only when the monkeys combined working memory with sensory cues to 'self-generate' decisions, as opposed to when they simply followed trial-by-trial instructions. A role in monitoring or evaluating self-generated decisions could account for FPC's expansion during human evolution. C1 [Tsujimoto, Satoshi; Genovesio, Aldo; Wise, Steven P.] NIMH, Lab Syst Neurosci, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Tsujimoto, Satoshi] Kobe Univ, Grad Sch Human Dev & Environm, Dev Cognit Neurosci Lab, Nada Ku, Kobe, Hyogo 657, Japan. [Genovesio, Aldo] Univ Roma La Sapienza, Dept Physiol & Pharmacol, Rome, Italy. RP Tsujimoto, S (reprint author), NIMH, Lab Syst Neurosci, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM tsujimoto@ruby.kobe-u.ac.jp RI Tsujimoto, Satoshi/B-8223-2011 FU National Institute of Mental Health [Z01MH-01092]; Ministry of Education, Culture, Sports, Science and Technology, Japan [21119513]; Japan Society for the Promotion of Science FX We thank S. Bunge, G. di Pellegrino, E. Murray, R. Passingham, N. Ramnani and P. Rudebeck for comments on drafts of this manuscript. A. Mitz, J. Fellows and P.-Y. Chen provided technical support. This work was supported by the Division of Intramural Research of the National Institute of Mental Health (Z01MH-01092) and by a Grant-in-Aid for Scientific Research on Innovative Areas (21119513) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. S. T. was supported by a research fellowship from the Japan Society for the Promotion of Science. NR 50 TC 72 Z9 73 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2010 VL 13 IS 1 BP 120 EP U293 DI 10.1038/nn.2453 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 536PM UT WOS:000273056300022 PM 19966838 ER PT J AU Dong, SY Rogan, SC Roth, BL AF Dong, Shuyun Rogan, Sarah C. Roth, Bryan L. TI Directed molecular evolution of DREADDs: a generic approach to creating next-generation RASSLs SO NATURE PROTOCOLS LA English DT Article ID PROTEIN-COUPLED RECEPTORS; EXPRESSION; PATHWAYS; MICE AB G protein-coupled receptors (GPCRs) and their downstream signaling cascades contribute to most physiological processes and a variety of human diseases. Isolating the effects of GPCR activation in an in vivo experimental setting is challenging as exogenous ligands have off-target effects and endogenous ligands constantly modulate the activity of native receptors. Highly specific designer drug-designer receptor complexes are a valuable tool for elucidating the effects of activating particular receptors and signaling pathways within selected cell types in vivo. In this study, we describe a generic protocol for the directed molecular evolution of designer receptors exclusively activated by designer drugs (DREADDs). First, the yeast system is validated with the template receptor. Second, a mutant library is generated by error-prone PCR. Third, the library is screened by drug-dependent yeast growth assays. Mutants exhibiting the desired properties are selected for further rounds of mutagenesis or for characterization in mammalian systems. In total, these steps should take 6-8 weeks of experimentation and should result in the evolution of a receptor to be activated by the chosen ligand. This protocol should help improve the experimental targeting of select cell populations. C1 [Dong, Shuyun; Rogan, Sarah C.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27515 USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Program Neurosci, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Med Chem & Nat Prod, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Carolina Integrated Chem Biol & Drug Discovery Ct, Chapel Hill, NC USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC USA. RP Roth, BL (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27515 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010; OI Dong, Shuyun/0000-0003-2988-6864 FU NARSAD Distinguished Investigator Award; National Institutes of Health; National Institute of General Medical Sciences [GM07040, GM008719]; National Institute of Mental Health [MH087074, MH082441, MH061887] FX We thank Blaine N. Armbruster for his work developing this technique. This study was supported by a NARSAD Distinguished Investigator Award and by the following grants from the National Institutes of Health: GM07040 and GM008719 from the National Institute of General Medical Sciences (S. C. R.); and MH087074 (S. C. R.), MH082441 and MH061887 (B. L. R.) from the National Institute of Mental Health. NR 19 TC 59 Z9 59 U1 3 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2010 VL 5 IS 3 BP 561 EP 573 DI 10.1038/nprot.2009.239 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 564RT UT WOS:000275234900015 PM 20203671 ER PT J AU Arnaoutova, I Kleinman, HK AF Arnaoutova, Irina Kleinman, Hynda K. TI In vitro angiogenesis: endothelial cell tube formation on gelled basement membrane extract SO NATURE PROTOCOLS LA English DT Article ID CAPILLARY-LIKE STRUCTURES; PROGENITOR CELLS; GENE-EXPRESSION; BLOOD-VESSEL; MATRIGEL; DIFFERENTIATION; INVITRO; LINE; IDENTIFICATION; ESTABLISHMENT AB A protocol is presented here for a rapid, quantitative and reliable in vitro angiogenesis assay that can be adapted for high throughput use. Endothelial cells are plated on a gelled basement matrix, their natural substrate, and form capillary-like structures with a lumen. The assay can be used to identify inhibitors or stimulators of angiogenesis, as well as genes and signaling pathways involved in angiogenesis. It has also been used to identify endothelial progenitor cells. This assay involves endothelial cell adhesion, migration, protease activity and tubule formation. This tube formation assay is preferred, as other in vitro assays for angiogenesis, such as cell adhesion, migration and invasion, measure limited steps in the angiogenesis process. The tube formation assay on basement membrane can be completed in a day because transformed endothelial cells form tubes within 3 h, whereas non-transformed endothelial cells form tubes within 6 h. C1 [Arnaoutova, Irina] Trevigen, Gaithersburg, MD USA. [Kleinman, Hynda K.] NIDCR, NIH, Bethesda, MD USA. RP Arnaoutova, I (reprint author), Trevigen, Gaithersburg, MD USA. EM iarnaoutova@trevigen.com; hkleinman@dir.nidcr.nih.gov NR 33 TC 171 Z9 176 U1 8 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2010 VL 5 IS 4 BP 628 EP 635 DI 10.1038/nprot.2010.6 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 577BS UT WOS:000276196500002 PM 20224563 ER PT B AU Stein, DC Patrone, JB Bish, S AF Stein, Daniel C. Patrone, Julia B. Bish, Samuel BE Genco, CA Wetzler, L TI Innate Immune Recognition of Neisseria meningitidis and Neisseria gonorrhoeae SO NEISSERIA: MOLECULAR MECHANISMS OF PATHOGENESIS LA English DT Article; Book Chapter ID OUTER-MEMBRANE-PROTEIN; IMMUNOGLOBULIN A1 PROTEASE; DENDRITIC CELL ACTIVATION; TOLL-LIKE RECEPTORS; FACTOR-KAPPA-B; URETHRAL EPITHELIAL-CELLS; CORTICAL PLAQUE-FORMATION; GENITAL-TRACT INFECTION; HUMAN MUCOSAL SURFACES; CD4(+) T-CELLS AB The existing paradigm in neisserial infections is that these pathogens present a diverse, varying cell surface, and that one of the functions of this variability is that it allows them to avoid the killing actions of the hosts' innate immune system. In this chapter, we will define the important features of the innate immune system as it relates to neisserial disease, review the role of the variable cell surface antigens of N. gonorrhoeae and N. meningitidis in eliciting responses from various host cells, and provide some insights into the molecular basis of disease. We will describe what features are essential on the bacterium for initiating colonization in various anatomical locations and in the different sexes, and review how the host responds to these colonization events (disease vs. asymptomatic colonization). We will also review the molecular mechanisms by which cells of the innate immune system become activated, and how different activation mechanisms can lead to different disease outcomes. C1 [Stein, Daniel C.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Patrone, Julia B.] Johns Hopkins Univ, Appl Phys Lab, Milton S Eisenhower Res Ctr, Laurel, MD USA. [Bish, Samuel] NCI, NIH, Technol Transfer Ctr, Rockville, MD USA. RP Stein, DC (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. EM dcstein@umd.edu; julia.patrone@jhuapl.edu; bishse@mail.nih.gov NR 237 TC 2 Z9 2 U1 2 U2 5 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-51-6 PY 2010 BP 95 EP 122 PG 28 WC Biotechnology & Applied Microbiology; Public, Environmental & Occupational Health SC Biotechnology & Applied Microbiology; Public, Environmental & Occupational Health GA BMU20 UT WOS:000273572000007 ER PT B AU Ma, DQ Jones, D AF Ma, Deqin Jones, Dan BE Jones, D TI Post-transplant Immune Function and the Development of Lymphoma SO NEOPLASTIC HEMATOPATHOLOGY: EXPERIMENTAL AND CLINICAL APPROACHES SE Contemporary Hematology LA English DT Article; Book Chapter DE Post-transplant lymphoproliferative disorders; Lymphoma, Epstein-Barr virus (EBV); Epstein-Barr virus, quantitative PCR; Cytomegalovirus; Hepatosplenic T-cell lymphoma, post-transplant; Diffuse large B-cell lymphoma, post-transplant; Donor lymphocyte infusion; Post-transplant, treatment for lymphoma ID EPSTEIN-BARR-VIRUS; STEM-CELL TRANSPLANTATION; CYTOTOXIC T-CELLS; LYMPHOPROLIFERATIVE DISORDERS; ORGAN-TRANSPLANTATION; MALIGNANCIES; CATEGORIES; RECIPIENTS; DISEASE AB Both hematopoietic stem cell transplantation and solid organ transplantation are associated with short-term and long-term immune deficits that result in an increased risk of disseminated infection and malignancy. Here, we discuss these risk factors and the time-course for the development of post-transplant lymphoproliferative disorders in each transplant type. C1 [Ma, Deqin] NIH, Dept Anat Pathol, Bethesda, MD 20892 USA. [Jones, Dan] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. RP Ma, DQ (reprint author), NIH, Dept Anat Pathol, Bldg 10, Bethesda, MD 20892 USA. EM dajones@mdanderson.org; dajones@mdanderson.org NR 24 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 978-1-60761-383-1 J9 CONTEMP HEMATOL PY 2010 BP 521 EP 527 DI 10.1007/978-1-60761-384-8_30 D2 10.1007/978-1-60761-384-8 PG 7 WC Hematology SC Hematology GA BNI24 UT WOS:000274630100030 ER PT J AU Minev, E Unruh, M Shlipak, MG Simsonick, E Yaffe, K Leak, TS Newman, AB Fried, LF AF Minev, Evgueni Unruh, Mark Shlipak, Michael G. Simsonick, Eleanor Yaffe, Kristine Leak, Tennille S. Newman, Anne B. Fried, Linda F. CA Hlth ABC Study TI Association of Cystatin C and Depression in Healthy Elders: The Health, Aging and Body Composition Study SO NEPHRON CLINICAL PRACTICE LA English DT Article DE Depression, elderly; Cystatin C; Chronic kidney disease ID CHRONIC KIDNEY-DISEASE; RENAL-TRANSPLANTATION; HEMODIALYSIS-PATIENTS; PREVALENCE; DIAGNOSIS; OUTCOMES; DEATH AB Background/Aims: Depression is highly prevalent in individuals with advanced kidney disease, but is less well studied in individuals with milder disease. We evaluated the association between kidney function and depression in the Health, Aging and Body Composition (Health ABC) study. Methods: The study enrolled 3,075 community-dwelling black and white adults aged 70-79 years. Kidney function was measured by cystatin C and estimated glomerular filtration rate (eGFR). The main outcome was incident treated depression. Results: 52% of participants had low (<= 1.0), 33% intermediate (> 1-1.25) and 15% high cystatin C (> 1.25). Kidney function and depression were not associated at baseline. Of 2,731 nondepressed participants at baseline, 95 developed incident depression during follow-up. In unadjusted Cox proportional hazard models, hazard ratios (HR) for incident depression were 1.89 (95% confidence interval (CI) 1.21-2.97) for the intermediate and 2.17 (CI 1.24-3.79) for the high cystatin C group. Intermediate (HR = 1.84) and high (HR = 2.1) serum cystatin C remained associated with incident depression in adjusted models. Chronic kidney disease, defined by an eGFR < 60 ml/min/1.73 m(2), was not associated with depression. Conclusion: Participants with higher cystatin C had an increased likelihood of developing treated depression. Future studies should target this high-risk group. Copyright (C) 2010 S. Karger AG, Basel C1 [Minev, Evgueni; Unruh, Mark; Fried, Linda F.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15216 USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15216 USA. [Leak, Tennille S.; Newman, Anne B.; Fried, Linda F.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15216 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Gen Internal Med Sect, Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Simsonick, Eleanor] NIA, NIH, Baltimore, MD 21224 USA. RP Minev, E (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, 3550 Terrace St, Pittsburgh, PA 15216 USA. EM evgueni.minev@gmail.com RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [P30 AG024827] NR 21 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2110 J9 NEPHRON CLIN PRACT JI Nephron. Clin. Pract. PY 2010 VL 116 IS 3 BP C241 EP C246 DI 10.1159/000317205 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 621OI UT WOS:000279588200015 PM 20606485 ER PT J AU Xu, QH Hendry, BM Maden, M Lu, HY Wong, YF Rankin, AC Noor, M Kopp, JB AF Xu, Qihe Hendry, Bruce M. Maden, Malcolm Lu, Huiyan Wong, Yuen Fei Rankin, Alexandra C. Noor, Mazhar Kopp, Jeffrey B. TI Kidneys of Alb/TGF-beta(1) Transgenic Mice Are Deficient in Retinoic Acid and Exogenous Retinoic Acid Shows Dose-Dependent Toxicity SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE All-trans retinoic acid; Transforming growth factor-beta(1); Connective tissue growth factor; Retinal dehydrogenase 2; Fibrosis ID LUNG EPITHELIAL-CELLS; RAT-LIVER FIBROSIS; GROWTH-FACTOR; TGF-BETA; COLLAGEN-SYNTHESIS; HUMAN SKIN; ANGIOTENSIN-II; RECEPTORS; PROTEINS; DISEASE AB Background: Alb/TGF-beta(1) transgenic mice overexpress active transforming growth factor-beta(1) (TGF-beta(1)) in the liver, leading to increased circulating levels of the cytokine and progressive renal fibrosis. This study was designed to explore if exogenous all-trans retinoic acid (tRA) prevents renal fibrosis in this animal model. Methods: The retinoid profile in kidney and liver of wild-type and Alb/TGF-beta(1) transgenic mice was examined by high-performance liquid chromatography and slow-release pellets containing different amounts of tRA were implanted subcutaneously to treat the Alb/TGF-beta(1) transgenic mice, starting at 1 week of age; mice were sacrificed 2 weeks later. Results: Kidneys of 3-week-old wild-type mice had abundant tRA, which was completely absent in kidneys of the transgenic mice. Low doses of tRA (6-10.7 mg/kg/day) failed to affect renal fibrosis although it tended to suppress the mRNA expression of some molecular markers of fibrosis and retinal dehydrogenase 2 (RALDH2), a gene encoding a key tRA-synthesising enzyme. These tendencies disappeared, mortality tended to increase and RALDH2 and connective tissue growth factor (CTGF) mRNAs significantly increased in the medium-dose group (12.7-18.8 mg/kg/day). High doses (20.1-27.4 mg/kg/day) showed even higher toxicity with increased renal fibrosis and significant mortality. Conclusions: Alb/TGF-beta(1) transgenic mice are characterised by depletion of endogenous renal tRA. Exogenous tRA dose-dependently increases mortality and kidney fibrosis, which is associated with dose-dependent regulation of renal RALDH2 and CTGF mRNA expression. Copyright (C) 2010 S. Karger AG, Basel C1 [Xu, Qihe] Kings Coll London, Dept Renal Med, Rayne Inst, London SE5 9NU, England. [Hendry, Bruce M.] Univ Florida, Dept Zool, Gainesville, FL 32611 USA. [Lu, Huiyan; Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Xu, QH (reprint author), Kings Coll London, Dept Renal Med, Rayne Inst, 123 Coldharbour Lane, London SE5 9NU, England. EM qihe.xu@kcl.ac.uk FU Kidney Research UK; British Heart Foundation; Royal Free Peter Samuel Fund; UCL Bogue Fellowship Fund; UCL VIP; Intramural Research Program of the NIDDK, NIH FX This work is supported by Kidney Research UK, British Heart Foundation, Royal Free Peter Samuel Fund, UCL Bogue Fellowship Fund and a UCL VIP award to Q. X. and an Intramural Research Program of the NIDDK, NIH awarded to J. B. K. We are grateful to Dr. Duolao Wang ( London School of Hygiene & Tropical Medicine, London, UK) for critically reviewing the statistical methodology in the manuscript. NR 29 TC 4 Z9 4 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PY 2010 VL 114 IS 4 BP E127 EP E132 DI 10.1159/000276587 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 584SP UT WOS:000276773400001 PM 20110732 ER PT J AU Stranahan, AM Mattson, MP AF Stranahan, Alexis M. Mattson, Mark P. TI Selective Vulnerability of Neurons in Layer II of the Entorhinal Cortex during Aging and Alzheimer's Disease SO NEURAL PLASTICITY LA English DT Review ID CIRCUIT-SPECIFIC ALTERATIONS; SPATIAL-LEARNING IMPAIRMENT; SYNAPTIC PLASTICITY; GENE-EXPRESSION; ELECTROPHYSIOLOGICAL PROPERTIES; MORPHOLOGICAL-CHARACTERISTICS; PARAHIPPOCAMPAL REGION; AMYLOID DEPOSITION; HIPPOCAMPAL REGION; PRINCIPAL NEURONS AB All neurons are not created equal. Certain cell populations in specific brain regions are more susceptible to age-related changes that initiate regional and system-level dysfunction. In this respect, neurons in layer II of the entorhinal cortex are selectively vulnerable in aging and Alzheimer's disease (AD). This paper will cover several hypotheses that attempt to account for age-related alterations among this cell population. We consider whether specific developmental, anatomical, or biochemical features of neurons in layer II of the entorhinal cortex contribute to their particular sensitivity to aging and AD. The entorhinal cortex is a functionally heterogeneous environment, and we will also review data suggesting that, within the entorhinal cortex, there is subregional specificity for molecular alterations that may initiate cognitive decline. Taken together, the existing data point to a regional cascade in which entorhinal cortical alterations directly contribute to downstream changes in its primary afferent region, the hippocampus. C1 [Stranahan, Alexis M.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA. [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Stranahan, AM (reprint author), Johns Hopkins Univ, Dept Psychol & Brain Sci, Ames Hall,3400 N Charles St, Baltimore, MD 21218 USA. EM alexis.stranahan@jhu.edu RI Mattson, Mark/F-6038-2012 FU Ford Foundation; NIH NRSA [F32 AG034818-01]; National Institute on Aging through the National Institutes of Health FX A. M. Stranahan is supported by the Ford Foundation and by an NIH NRSA postdoctoral fellowship (F32 AG034818-01). M. P. Mattson is supported by the Intramural Program of the National Institute on Aging through the National Institutes of Health. NR 65 TC 45 Z9 46 U1 0 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0792-8483 J9 NEURAL PLAST JI Neural. Plast. PY 2010 AR 108190 DI 10.1155/2010/108190 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 707BW UT WOS:000286262500001 ER PT J AU Rajaraman, P Hutchinson, A Wichner, S Black, PM Fine, HA Loeffler, JS Selker, RG Shapiro, WR Rothman, N Linet, MS Inskip, PD AF Rajaraman, Preetha Hutchinson, Amy Wichner, Sara Black, Peter M. Fine, Howard A. Loeffler, Jay S. Selker, Robert G. Shapiro, William R. Rothman, Nathaniel Linet, Martha S. Inskip, Peter D. TI DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma SO NEURO-ONCOLOGY LA English DT Article DE acoustic neuroma; brain; case-control; DNA repair; glioma; meningioma; neoplasm; polymorphism; tumor ID BREAST-CANCER RISK; BRAIN-TUMORS; COMPREHENSIVE ANALYSIS; VARIANTS; XRCC1; ERCC1 AB Although the etiology of primary brain tumors is largely unknown, prior studies suggest that DNA repair polymorphisms may influence risk of glioma. Altered DNA repair is also likely to affect the risk of meningioma and acoustic neuroma, but these tumors have not been well studied. We estimated the risk of glioma (n = 362), meningioma (n = 134), and acoustic neuroma (n = 69) in non-Hispanic whites with respect to 36 single nucleotide polymorphisms from 26 genes involved in DNA repair in a hospital-based, case-control study conducted by the National Cancer Institute. We observed significantly increased risk of meningioma with the T variant of GLTSCR1 rs1035938 (OR(CT/TT) = 3.5; 95% confidence interval: 1.8-6.9; P(trend) .0006), which persisted after controlling for multiple comparisons (P = .019). Significantly increased meningioma risk was also observed for the minor allele variants of ERCC4 rs1800067 (P(trend) .01); MUTYH rs3219466 (P(trend) .02), and PCNA rs25406 (P(trend) .03). The NBN rs1805794 minor allele variant was associated with decreased meningioma risk (P(trend) .006). Risk of acoustic neuroma was increased for the ERCC2 rs1799793 (P(trend) .03) and ERCC5 rs17655 (P(trend) .05) variants and decreased for the PARP1 rs1136410 (P(trend) .03). Decreased glioma risk was observed with the XRCC1 rs1799782 variant (P(trend) .04). Our results suggest that common DNA repair variants may affect the risk of adult brain tumors, especially meningioma. C1 [Rajaraman, Preetha; Wichner, Sara; Rothman, Nathaniel; Linet, Martha S.; Inskip, Peter D.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Hutchinson, Amy] NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, Adv Technol Program,SAIC Frederick Inc, Frederick, MD 21701 USA. [Black, Peter M.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Selker, Robert G.] Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. [Shapiro, William R.] St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. RP Rajaraman, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Room 7085, Bethesda, MD 20892 USA. EM rajarama@mail.nih.gov FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services; National Cancer Institute, National Institutes of Health [N01-CO-12400] FX This research was supported by intramural funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. NR 25 TC 85 Z9 88 U1 1 U2 8 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2010 VL 12 IS 1 BP 37 EP 48 DI 10.1093/neuonc/nop012 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 546BE UT WOS:000273781300007 PM 20150366 ER PT J AU Asthagiri, AR Mehta, GU Zach, L Li, XB Butman, JA Camphausen, KA Lonser, RR AF Asthagiri, Ashok R. Mehta, Gautam U. Zach, Leor Li, Xiaobai Butman, John A. Camphausen, Kevin A. Lonser, Russell R. TI Prospective evaluation of radiosurgery for hemangioblastomas in von Hippel-Lindau disease SO NEURO-ONCOLOGY LA English DT Article DE central nervous system hemangioblastoma; radiosurgery; treatment; von Hippel-Lindau disease ID GAMMA-KNIFE RADIOSURGERY; CENTRAL-NERVOUS-SYSTEM; SURGICAL-MANAGEMENT; STEREOTACTIC RADIOSURGERY; INTRACRANIAL HEMANGIOBLASTOMAS; NATURAL-HISTORY; BRAIN; SURGERY AB To determine the effectiveness of stereotactic radiosurgery (SRS) treatment to central nervous system (CNS) hemangioblastomas in von Hippel-Lindau disease (VHL), we analyzed long-term results in VHL patients treated with SRS. Patients were enrolled in a prospective VHL natural history study, undergoing SRS treatment of CNS hemangioblastomas. Treatment regimens, serial clinical evaluations, and longitudinal imaging data were analyzed. Twenty VHL patients (10 males and 10 females) underwent SRS treatment of 44 CNS hemangioblastomas (39 cerebellar and 5 brainstem). Mean (+/- SD) age at treatment was 37.5 +/- 12.0 years (range: 13-67). Mean follow-up was 8.5 +/- 3.2 years (range: 3.0-17.6 years). All patients were alive at last follow-up. Mean treated tumor volume was 0.5 +/- 0.7 cm(3) (range: 0.01-3.6 cm(3)). Mean prescription dose was 18.9 Gy (range: 12-24 Gy) at the tumor margin. Local control rate at 2, 5, 10, and 15 years after SRS treatment was 91%, 83%, 61%, and 51%, respectively. Univariate analysis did not identify variables associated (P > .05) with worse tumor control at last follow-up. Thirty-three percent of SRS-treated small (<1.0cm diameter), asymptomatic tumors progressed over a long-term follow-up. There were no long-term adverse radiation effects. Although SRS treatment of hemangioblastomas in VHL has a low risk for adverse radiation effects, it is associated with diminishing control over a long-term follow-up. These results indicate that SRS should not be used to prophylactically treat asymptomatic tumors and should be reserved for the treatment of tumors that are not surgically resectable. C1 [Asthagiri, Ashok R.; Mehta, Gautam U.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Zach, Leor; Camphausen, Kevin A.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Li, Xiaobai] Natl Inst Neurol Disorders & Stroke, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Asthagiri, AR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM asthagiria@ninds.nih.gov RI Butman, John/A-2694-2008; Butman, John/J-2780-2013; OI Butman, John/0000-0002-1547-9195; Mehta, Gautam/0000-0002-8009-6430 FU National Institute of Neurologic Disorders and Stroke at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurologic Disorders and Stroke at the National Institutes of Health. NR 31 TC 34 Z9 35 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2010 VL 12 IS 1 BP 80 EP 86 DI 10.1093/neuonc/nop018 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 546BE UT WOS:000273781300011 PM 20150370 ER PT J AU Raizer, JJ Abrey, LE Lassman, AB Chang, SM Lamborn, KR Kuhn, JG Yung, WKA Gilbert, MR Aldape, KD Wen, PY Fine, HA Mehta, M DeAngelis, LM Lieberman, F Cloughesy, TF Robins, HI Dancey, J Prados, MD AF Raizer, Jeffrey J. Abrey, Lauren E. Lassman, Andrew B. Chang, Susan M. Lamborn, Kathleen R. Kuhn, John G. Yung, W. K. Alfred Gilbert, Mark R. Aldape, Kenneth D. Wen, Patrick Y. Fine, Howard A. Mehta, Minesh DeAngelis, Lisa M. Lieberman, Frank Cloughesy, Timothy F. Robins, H. Ian Dancey, Janet Prados, Michael D. CA N Amer Brain Tumor Consortium TI A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas SO NEURO-ONCOLOGY LA English DT Article DE erlotinib; glioblastoma; glioma; meningioma; pharmacokinetics ID CONFERS ENHANCED TUMORIGENICITY; TYROSINE-KINASE INHIBITOR; GROWTH-FACTOR RECEPTORS; BRAIN-TUMOR CONSORTIUM; PHARMACOKINETICS; TEMOZOLOMIDE; COMMON; CELLS AB The objective of this phase I study was to determine the maximal tolerated dose (MTD) of erlotinib in patients with re current malignant gliomas (MGs) or recurrent meningiomas on enzyme-inducing antiepileptic drugs (EIAEDs). Dose escalation was by a standard 3 x 3 design. The initial starting dose of erlotinib was 150 mg daily. If no dose-limiting toxicity (DLT) was observed, then dose escalation occurs as follows: 200 mg/day, 275 mg/day, and then increased in 125 mg increments until the MTD was reached. The MTD was defined as the dose where <= 1 of 6 patients experienced a DLT and the dose above had 2 or more DLTs. The MTD was 650 mg/day; the observed DLTs were grade 3 rash in 2 patients at 775 mg/day. Pharmacokinetic analysis showed a significant influence of EIAEDs on the metabolism of erlotinib when compared with our phase 11 data published separately. Primary toxicities were rash and diarrhea. The MTD of erlotinib in patients receiving EIAEDs is substantially higher than the standard dose of 150 mg. This has important implications for further development of this drug in the treatment of MG as well as the optimal management of patients with other malignancies such as NSCLC who are on enzyme-inducing drugs. C1 [Raizer, Jeffrey J.] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Abrey, Lauren E.; Lassman, Andrew B.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chang, Susan M.; Lamborn, Kathleen R.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Yung, W. K. Alfred; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Mehta, Minesh; Robins, H. Ian] Univ Wisconsin Hosp, Madison, WI USA. [Lieberman, Frank] Univ Pittsburgh, Med Ctr Canc Pavil, Div Neurooncol, Pittsburgh, PA USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Neurooncol Program, Los Angeles, CA 90095 USA. [Dancey, Janet] Ontario Inst Canc Res, Toronto, ON, Canada. RP Raizer, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol, 710 N Lake Shore Dr,Abbott Hall 1123, Chicago, IL 60611 USA. EM jraizer@nmff.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NABTC [CA62399, CA62422]; GCRC [M01-RR00079, CA62426, CA62412, CA16672, U01CA62407-08, U01CA6242108, M01 RR03186, U01CA62405, M01-RR00056, U01 CA62399, M01-RR0865]; [5-U01CA62399-09] FX Grant Support: 5-U01CA62399-09 (J.J.R., L.E.A., A.B.L., and L.M.D.); NABTC # CA62399 and Member # CA62422, GCRC Grant # M01-RR00079 (S.M.C., K.R.L., and M.D.P.); CA62426 (J.G.K.); CA62412, GCRC Grant # CA16672 (W.K.A.Y. and M.R.G.); U01CA62407-08 (P.Y.W.), U01CA6242108, GCRC Grant # M01 RR03186 (M.M. and H.I.R.); U01CA62405, GCRC Grant # M01-RR00056 (F.L.); U01 CA62399, GCRC Grant # M01-RR0865 (T.F.C.). NR 16 TC 23 Z9 26 U1 0 U2 5 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2010 VL 12 IS 1 BP 87 EP 94 DI 10.1093/neuonc/nop017 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 546BE UT WOS:000273781300012 PM 20150371 ER PT J AU Raizer, JJ Abrey, LE Lassman, AB Chang, SM Lamborn, KR Kuhn, JG Yung, WKA Gilbert, MR Aldape, KA Wen, PY Fine, HA Mehta, M DeAngelis, LM Lieberman, F Cloughesy, TF Robins, HI Dancey, J Prados, MD AF Raizer, Jeffrey J. Abrey, Lauren E. Lassman, Andrew B. Chang, Susan M. Lamborn, Kathleen R. Kuhn, John G. Yung, W. K. Alfred Gilbert, Mark R. Aldape, Kenneth A. Wen, Patrick Y. Fine, Howard A. Mehta, Minesh DeAngelis, Lisa M. Lieberman, Frank Cloughesy, Timothy F. Robins, H. Ian Dancey, Janet Prados, Michael D. CA N Amer Brain Tumor Consortium TI A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy SO NEURO-ONCOLOGY LA English DT Article DE erlotinib; glioblastoma; glioma; meningioma; pharmacokinetics ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; CONFERS ENHANCED TUMORIGENICITY; RADIATION-THERAPY; KINASE INHIBITORS; PROTEIN-KINASE; I/II TRIAL; GEFITINIB; TEMOZOLOMIDE; BRAIN AB Patients with (a) recurrent malignant glioma (MG): glioblastoma (GBM) or recurrent anaplastic glioma (AG), and (b) nonprogressive (NP) GBM following radiation therapy (RT) were eligible. Primary objective for recurrent MG was progression-free survival at 6 months (PFS-6) and overall survival at 12 months for NP GBM post-RT. Secondary objectives for recurrent MGs were response, survival, assessment of toxicity, and pharmacokinetics (PKs). Treatment with enzyme-inducing antiepileptic drugs was not allowed. Patients received 150 mg/day erlotinib. Patients requiring surgery were treated 7 days prior to tumor removal for PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) and intracellular signaling pathways. Ninety-six patients were evaluable (53 recurrent MG and 43 NP GBM); 5 patients were not evaluable for response. PFS-6 in recurrent GBM was 3% with a median PFS of 2 months; PFS-6 in recurrent AG was 27% with a median PFS of 2 months. Twelve-month survival was 57% in NP GBMs post-RT. Primary toxicity was dermatologic. The tissue-to-plasma ratio normalized to nanograms per gram dry weight for erlotinib and OSI-420 ranged from 25% to 44% and 30% to 59%, respectively, for pretreated surgical patients. No effect on EGFR or intratumoral signaling was seen. Patients with NP GBM post-RT who developed rash in cycle 1 had improved survival (P < .001.). Single-agent activity of erlotinib is minimal for recurrent MGs and marginally beneficial following RT for NP GBM patients. Development of rash in cycle 1 correlates with survival in patients with NP GBM after RT. C1 [Raizer, Jeffrey J.] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Abrey, Lauren E.; Lassman, Andrew B.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chang, Susan M.; Lamborn, Kathleen R.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Yung, W. K. Alfred; Gilbert, Mark R.; Aldape, Kenneth A.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Mehta, Minesh; Robins, H. Ian] Univ Wisconsin Hosp, Madison, WI USA. [Lieberman, Frank] Univ Pittsburgh, Med Ctr Canc Pavil, Div Neurooncol, Pittsburgh, PA USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Neurooncol Program, Los Angeles, CA 90095 USA. [Dancey, Janet] Ontario Inst Canc Res, Toronto, ON, Canada. RP Raizer, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol, 710 N Lake Shore Dr,Abbott Hall 1123, Chicago, IL 60611 USA. EM jraizer@nmff.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NABTC [CA62399, CA62422]; GCRC [M01-RR00079, CA62426, CA62412,, CA16672, U01CA62407-08, U01CA62421-08, M01 RR03186, U01CA62405, M01-RR00056, U01CA62399, M01-RR0865]; [5-U01CA62399-09] FX Grant Support: 5-U01CA62399-09 (J.J.R., L.E.A., A.B.L., and L.M.D.); NABTC # CA62399 and Member # CA62422, GCRC Grant # M01-RR00079 (S.M.C., K.R.L., and M.D.P.); CA62426 (J.G.K.); CA62412, GCRC Grant # CA16672 (W.K.A.Y. and M.R.G.); U01CA62407-08 (P.Y.W.); U01CA62421-08, GCRC Grant # M01 RR03186 (M.M. and H.I.R.); U01CA62405, GCRC Grant # M01-RR00056 (F.L.); U01CA62399, GCRC Grant # M01-RR0865 (T.F.C.). NR 43 TC 119 Z9 123 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2010 VL 12 IS 1 BP 95 EP 103 DI 10.1093/neuonc/nop015 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 546BE UT WOS:000273781300013 PM 20150372 ER PT J AU Momeni, P DeTucci, K Straub, RE Weinberger, DR Davies, P Grafman, J Hardy, J Huey, ED AF Momeni, Parastoo DeTucci, Karen Straub, Richard E. Weinberger, Daniel R. Davies, Peter Grafman, Jordan Hardy, John Huey, Edward D. TI Progranulin (GRN) in two siblings of a Latino family and in other patients with Schizophrenia SO NEUROCASE LA English DT Article DE Frontotemporal dementia; Schizophrenia; Genetics; Progranulin; Psychiatric disorders ID FRONTOTEMPORAL DEMENTIA; MUTATIONS; VARIABILITY; PHENOTYPE; SERIES; TAU AB Schizophrenia has been linked to a region on chromosome 17q21 in Latino populations (Escamilla et al., 2009). Mutations of a gene at this location (GRN) are associated with frontotemporal dementia. A recent study demonstrated that patients with frontotemporal dementia who presented with symptoms of schizophrenia show neuropathological findings consistent with GRN mutations, but were not tested for GRN mutations (Velakoulis, Walterfang, Mocellin, Pantelis, McLean, 2009). The current study describes a Latino family in which two siblings have schizophrenia and one has frontotemporal dementia. We sequenced GRN in one of the siblings with frontotemporal dementia and one of the siblings with schizophrenia. The siblings both have a loss-of-function GRN mutation. This finding, in conjunction with other studies (Escamilla et al., 2009; Velakoulis et al., 2009), suggests that there may be an association between schizophrenia, frontotemporal dementia, and GRN mutations in Latino populations that should be investigated further. C1 [Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Dept Pharmacol & Neurosci, Lubbock, TX 79430 USA. [Hardy, John] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [DeTucci, Karen; Grafman, Jordan; Huey, Edward D.] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA. [Straub, Richard E.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Davies, Peter; Huey, Edward D.] N Shore Long Isl Jewish Healthcare Syst, Litwin Zucker Ctr Res Alzheimers Dis & Memory Dis, Manhasset, NY USA. [Davies, Peter] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. [Hardy, John] UCL, Dept Mol Neurosci, London, England. [Hardy, John] UCL, Reta Lila Weston Inst Neurol Studies, Inst Neurol, London, England. RP Momeni, P (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Dept Pharmacol & Neurosci, Lubbock, TX 79430 USA. EM parastoo.momeni@ttuhsc.edu RI Hardy, John/C-2451-2009; OI Grafman, Jordan H./0000-0001-8645-4457 FU National Institutes of Health/The National Institute of Neurological Disorders and Stroke/The National Institute on Aging/The National Institute of Mental Health, NINDS [1K99NS060766-01]; Litwin-Zucker Center for Research on Alzheimer's Disease and Memory Disorders FX This study was supported by the intramural programs of The National Institutes of Health/The National Institute of Neurological Disorders and Stroke/The National Institute on Aging/The National Institute of Mental Health, NINDS grant 1K99NS060766-01 (EDH), and the Litwin-Zucker Center for Research on Alzheimer's Disease and Memory Disorders (EDH). We thank Pablo V. Gejman for providing us with DNA samples from schizophrenia patients, Eric Wassermann for neurological examinations, the NINDS Clinical Center nurses for patient care, the assistance of the community physicians involved in the care of the patients, and all of the subjects for their generous participation. NR 16 TC 20 Z9 20 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PY 2010 VL 16 IS 3 BP 273 EP 279 AR PII 918660291 DI 10.1080/13554790903456209 PG 7 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 602FQ UT WOS:000278124300007 PM 20087814 ER PT J AU Burdick, A Foote, KD Goodman, W Ward, HE Ricciuti, N Murphy, T Haq, I Okun, MS AF Burdick, Adam Foote, Kelly D. Goodman, Wayne Ward, Herbert E. Ricciuti, Nicola Murphy, Tanya Haq, Ihtsham Okun, Michael S. TI Lack of benefit of accumbens/capsular deep brain stimulation in a patient with both tics and obsessive-compulsive disorder SO NEUROCASE LA English DT Article DE Tourette's syndrome; Deep brain stimulation; Nucleus accumbens; Anterior limb of internal capsule ID TOURETTE-SYNDROME; LIMBIC LEUKOTOMY; HABIT REVERSAL; THALAMUS; SURGERY; TRIAL; SCALE AB Lay summary: This case report illustrates lack of clinical efficacy of deep brain stimulation (DBS) for control of tics in a case of mild Tourette syndrome (TS) with severe comorbid obsessive-compulsive disorder (OCD). The brain target for stimulation was the anterior limb internal capsule (ALIC). Objective: To investigate the effect of anterior limb of internal capsule/nucleus accumbens (ALIC-NA) DBS on mild motor and vocal tics in a Tourette syndrome (TS) patient with severe OCD. Background: The optimum target to address symptoms of TS with DBS remains unknown. Earlier lesional therapy utilized thalamic targets and also the ALIC for select cases which had been diagnosed with other psychiatric disorders. Evidence regarding the efficacy of DBS for the symptoms of TS may aid in better defining a brain target's suitability for use. We report efficacy data on ALIC-NA DBS in a patient with severe OCD and mild TS. Methods: A 33-year-old man underwent bilateral ALIC-NA DBS. One month following implantation, a post-operative CT scan was obtained to verify lead locations. Yale Global Tic Severity Scales (YGTSS) and modified Rush Videotape Rating scales (MRVRS) were obtained throughout the first 6 months, as well as careful clinical examinations by a specialized neurology and psychiatry team. The patient has been followed for 30 months. Results: YGTSS scores worsened by 17% during the first 6 months. MRVRS scores also worsened over 30 total months of follow-up. There was a lack of clinically significant tic reduction although subjectively the patient felt tics improved mildly. Conclusion: DBS in the ALIC-NA failed to effectively address mild vocal and motor tics in a patient with TS and severe comorbid OCD. C1 [Burdick, Adam; Foote, Kelly D.; Okun, Michael S.] Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. [Goodman, Wayne] NIMH, Bethesda, MD 20892 USA. [Ward, Herbert E.; Ricciuti, Nicola] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. [Murphy, Tanya] Univ S Florida, Dept Psychiat & Behav Med, Tampa, FL USA. [Haq, Ihtsham] Wake Forest Univ, Dept Neurol, Winston Salem, NC 27109 USA. [Okun, Michael S.] Univ Florida, Dept Neurol, Gainesville, FL USA. RP Okun, MS (reprint author), Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA. EM okun@neurology.ufl.edu OI Okun, Michael/0000-0002-6247-9358 FU NIH/NIMH; Eric and Jennifer Scott Fund; NIH [R21 MH064161]; University of Florida Foundation FX NIH/NIMH, Eric and Jennifer Scott Fund. This study was supported partially by a grant from the NIH (R21 MH064161; PI Goodman), and also through the University of Florida Foundation. NR 32 TC 36 Z9 38 U1 2 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1355-4794 J9 NEUROCASE JI Neurocase PY 2010 VL 16 IS 4 BP 321 EP 330 AR PII 919429312 DI 10.1080/13554790903560422 PG 10 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 626JZ UT WOS:000279963600007 PM 20178034 ER PT J AU Zhang, M Hu, HL Zhang, XL Lu, WN Lim, J Eysteinsson, T Jacobson, KA Laties, AM Mitchell, CH AF Zhang, Mei Hu, Huiling Zhang, Xiulan Lu, Wennan Lim, Jason Eysteinsson, Thor Jacobson, Kenneth A. Laties, Alan M. Mitchell, Claire H. TI The A(3) adenosine receptor attenuates the calcium rise triggered by NMDA receptors in retinal ganglion cells SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE A(3) adenosine receptor; NMDA receptor; Glutamate; ATP; Purinergic signaling; Neuroprotection; Excitotoxicity; Retinal ganglion cells ID GLUCOSE DEPRIVATION EPISODES; ISCHEMIC BRAIN-INJURY; HAMSTER OVARY CELLS; SYNAPTIC-TRANSMISSION; NEURONS; ACTIVATION; A(1); ANTAGONISTS; CHANNELS; AGONIST AB The A(3) adenosine receptor is emerging as an important regulator of neuronal signaling, and in some situations receptor stimulation can limit excitability. As the NMDA receptor frequently contributes to neuronal excitability, this study examined whether A(3) receptor activation Could alter the calcium rise accompanying NMDA receptor stimulation. Calcium levels were determined from fura-2 imaging of isolated rat retinal ganglion cells as these neurons possess both receptor types. Brief application of glutamate or NMDA led to repeatable and reversible elevations of intracellular calcium. The A(3) agonist Cl-IB-MECA reduced the response to both glutamate and NMDA. While adenosine mimicked the effect of Cl-IB-MECA, the A(3) receptor antagonist MRS 1191 impeded the block by adenosine, implicating a role for the A(3) receptor in response to the natural agonist. The A, receptor antagonist DPCPX provided additional inhibition, implying a contribution from both A, and A(3) adenosine receptors. The novel A3 agonist MRS 3558 (1'S,2'R,3'S,4'R,5'S)-4-(2-chloro-6-(3-chlorobenzylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methyl-bicyclo [3.1.0] hexane-1-carboxamide and mixed A(1)/A(3) agonist MRS 3630 (1'S,2'R,3'S,4'R,5'S)-4-(2-chloro-6-(cyclopentylamino)-9H-purin-9-yl)-2,3-dihydroxy-N-methylbicyclo [3.1.0] hexane-1-carboxamide also inhibited the Calcium rise induced by NMDA. Low levels of MRS 3558 were particularly effective, with an IC50 of 400 pM. In all cases, A(3) receptor stimulation inhibited only 30-50% of the calcium rise. In summary, stimulation of the A(3) adenosine receptor by either endogenous or synthesized agonists can limit the calcium rise accompanying NMDA receptor activation. it remains to be determined if partial block of the calcium rise by A(3) agonists can modify downstream responses to NMDA receptor stimulation. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Lu, Wennan; Lim, Jason; Mitchell, Claire H.] Univ Penn, Dept Physiol, Sch Med, Philadelphia, PA 19104 USA. [Zhang, Mei; Hu, Huiling; Laties, Alan M.] Univ Penn, Dept Ophthalmol, Sch Med, Philadelphia, PA 19104 USA. [Mitchell, Claire H.] Univ Penn, Dept Anat & Cell Biol, Sch Dent Med, Philadelphia, PA 19104 USA. [Hu, Huiling; Zhang, Xiulan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China. [Eysteinsson, Thor] Univ Iceland, Dept Physiol, Reykjavik, Iceland. [Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Mitchell, CH (reprint author), Univ Penn, Dept Physiol, Sch Med, 3700 Hamilton Walk, Philadelphia, PA 19104 USA. EM chm@mail.med.upenn.edu RI Jacobson, Kenneth/A-1530-2009; Eysteinsson, Thor /L-3069-2015 OI Jacobson, Kenneth/0000-0001-8104-1493; Eysteinsson, Thor /0000-0002-9748-5854 FU NIH [EY015537, EY013434]; Vision Research Core [EY001583]; Research to Prevent Blindness; Paul and Evanina Bell Mackall Foundation Trust; Jody Sack Fund; National Natural Science Foundation of China [30872831]; NIDDK, NIH, Bethesda, MD FX This work is supported by grants from the NIH EY015537 and EY013434 (CHM), Vision Research Core Grant EY001583 (CHM and AML), Research to Prevent Blindness (AML), the Paul and Evanina Bell Mackall Foundation Trust (AML), the Jody Sack Fund (HH, MZ and XZ), the National Natural Science Foundation of China 30872831 (XZ), and by support from the Intramural Research Program of NIDDK, NIH, Bethesda, MD (KAJ). The authors would like to thank Mortimer Civan for useful discussions and William Baldridge for assistance with the ganglion cell panning. NR 46 TC 23 Z9 23 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JAN PY 2010 VL 56 IS 1 BP 35 EP 41 DI 10.1016/j.neuint.2009.08.011 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 569JZ UT WOS:000275593700006 PM 19723551 ER PT J AU Schraml, FV Beason-Held, LL AF Schraml, Frank V. Beason-Held, Lori L. TI Technetium-99m ethyl cysteinate dimer (ECD) cerebral accumulation and symptom and sign severity during hypothyroidism SO NEUROENDOCRINOLOGY LETTERS LA English DT Article DE hypothyroidism; brain; single photon emission computed tomography (SPECT); neuropsychological; depression; thyroid stimulating hormone (TSH) ID BLOOD-FLOW; TRANSIENT HYPOTHYROIDISM; DEPRESSION; DISORDER; MOOD; DYSFUNCTION; TOMOGRAPHY; METABOLISM; ANXIETY AB OBJECTIVE: The purpose of this study was to correlate hypothyroid-related symptomatology with regional cerebral blood flow (rCBF) during hypothyroidism. MATERIALS AND METHODS: Nine thyroidectomized patients underwent neuropsychological testing and single photon emission computed tomography (SPECT) of their brains with technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), a lipophilic cerebral blood flow radiotracer, while hypothyroid, and again following thyroid hormone replacement. Neuropsychological test scores and TSH levels while hypothyroid were correlated with rCBF in hypothyroid-affected areas of the brain. RESULTS: Correlations were found during hypothyroidism between the noted parameters and ECD radiotracer accumulation in the following respective regions, all of which demonstrated hypothyroid-related cerebral blood flow (CBF) aberrations: TSH and left middle occipital gyrus; psychomotor performance speed and left precentral gyrus; and depression and right middle frontal gyrus, left middle frontal gyrus, right insula, and left thalamus. CONCLUSIONS: Severity of psychomotor impairment and depression, and TSH level during hypothyroidism appeared to correlate with CBF to brain regions associated with motor activity, mood and vision, respectively; and previously shown to manifest significantly altered rCBF during hypothyroidism. C1 [Schraml, Frank V.] St Josephs Hosp, Dept Radiol, Phoenix, AZ USA. [Schraml, Frank V.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Beason-Held, Lori L.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP Schraml, FV (reprint author), St Josephs Hosp, Dept Radiol, 350 W Thomas Rd, Phoenix, AZ USA. EM fvschraml@yahoo.com FU Dupont Industries; NIH, National Institute on Aging FX This study was supported in part by a grant from Dupont Industries. Dr. Beason-Held's work was supported by the Intramural Research Program of the NIH, National Institute on Aging. The opinions expressed in this work are those of the authors, and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. government. NR 25 TC 6 Z9 7 U1 1 U2 2 PU MAGHIRA & MAAS PUBLICATIONS PI STOCKHOLM PA PO BOX 26132, S-100 41 STOCKHOLM, SWEDEN SN 0172-780X J9 NEUROENDOCRINOL LETT JI Neuroendocrinol. Lett. PY 2010 VL 31 IS 1 BP 161 EP 167 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 737PY UT WOS:000288581900024 PM 20150864 ER PT S AU Smith, LK Cidlowski, JA AF Smith, Lindsay K. Cidlowski, John A. BE Martini, L Chrousos, GP Labrie, F Pacak, K Pfaff, DW TI Glucocorticoid-induced apoptosis of healthy and malignant lymphocytes SO NEUROENDOCRINOLOGY: PATHOLOGICAL SITUATIONS AND DISEASES SE Progress in Brain Research LA English DT Review; Book Chapter DE glucocorticoid; apoptosis; lymphocyte; haematological malignancy; glucocorticoid resistance ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NF-KAPPA-B; INDUCED THYMOCYTE APOPTOSIS; MULTIPLE-MYELOMA CELLS; DEXAMETHASONE-INDUCED APOPTOSIS; RECEPTOR MESSENGER-RNA; DNA-BINDING DOMAIN; HIGH-DOSE METHYLPREDNISOLONE; CELLULAR-DRUG RESISTANCE; NON-HODGKINS-LYMPHOMA AB Glucocorticoids exert a wide range of physiological effects, including the induction of apoptosis in lymphocytes. The progression of glucocorticoid-induced apoptosis is a multi-component process requiring contributions from both genomic and cytoplasmic signaling events. There is significant evidence indicating that the transactivation activity of the glucocorticoid receptor is required for the initiation of glucocorticoid-induced apoptosis. However, the rapid cytoplasmic effects of glucocorticoids may also contribute to the glucocorticoid-induced apoptosis-signaling pathway. Endogenous glucocorticoids shape the T-cell repertoire through both the induction of apoptosis by neglect during thymocyte maturation and the antagonism of T-cell receptor (TCR)-induced apoptosis during positive selection. Owing to their ability to induce apoptosis in lymphocytes, synthetic glucocorticoids are widely used in the treatment of haematological malignancies. Glucocorticoid chemotherapy is limited, however, by the emergence of glucocorticoid resistance. The development of novel therapies designed to overcome glucocorticoid resistance will dramatically improve the efficacy of glucocorticoid therapy in the treatment of haematological malignancies. C1 [Smith, Lindsay K.; Cidlowski, John A.] NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU Intramural NIH HHS [Z01 ES090079-12] NR 253 TC 25 Z9 27 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53616-7 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2010 VL 182 BP 1 EP 30 DI 10.1016/S0079-6123(10)82001-1 PG 30 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA BTR40 UT WOS:000287858500001 PM 20541659 ER PT S AU Kantorovich, V Pacak, K AF Kantorovich, Vitaly Pacak, Karel BE Martini, L Chrousos, GP Labrie, F Pacak, K Pfaff, DW TI Pheochromocytoma and paraganglioma SO NEUROENDOCRINOLOGY: PATHOLOGICAL SITUATIONS AND DISEASES SE Progress in Brain Research LA English DT Review; Book Chapter DE pheochromocytoma; paraganglioma; catecholamines; metanephrines; positron emission tomography ID MULTIPLE ENDOCRINE NEOPLASIA; VONHIPPEL-LINDAU DISEASE; VESICULAR MONOAMINE TRANSPORTER; TAKOTSUBO CONTRACTILE PATTERN; POSITRON-EMISSION-TOMOGRAPHY; MEDULLARY THYROID-CARCINOMA; DEHYDROGENASE SUBUNIT-B; TUMOR-SUPPRESSOR GENE; GERM-LINE MUTATIONS; MALIGNANT PHEOCHROMOCYTOMA AB Pheochromocytoma is a very special kind of tumor full of duplicity. On the one hand it represents its own microworld with unique clinical, biochemical and pathological features, while on the other it constitutes a tremendously significant part of whole body system, playing a vital role for practically every organ system. It has a very special character - sometimes like a child it can be sweet and predictable, while at times it can behave like a deadly wild beast, crashing and tearing everything on its path in a fierce rage. It also consists of the amazingly intelligent neuroendocrine cells that possess a magical ability to make miraculous substances of many kinds. But most of all, it is a system that is able to drive our curiosity and the itch of "Cogito, ergo sum" to limitless depths and year by year it still amazes us with new and unexpected discoveries that move our understanding of multiple pathways and metabolic events closer to the ultimate truth. Recent discoveries of succinate dehydrogenase (SHD) and prolyl hydroxylase (PHD) mutations, for example, propelled our understanding of neuroendocrine tumorigenesis as a whole, as well as physiology of mitochondrial respiratory chain and phenomenon of pseudohypoxia in particular. Good old discoveries make their way from dusty repositories to shine with new meaning, appropriate for the current level of knowledge. This acquired wisdom makes us better physicians knowing the specific expression makeup of catecholamine transporters, GLUTs and SRIFs allows for better tailored imaging and therapeutic manipulations. There are still long ways to go, keeping in mind that pheochromocytoma is but so very special, and we are optimistic and expect many great things to come. C1 [Pacak, Karel] NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Kantorovich, Vitaly] Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Div Endocrinol & Metab, Dept Internal Med,Coll Med, Little Rock, AR 72205 USA. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Intramural NIH HHS [Z01 HD008735-08] NR 226 TC 17 Z9 18 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53616-7 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2010 VL 182 BP 343 EP 373 DI 10.1016/S0079-6123(10)82015-1 PG 31 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA BTR40 UT WOS:000287858500015 PM 20541673 ER PT J AU Baade, PD Hernandez, EH Freedman, DM Smithers, BM Fritschi, L AF Baade, Peter D. Hernandez, Elena Herrero Freedman, D. Michal Smithers, B. Mark Fritschi, Lin TI No Role for Melanoma Treatment in the Association between Melanoma and Amyotrophic Lateral Sclerosis or Parkinson's Disease SO NEUROEPIDEMIOLOGY LA English DT Article ID TRPM7 C1 [Baade, Peter D.] Canc Council Queensland, Viertel Ctr Res Canc Control, Spring Hill, Qld 4001, Australia. [Baade, Peter D.] Queensland Univ Technol, Sch Publ Hlth, Brisbane, Qld 4001, Australia. [Smithers, B. Mark] Univ Queensland, Princess Alexandra Hosp, Dept Surg, Brisbane, Qld, Australia. [Smithers, B. Mark] Univ Queensland, Princess Alexandra Hosp, Queensland Melanoma Project, Brisbane, Qld, Australia. [Fritschi, Lin] Univ Western Australia, Western Australian Inst Med Res, Perth, WA 6009, Australia. [Freedman, D. Michal] NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hernandez, Elena Herrero] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. RP Baade, PD (reprint author), Canc Council Queensland, Viertel Ctr Res Canc Control, POB 201, Spring Hill, Qld 4001, Australia. EM peterbaade@cancerqld.org.au RI Fritschi, Lin /K-2096-2012; OI Fritschi, Lin /0000-0002-7692-3560; Baade, Peter/0000-0001-8576-8868 NR 10 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2010 VL 35 IS 4 BP 303 EP 304 DI 10.1159/000321177 PG 2 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 683AM UT WOS:000284444100011 PM 20962539 ER PT J AU Tooze, JA Gaussoin, SA Resnick, SM Fischbein, NJ Robinson, JG Bryan, RN An, Y Espeland, MA AF Tooze, Janet A. Gaussoin, Sarah A. Resnick, Susan M. Fischbein, Nancy J. Robinson, Jennifer G. Bryan, R. Nick An, Yang Espeland, Mark A. CA Women's Hlth Initiative Memory Stu TI A Uniform Approach to Modeling Risk Factor Relationships for Ischemic Lesion Prevalence and Extent: The Women's Health Initiative Magnetic Resonance Imaging Study SO NEUROEPIDEMIOLOGY LA English DT Article DE Statistical methods; Brain magnetic resonance imaging; Cognition; Women's health ID WHITE-MATTER LESIONS; POSTMENOPAUSAL HORMONE-THERAPY; SILENT BRAIN INFARCTS; SMALL-VESSEL DISEASE; WHIMS-MRI; COGNITIVE DECLINE; ROTTERDAM SCAN; PROGRESSION; MEMORY; SEGMENTATION AB Background: Both the prevalence and extent of brain magnetic resonance imaging (MRI) abnormalities are related to risk factors for dementia. Typically these associations have been explored separately, but an integrated modeling approach would allow the separate relationships to be consistently described and contrasted. Methods: Region-specific measures of ischemic lesion volumes were obtained from standardized brain MRI from 1,403 women enrolled in the Women's Health Initiative hormone therapy trials. Mixed-effects mixed-distribution models were fitted to explore jointly the relationships that the region-specific prevalence of ischemic lesions and region-specific ischemic lesion volumes had with risk factors and scores from tests of cognitive function. Results: Women with greater probabilities (prevalence) of having ischemic lesions in brain regions also tended to have larger volumes (extent) of ischemic lesions within the affected regions (p < 0.001). Across the 5 regions included in analyses (frontal, limbic, occipital, parietal and temporal), prevalence and extent varied (p < 0.001). Each was increased among women who were older, had hypertension or who had previously been classified as cognitively impaired (p < 0.01). Additionally, extent was significantly increased among women with a history of smoking (p = 0.02). Cognitive function tests were more strongly related to the extent than prevalence of ischemic lesions and relationships varied among cognitive domains (p < 0.001). Conclusions: Mixed-effects mixed-distribution models provide a coherent basis for examining relationships involving the prevalence and extent of ischemic brain lesions. Across the cohort and regions we examined, relationships with risk factors and cognitive function appeared to be stronger for extent than for prevalence. Copyright (C) 2009 S. Karger AG, Basel C1 [Tooze, Janet A.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Resnick, Susan M.] NIA, Lab Personal & Cognit 03, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [An, Yang] MedStar Res Inst, Baltimore, MD USA. [Fischbein, Nancy J.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Robinson, Jennifer G.] Univ Iowa, Lipid Res Clin, Dept Epidemiol, Iowa City, IA USA. [Robinson, Jennifer G.] Univ Iowa, Lipid Res Clin, Dept Med, Iowa City, IA USA. [Bryan, R. Nick] Univ Penn Hlth Syst, Dept Radiol, Philadelphia, PA USA. RP Tooze, JA (reprint author), Wake Forest Univ Hlth Sci, Dept Biostat Sci, Div Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jtooze@wfubmc.edu FU Wyeth Pharmaceuticals Inc., St. Davids, Pa., USA; National Heart, Lung and Blood Institute; WHI Magnetic Resonance Imaging Study; National Heart, Lung and Blood Institute of the National Institutes of Health; US Department of Health and Human Services; Department of Health and Human Services; National Institute on Aging [N01-AG-9-2115]; National Institutes of Health, Bethesda, Md., USA; National Institutes of Health; Medstar Research Institute FX The WHI Memory Study was initially funded by Wyeth Pharmaceuticals Inc., St. Davids, Pa., USA, with sustaining support from the National Heart, Lung and Blood Institute, which also funded the WHI Magnetic Resonance Imaging Study. The WHI is funded by the National Heart, Lung and Blood Institute of the National Institutes of Health, US Department of Health and Human Services. Wyeth Pharmaceuticals provided the study drug and the placebo to the WHI trial. The WHI Study of Cognitive Aging was supported by the Department of Health and Human Services and the National Institute on Aging, N01-AG-9-2115, National Institutes of Health, Bethesda, Md., USA. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging; a portion of that support was through an R&D contract with Medstar Research Institute. NR 32 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2010 VL 34 IS 1 BP 55 EP 62 DI 10.1159/000260071 PG 8 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 530MY UT WOS:000272598200009 PM 19940514 ER PT J AU Gunstad, J Lhotsky, A Wendell, CR Ferrucci, L Zonderman, AB AF Gunstad, John Lhotsky, April Wendell, Carrington Rice Ferrucci, Luigi Zonderman, Alan B. TI Longitudinal Examination of Obesity and Cognitive Function: Results from the Baltimore Longitudinal Study of Aging SO NEUROEPIDEMIOLOGY LA English DT Article DE Obesity; Cognition; Aged; Longitudinal; Age-associated cognitive change ID BODY-MASS INDEX; VASCULAR RISK-FACTORS; HEALTHY OLDER-ADULTS; ALZHEIMER-DISEASE; UNITED-STATES; ABDOMINAL OBESITY; FAT DISTRIBUTION; FOLLOW-UP; WOMEN; WEIGHT AB Background: Obesity indices (i.e. BMI, waist-to-hip ratio) show differential relationships to other health outcomes, though their association to neurocognitive outcome is unclear. Methods: We examined whether central obesity would be more closely associated with cognitive function in 1,703 participants from the Baltimore Longitudinal Study of Aging. Results: Longitudinal mixed-effects regression models showed multiple obesity indices were associated with poorer performance in a variety of cognitive domains, including global screening measures, memory, and verbal fluency tasks. Obesity was associated with better performance on tests of attention and visuospatial ability. An obesity index by age interaction emerged in multiple domains, including memory and attention/executive function. Conclusion: Obesity indices showed similar associations to cognitive function, and further work is needed to clarify the physiological mechanisms that link obesity to poor neurocognitive outcome. Copyright (C) 2010 S. Karger AG, Basel C1 [Gunstad, John] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Gunstad, John] Summa Hlth Syst, Dept Psychiat, Akron, OH USA. [Lhotsky, April; Wendell, Carrington Rice; Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Bethesda, MD 20892 USA. RP Gunstad, J (reprint author), Kent State Univ, Dept Psychol, 221 Kent Hall, Kent, OH 44242 USA. EM jgunstad@kent.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institutes of Health; [DK075119]; [HL089311] FX The National Institute on Aging (NIA) Intramural Research Program of the National Institutes of Health supported this research. Members of NIA are authors on this paper and were involved in the planning and writing of this paper. Manuscript preparation was also partly funded by DK075119 and HL089311 (J.G.). NR 55 TC 95 Z9 97 U1 11 U2 28 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2010 VL 34 IS 4 BP 222 EP 229 DI 10.1159/000297742 PG 8 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 574CW UT WOS:000275967100005 PM 20299802 ER PT J AU Tiemeier, H Lenroot, RK Greenstein, DK Tran, L Pierson, R Giedd, JN AF Tiemeier, Henning Lenroot, Rhoshel K. Greenstein, Deanna K. Tran, Lan Pierson, Ronald Giedd, Jay N. TI Cerebellum development during childhood and adolescence: A longitudinal morphometric MRI study SO NEUROIMAGE LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HUMAN BRAIN; COGNITIVE-DEVELOPMENT; PREFRONTAL CORTEX; SYNAPTIC DENSITY; METAANALYSIS; AUTISM; ABNORMALITY; EXPRESSION; VOLUMETRY AB In addition to its well-established role in balance, coordination, and other motor skills, the cerebellum is increasingly recognized as a prominent contributor to a wide array of cognitive and emotional functions. Many of these capacities undergo dramatic changes during childhood and adolescence. However, accurate characterization of co-occurring anatomical changes has been hindered by lack of longitudinal data and methodologic challenges in quantifying subdivisions of the cerebellum. In this study we apply an innovative image analysis technique to quantify total cerebellar volume and 11 subdivisions (i.e. anterior, superior posterior, and inferior posterior lobes, Corpus medullare, and three vermal regions) from anatomic brain MRI scans from 25 healthy females and 25 healthy males aged 5-24 years, each of whom was scanned at least three times at approximately 2-year intervals. Total cerebellum volume followed an inverted U shaped developmental trajectory peaking at age 11.8 years in females and 15.6 years in males. Cerebellar volume was 10% to 13% larger in males depending on the age of comparison and the sexual dimorphism remained significant after covarying for total brain volume. Subdivisions of the cerebellum had distinctive developmental trajectories with more phylogenetically recent regions maturing particularly late. The cerebellum's unique protracted developmental trajectories, sexual dimorphism, preferential vulnerability to environmental influences, and frequent implication in childhood onset disorders such as autism and ADHD make it a prime target for pediatric neuroimaging investigations. (c) 2009 Elsevier Inc. All rights reserved. C1 [Tiemeier, Henning; Lenroot, Rhoshel K.; Greenstein, Deanna K.; Tran, Lan; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Tiemeier, Henning] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands. [Pierson, Ronald] Univ Iowa, Sch Med, Dept Psychiat, Iowa City, IA 52242 USA. RP Tiemeier, H (reprint author), Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, POB 2060, NL-3000 CB Rotterdam, Netherlands. EM h.tiemeier@erasmusmc.nl RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Tiemeier, Henning/0000-0002-4395-1397 FU National Institute of Mental Health FX Dr. H. Tiemeier's work on this project was supported by a research fellowship of the Sophia Stichting (2004-025/SWO). This study was funded by the Intramural Program of the National Institute of Mental Health. NR 55 TC 127 Z9 129 U1 2 U2 17 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 1 PY 2010 VL 49 IS 1 BP 63 EP 70 DI 10.1016/j.neuroimage.2009.08.016 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 522WV UT WOS:000272031700007 PM 19683586 ER PT J AU Tanji, K Leopold, DA Ye, FQ Zhu, C Malloy, M Saunders, RC Mishkin, M AF Tanji, Kazuyo Leopold, David A. Ye, Frank Q. Zhu, Charles Malloy, Megan Saunders, Richard C. Mishkin, Mortimer TI Effect of sound intensity on tonotopic fMRI maps in the unanesthetized monkey SO NEUROIMAGE LA English DT Article DE Tonotopy; fMRI; Auditory cortex; Lateral inhibition; Negative BOLD ID LEVEL-DEPENDENT REPRESENTATION; PRIMARY AUDITORY-CORTEX; MACAQUE MONKEYS; FUNCTIONAL MRI; SCANNER NOISE; FREQUENCY; ACTIVATION; FIELDS; BRAIN; ORGANIZATION AB The monkey's auditory cortex includes a core region on the supratemporal plane (STP) made up of the tonotopically organized areas A1, R, and RT together with a surrounding belt and a lateral parabelt region, The functional studies that yielded the tonotopic maps and corroborated the anatomical division into core, belt, and parabelt typically used low-amplitude Pure tones that were often restricted to threshold-level intensities. Here we used functional magnetic resonance imaging in awake rhesus monkeys to determine whether, and if so how, the tonotopic maps and the pattern of activation in core, belt, and parabelt are affected by systematic changes in sound intensity. Blood oxygenation level-dependent (BOLD) responses to groups of low- and high-frequency pure tones 3-4 octaves apart were measured at multiple sound intensity levels. The results revealed tonotopic maps in the auditory core that reversed at the putative areal boundaries between A1 and R and between R and RT. Although these reversals of the tonotopic representations were present at all intensity levels, the lateral spread of activation depended on sound amplitude, with increasing recruitment of the adjacent belt areas as the intensities increased. Tonotopic organization along the STP was also evident in frequency-specific deactivation (i.e. "negative BOLD"), an effect that was intensity-specific as well. Regions of positive and negative BOLD were spatially interleaved, possibly reflecting lateral inhibition of high-frequency areas during activation of adjacent low-frequency areas, and vice versa. These results, which demonstrate the strong influence of tonal amplitude on activation levels, identify sound intensity as an important adjunct parameter for mapping the functional architecture of auditory cortex. (c) 2009 Elsevier Inc. All rights reserved. C1 [Tanji, Kazuyo; Leopold, David A.; Malloy, Megan; Saunders, Richard C.; Mishkin, Mortimer] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Ye, Frank Q.; Zhu, Charles] NIMH, Neurophysiol Imaging Facil, NINDS, NEI,US Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tanji, K (reprint author), Yamagata Univ, Dept Clin Neurosci, 2-2-2 Iida Nishi, Yamagata 9909585, Japan. EM tanjik@med.id.yamagata-u.ac.jp OI Leopold, David/0000-0002-1345-6360 FU Intramural NIH HHS [Z99 MH999999] NR 28 TC 29 Z9 29 U1 0 U2 9 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 1 PY 2010 VL 49 IS 1 BP 150 EP 157 DI 10.1016/j.neuroimage.2009.07.029 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 522WV UT WOS:000272031700017 PM 19631273 ER PT J AU Lee, J Hirano, Y Fukunaga, M Silva, AC Duyn, JH AF Lee, Jongho Hirano, Yoshiyuki Fukunaga, Masaki Silva, Afonso C. Duyn, Jeff H. TI On the contribution of deoxy-hemoglobin to MRI gray-white matter phase contrast at high field SO NEUROIMAGE LA English DT Article DE Phase contrast image; Deoxy-hemoglobin; High field; USPIO; Iron oxide nano-particle ID BLOOD-VOLUME; IMAGING SWI; HUMAN BRAIN; SUSCEPTIBILITY; IMAGES; BOLD; FMRI; VOLUNTEERS; DEPENDENCE; VESSELS AB High field (>= 7 T) MRI Studies based on signal phase have been used to improve visualization of the fine structure of the brain, most notably the major white matter fiber bundles, the gray-white matter Subdivision, and the laminar cortical architecture. The observed contrast has been attributed in part to local variations in magnetic susceptibility arising from iron in storage proteins and tissue lipid. Another contribution could come from the paramagnetic blood constituent deoxy-hemoglobin, the tissue concentration of which may vary through local variations in vascular density. To investigate this possibility, we examined phase contrast between gray and white matter in rats after intravenous administration Of a superparamagnetic contrast agent at various dosages. At the maximum dosage (3 mg Fe/kg), which resulted in all estimated paramagnetic susceptibility shift 4-8 times larger than deoxy-hemoglobin, we observed a negligible increase in phase contrast between gray and white matter. This result suggests that endogenous deoxy-hemoglobin has no significant contribution to phase contrast between gray and white matter. Published by Elsevier Inc. C1 [Lee, Jongho; Fukunaga, Masaki; Duyn, Jeff H.] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Hirano, Yoshiyuki; Silva, Afonso C.] NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), 9000 Rockville Pike,Bldg 10,Room B1D723A, Bethesda, MD 20892 USA. EM jonghoyi@mail.nih.gov RI Duyn, Jozef/F-2483-2010; Silva, Afonso/A-7129-2009; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 FU Intramural NIH HHS [Z99 NS999999] NR 35 TC 43 Z9 43 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2010 VL 49 IS 1 BP 193 EP 198 DI 10.1016/j.neuroimage.2009.07.017 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 522WV UT WOS:000272031700022 PM 19619663 ER PT J AU Jones, TB Bandettini, PA Kenworthy, L Case, LK Milleville, SC Martin, A Birn, RM AF Jones, Tyler B. Bandettini, Peter A. Kenworthy, Lauren Case, Laura K. Milleville, Shawn C. Martin, Alex Birn, Rasmus M. TI Sources of group differences in functional connectivity: An investigation applied to autism spectrum disorder SO NEUROIMAGE LA English DT Article ID RESTING-STATE NETWORKS; INFERIOR FRONTAL-CORTEX; DEFAULT MODE; HUMAN BRAIN; FMRI DATA; SENTENCE COMPREHENSION; EXECUTIVE DYSFUNCTION; MULTIPLE-SCLEROSIS; TEMPORAL-LOBE; GLOBAL SIGNAL AB An increasing number of fMRI studies are using the correlation of low-frequency fluctuations between brain regions, believed to reflect synchronized variations in neuronal activity, to infer "functional connectivity". In studies of autism spectrum disorder (ASD), decreases in this measure of connectivity have been found by focusing on the response to task modulation, by using only the rest periods, or by analyzing purely resting-state data. This difference in connectivity, however, could result from a number of different mechanisms differences in noise, task-related fluctuations, task performance, or spontaneous neuronal activity. In this Study, we investigate the difference in functional connectivity between adolescents with high-functioning ASD and typically developing control subjects by examining the residual fluctuations occurring on top of the fMRI response to an overt verbal fluency task. We find decreased correlations of these residuals (a decreased "connectivity") in ASD subjects. Furthermore, we find that this decrease was not due to task-related effects, block-to-block variations in task performance, or increased noise, and the difference was greatest when primarily rest periods are considered. These findings suggest that the estimate of disrupted functional connectivity in ASD is likely driven by differences in task-unrelated neuronal fluctuations. (C) Published by Elsevier Inc. C1 [Jones, Tyler B.; Bandettini, Peter A.; Kenworthy, Lauren; Case, Laura K.; Milleville, Shawn C.; Martin, Alex; Birn, Rasmus M.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA. RP Birn, RM (reprint author), Univ Wisconsin Madison, Dept Psychiat, 6001 Res Pk Blvd, Madison, WI 53719 USA. EM rbirn@wisc.edu RI martin, alex/B-6176-2009; OI Case, Laura/0000-0003-3730-2451 FU National Institute of Mental Health FX This research was supported by the Intramural Research Program of the National Institute of Mental Health. The authors thank Dr. Gregory Wallace for providing information on clinical assessment and diagnosis. NR 73 TC 85 Z9 85 U1 5 U2 18 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 1 PY 2010 VL 49 IS 1 BP 401 EP 414 DI 10.1016/j.neuroimage.2009.07.051 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 522WV UT WOS:000272031700042 PM 19646533 ER PT J AU Knight, DC Waters, NS King, MK Bandettini, PA AF Knight, David C. Waters, Najah S. King, Margaret K. Bandettini, Peter A. TI Learning-related diminution of unconditioned SCR and fMRI signal responses SO NEUROIMAGE LA English DT Article ID VENTROMEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; HUMAN AMYGDALA ACTIVITY; EXTINCTION MEMORY; FUNCTIONAL MRI; FEAR RESPONSES; HUMANS; AWARENESS; ACTIVATION; EXPRESSION AB During Pavlovian conditioning the expression of a conditioned response is typically taken as evidence that an association between a conditioned stimulus (CS) and an unconditioned stimulus (UCS) has been formed. However, learning-related changes in the unconditioned response (UCR) produced by a predictable UCS can also develop. Learning-related reductions in UCR magnitude are often referred to as UCR diminution. In the present study, we examined UCR diminution in the functional magnetic resonance imaging (fMRI) signal by pairing supra- and sub-threshold CS presentations with a UCS. UCR diminution was observed within several brain regions associated with fear learning and memory including the insula, inferior parietal lobe, ventromedial prefrontal cortex (PFC), dorsomedial PFC, and dorsolateral PFC. CS perception appeared to mediate UCR diminution within the ventromedial PFC and posterior cingulate cortex. UCRs within these regions were larger when the UCS followed an unperceived compared to a perceived CS. UCS expectancies appeared to modulate UCRs within the dorsomedial PFC, dorsolateral PFC, insula, and inferior parietal lobe. Activity within these regions showed an inverse relationship with participants' UCS expectancies, Such that as UCS expectancy increased UCR magnitude decreased. in addition, activity within the dorsomedial PFC, dorsolateral PFC, and insula showed a linear relationship with unconditioned skin conductance response (SCR) expression. These findings demonstrate UCR diminution within the fMRI signal, and suggest that UCS expectancies modulate prefrontal cortex responses to aversive stimuli. In turn, prefrontal cortex activity appears to modulate the expression of unconditioned SCRs. Published by Elsevier Inc. C1 [Knight, David C.; Waters, Najah S.; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Knight, David C.; King, Margaret K.] Univ Alabama, Dept Psychol, Civitan Int Res Ctr, Birmingham, AL 35294 USA. RP Knight, DC (reprint author), CIRC 235H,1530 3rd AVE S, Birmingham, AL 35294 USA. EM knightdc@uab.edu FU National Institute of Mental Health; NIH FX This research was supported by the Intramural Research Program of the National Institute of Mental Health, NIH. NR 35 TC 25 Z9 25 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2010 VL 49 IS 1 BP 843 EP 848 DI 10.1016/j.neuroimage.2009.07.012 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 522WV UT WOS:000272031700083 PM 19616105 ER PT J AU Birn, RM Kenworthy, L Case, L Caravella, R Jones, TB Bandettin, PA Martin, A AF Birn, Rasmus M. Kenworthy, Lauren Case, Laura Caravella, Rachel Jones, Tyler B. Bandettin, Peter A. Martin, Alex TI Neural systems supporting lexical search guided by letter and semantic category cues: A self-paced overt response fMRI study of verbal fluency SO NEUROIMAGE LA English DT Article ID INFERIOR FRONTAL GYRUS; WORD FORM AREA; ALZHEIMERS-DISEASE; DESIGN FLUENCY; HUNTINGTONS-DISEASE; PREFRONTAL CORTEX; BRAIN ACTIVATION; RIGHT-HEMISPHERE; WORKING-MEMORY; LOBE LESIONS AB Verbal fluency tasks have been widely. used to evaluate language and executive control processes in the human brain. FMRI studies of verbal fluency, however, have used either silent word generation (which provides no behavioral measure) or cued generation of single words in order to contend with speech-related motion artifacts. In this study, we use a recently developed paradigm design to investigate the neural correlates of verbal fluency during overt, free recall, word generation so that performance and brain activity could be evaluated under conditions that more closely mirror standard behavioral test demands. We investigated verbal fluency to both letter and category cues in order to evaluate differential involvement of specific frontal and temporal lobe sites as a function of retrieval cue type, as suggested by previous neuropsychological and neuroimaging investigations. in addition, we incorporated both a task switching manipulation and an automatic speech condition in order to modulate the demand placed on executive functions. We found greater activation in the left hemisphere during category and letter fluency tasks, and greater right hemisphere activation during automatic speech. We also found that letter and category fluency tasks were associated with differential involvement of specific regions of the frontal and temporal lobes. These findings provide converging evidence that letter and category fluency performance is dependent on partially distinct neural circuitry. They also provide strong evidence that verbal fluency can be successfully evaluated in the MR environment using overt, self-paced, responses. Published by Elsevier Inc. C1 [Birn, Rasmus M.; Kenworthy, Lauren; Case, Laura; Caravella, Rachel; Jones, Tyler B.; Bandettin, Peter A.; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA. RP Birn, RM (reprint author), Univ Wisconsin, Dept Psychiat, 6001 Res Pk Blvd, Madison, WI 53719 USA. EM rbirn@wisc.edu RI martin, alex/B-6176-2009; OI Case, Laura/0000-0003-3730-2451; Caravella, Rachel/0000-0003-1136-5913 FU National Institute of Mental Health FX This research was Supported by the Intramural Research Program of the National Institute of Mental Health. NR 54 TC 117 Z9 120 U1 7 U2 21 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 1 PY 2010 VL 49 IS 1 BP 1099 EP 1107 DI 10.1016/j.neuroimage.2009.07.036 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 522WV UT WOS:000272031700111 PM 19632335 ER PT J AU Marques, AH Silverman, MN Sternberg, EM AF Marques, Andrea H. Silverman, Marni N. Sternberg, Esther M. TI Evaluation of Stress Systems by Applying Noninvasive Methodologies: Measurements of Neuroimmune Biomarkers in the Sweat, Heart Rate Variability and Salivary Cortisol SO NEUROIMMUNOMODULATION LA English DT Article DE Cytokines; Neuropeptides; Cardiovascular system; HPA axis ID IMMUNITY; PATCHES; PLASMA; WOMEN AB The two main arms of the stress system include the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. These two neural stress systems coordinate the response of many other physiological systems to a stressor, including the immune and cardiovascular systems, bringing the body back to homeostasis. The nervous and immune systems communicate with each other in a bidirectional manner. In this review, we will discuss the use of noninvasive methods to evaluate the immune system, ANS and HPA axis. Collection of sweat and saliva, and measurement of heart rate variability are noninvasive methods that can be applied to evaluate neuroimmune interactions. Recently, we validated a new methodology to simultaneously evaluate a large array of neural and immune biomarkers in sweat, collected through cutaneous sweat patches and measured by recycling immunoaffinity chromatography. Noninvasive and ambulatory methodologies of biomarker collection can overcome several limitations intrinsic to invasive methods, such as reducing the stress triggered by collection itself and allowing a wider application to field and community-based settings. Ultimately, simultaneous evaluation of neural and immune systems with noninvasive techniques will help elucidate the underlying interactions of these systems and their role in disease susceptibility and progression of stress-related disorders. Copyright (C) 2010 S. Karger AG, Basel C1 [Sternberg, Esther M.] NIMH, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, NIH, 5625 Fishers Lane,MSC 9401,Rm 4N-13B, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov NR 9 TC 34 Z9 37 U1 1 U2 33 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2010 VL 17 IS 3 BP 205 EP 208 DI 10.1159/000258725 PG 4 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 552VS UT WOS:000274322300020 PM 20134204 ER PT J AU Fields, RD AF Fields, R. Douglas TI Central role of glia in disease research SO NEURON GLIA BIOLOGY LA English DT Editorial Material C1 NIH, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NIH, Nervous Syst Dev & Plast Sect, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA HD000713-16] NR 8 TC 1 Z9 1 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2010 VL 6 IS 2 BP 91 EP 92 DI 10.1017/S1740925X10000177 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 674XA UT WOS:000283782700001 PM 20959032 ER PT J AU Fields, RD AF Fields, R. Douglas TI Glutamate receptors: the cause or cure in perinatal white matter injury? SO NEURON GLIA BIOLOGY LA English DT Article DE Paraventricular leuckomalacia; cerebral palsy; hypoxia; premature infants; glutamate toxicity; axon-oligodendrocyte signalling; myelination AB Glutamate toxicity from hypoxia-ischaemia during the perinatal period causes white matter injury that can result in long-term motor and intellectual disability. Blocking ionotropic glutamate receptors (GluRs) has been shown to inhibit oligodendrocyte injury in vitro, but GluR antagonists have not yet proven helpful in clinical studies. The opposite approach of activating GluRs on developing oligodendrocytes shows promise in experimental studies on rodents as reported by Jartzie et al., in this issue. Group I metabotropic glutamate receptors (mGluRs) are expressed transiently on developing oligodendrocytes in humans during the perinatal period, and the blood-brain-barrier permeable agonist of group I mGluRs, 1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD), reduces white matter damage significantly in a rat model of perinatal hypoxia-ischaemia. The results suggest drugs activating this class of GluRs could provide a new therapeutic approach for preventing cerebral palsy and other neurological consequences of diffuse white matter injury in premature infants. C1 [Fields, R. Douglas] NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. [Fields, R. Douglas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov NR 25 TC 1 Z9 1 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2010 VL 6 IS 4 BP 209 EP 211 DI 10.1017/S1740925X11000147 PG 3 WC Neurosciences SC Neurosciences & Neurology GA V22EK UT WOS:000208258300001 PM 22217580 ER PT S AU O'Donovan, MJ Bonnot, A Mentis, GZ Chub, N Pujala, A Alvarez, FJ AF O'Donovan, Michael J. Bonnot, Agnes Mentis, George Z. Chub, Nikolai Pujala, Avinash Alvarez, Francisco J. BE ZiiskindConhaim, L Fetcho, JR Hochman, S MacDermott, AB Stein, PSG TI Mechanisms of excitation of spinal networks by stimulation of the ventral roots SO NEURONS AND NETWORKS IN THE SPINAL CORD SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Cellular and Network Functions in the Spinal Cord CY JUN 23-26, 2009 CL Univ Wisconsin, Pyle Ctr, Madison, WI HO Univ Wisconsin, Pyle Ctr DE calcium imaging; motoneuron; recurrent excitation; spinal cord ID METABOTROPIC GLUTAMATE RECEPTORS; VESICULAR GLUTAMATE; CENTRAL SYNAPSES; CORD; IDENTIFICATION; TRANSPORTER; MOTONEURONS; RAT; CIRCUITS; INHIBITION AB It has recently been demonstrated that motoneurons in neonatal rodents release an excitatory amino acid, in addition to acetylcholine, from their central terminals onto Renshaw cells. Although the function of this amino acid release is not understood, it may mediate the excitatory actions of motor axon stimulation on spinal motor networks. Stimulation of motor axons in the ventral roots or muscle nerves can activate the locomotor central pattern generator or entrain bursting in the disinhibited cord. Both of these effects persist in the presence of cholinergic antagonists and are abolished or diminished by ionotropic and metabotropic glutamate antagonists. Calcium imaging in the disinhibited cord shows that a ventral root stimulus evokes ventrolateral activity initially, which subsequently propagates to the rest of the cord. This finding suggests that excitatory interneurons excited by motoneuron recurrent collaterals are located in this region. However, motoneurons do not exhibit short latency excitatory potentials in response to ventral root stimulation indicating that the excitatory effects are mediated polysynaptically. We discuss the significance of these findings. C1 [O'Donovan, Michael J.; Mentis, George Z.; Chub, Nikolai; Pujala, Avinash] NINDS, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP O'Donovan, MJ (reprint author), Bldg 35,Room 3C-1014,35 Convent Dr, Bethesda, MD 20892 USA. EM odonovm@ninds.nih.gov RI o'donovan, michael/A-2357-2015; Alvarez, Francisco/H-4929-2011 OI o'donovan, michael/0000-0003-2487-7547; FU NINDS FX This work was supported by the intramural program of NINDS. NR 25 TC 12 Z9 12 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-778-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1198 BP 63 EP 71 DI 10.1111/j.1749-6632.2010.05535.x PG 9 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BQO12 UT WOS:000281413900007 PM 20536921 ER PT S AU Mentis, GZ Alvarez, FJ Shneider, NA Siembab, VC O'Donovan, MJ AF Mentis, George Z. Alvarez, Francisco J. Shneider, Neil A. Siembab, Valerie C. O'Donovan, Michael J. BE ZiiskindConhaim, L Fetcho, JR Hochman, S MacDermott, AB Stein, PSG TI Mechanisms regulating the specificity and strength of muscle afferent inputs in the spinal cord SO NEURONS AND NETWORKS IN THE SPINAL CORD SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Cellular and Network Functions in the Spinal Cord CY JUN 23-26, 2009 CL Univ Wisconsin, Pyle Ctr, Madison, WI HO Univ Wisconsin, Pyle Ctr DE proprioceptor; muscle spindle; motor neuron; Renshaw; stretch reflex ID SPINDLE-DERIVED NEUROTROPHIN-3; RECURRENT INHIBITION; SYNAPTIC CONNECTIVITY; SENSORY NEURONS; MOTOR-NEURONS; RAT; MOTONEURONS; SYNAPSES; PROPRIOCEPTION; RECEPTORS AB We investigated factors controlling the development of connections between muscle spindle afferents, spinal motor neurons, and inhibitory Renshaw cells. Several mutants were examined to establish the role of muscle spindles, muscle spindle-derived NT3, and excess NT3 in determining the specificity and strength of these connections. The findings suggest that although spindle-derived factors are not necessary for the initial formation and specificity of the synapses, spindle-derived NT3 seems necessary for strengthening homonymous connections between la afferents and motor neurons during the second postnatal week. We also found evidence for functional monosynaptic connections between sensory afferents and neonatal Renshaw cells although the density of these synapses decreases at P15. We conclude that muscle spindle synapses are weakened on Renshaw cells while they are strengthened on motor neurons. Interestingly, the loss of sensory synapses on Renshaw cells was reversed in mice overexpresssing NT3 in the periphery, suggesting that different levels of NT3 are required for functional maintenance and strengthening of spindle afferent inputs on motor neurons and Renshaw cells. C1 [Mentis, George Z.; Shneider, Neil A.; O'Donovan, Michael J.] NINDS, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Mentis, GZ (reprint author), Columbia Univ, Ctr Motor Neuron Biol & Dis, P&S Bldg,Room 4-450,630 W 168th St, New York, NY 10032 USA. EM gzmentis@columbia.edu RI o'donovan, michael/A-2357-2015; Alvarez, Francisco/H-4929-2011; OI o'donovan, michael/0000-0003-2487-7547; Shneider, Neil/0000-0002-3223-7366 FU NINDS; National Institutes of Health [NS047357] FX This work was supported by the intramural program of NINDS (G.Z.M., N.A.S. and M.J.O'D) and by the National Institutes of Health Grant NS047357 (F.J.A.). NR 40 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-778-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1198 BP 220 EP 230 DI 10.1111/j.1749-6632.2010.05538.x PG 11 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BQO12 UT WOS:000281413900023 PM 20536937 ER PT J AU Ait-Ali, D Stroth, N Sen, JM Eiden, LE AF Ait-Ali, Djida Stroth, Nikolas Sen, Jyoti M. Eiden, Lee E. TI PACAP-cytokine interactions govern adrenal neuropeptide biosynthesis after systemic administration of LPS SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Neuropharmacology Conference CY OCT 14-16, 2009 CL Chicago, IL DE PACAP; VIP; Galanin; Septic shock; Stress; LPS; TNF-alpha; Adrenal medulla; Adrenal cortex ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; VASOACTIVE-INTESTINAL-PEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; CHROMAFFIN CELLS; FACTOR-ALPHA; SUBSTANCE-P; NEUROENDOCRINE REGULATION; GENE-EXPRESSION; GALANIN AB We have examined induction of neuropeptide expression in adrenal medulla after treatment of mice with lipopolysaccharide (LPS), a model for septic shock, which activates both immune and stress responses in vivo. Messenger RNAs encoding vasoactive intestinal polypeptide (VIP) and galanin, both modulators of steroidogenesis in neighboring adrenal cortex, are up-regulated at 24 h (eight-fold for VIP and two-fold for galanin) after LPS injection, and remain elevated for the following 24 h. Up-regulation of VIP and galanin by LPS is abrogated in pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice, suggesting an interaction between LPS, or LPS-induced cytokines, and PACAP released in adrenal medulla from the splanchnic nerve. Treatment of cultured chromaffin cells with 100 nM PACAP and 10 nM tumor necrosis factor-alpha (TNF-alpha), a cytokine whose production is elevated by LPS, results in long-term synergistic up-regulation of VIP and galanin mRNA. PACAP blocks the earlier induction by TNF-alpha of mRNA encoding inhibitor of NF-kappa B alpha (I kappa B alpha), normally a negative autoregulator of TNF-alpha signaling through nuclear factor-kappa B (NF-kappa B), without affecting the induction of TNF-alpha-induced protein 3 (TNFAIP3), another NF-kappa B-dependent gene induced by TNF-alpha in chromaffin cells. By acting downstream of NF-kappa B to inhibit I kappa B alpha gene induction by TNF-alpha, PACAP may block I kappa B alpha-dependent negative autoregulation of TNF-alpha signaling through NF-kappa B, prolonging TNF-alpha-dependent signaling to neuropeptide-encoding genes in chromaffin cells. This mechanism may also underlie PACAP-dependent neuropeptide gene induction by LPS in vivo. Published by Elsevier Ltd. C1 [Ait-Ali, Djida; Stroth, Nikolas; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. [Sen, Jyoti M.] NIA, Lymphocyte Dev Unit, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bldg 49,Room 5A-38, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov OI Eiden, Lee/0000-0001-7524-944X FU Intramural NIH HHS [Z01 AG000772-01, Z01 MH002386-21, Z01 AG000768-04]; NIMH NIH HHS [Z01 MH002386] NR 40 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 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2010 VL 58 IS 1 BP 208 EP 214 DI 10.1016/j.neuropharm.2009.07.034 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 536NS UT WOS:000273051700027 PM 19647754 ER PT J AU Ide, S Sora, I Ikeda, K Minami, M Uhl, GR Ishihara, K AF Ide, Soichiro Sora, Ichiro Ikeda, Kazutaka Minami, Masabumi Uhl, George R. Ishihara, Kumatoshi TI Reduced emotional and corticosterone responses to stress in mu-opioid receptor knockout mice SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Neuropharmacology Conference CY OCT 14-16, 2009 CL Chicago, IL DE mu-Opioid receptor; Knockout mouse; Corticosterone; Stress; Anxiety; Depression ID PITUITARY-ADRENAL AXIS; MORPHINE-INDUCED ANALGESIA; ELEVATED PLUS-MAZE; FORCED SWIM TEST; LOCUS-COERULEUS; ENDOGENOUS OPIOIDS; RAT; IMMOBILITY; DELTA; SEX AB The detailed mechanisms of emotional modulation in the nervous system by opioids remain to be elucidated, although the opioid system is well known to play important roles in the mechanisms of analgesia and drug dependence. in the present study, we conducted behavioral tests of anxiety and depression and measured corticosterone concentrations in both male and female mu-opioid receptor knockout (MOP-KO) mice to reveal the involvement of mu-opioid receptors in stress-induced emotional responses. MCP-KO mice entered more and spent more time in the open arms of the elevated plus maze compared with wild-type mice. MOP-KO mice also displayed significantly decreased immobility in a 15 min tail-suspension test compared with wild-type mice. Similarly, MOP-KO mice exhibited significantly decreased immobility on days 2, 3, and 4 in a 6 min forced swim test conducted for 5 consecutive days. The increase in plasma corticosterone concentration induced by tail-suspension, repeated forced swim, or restraint stress was reduced in MOP-KO mice compared with wild-type mice. Corticosterone levels were not different between wild-type and MOP-KO mice before stress exposure. In contrast, although female mice tended to exhibit fewer anxiety-like responses in the tail-suspension test in both genotypes, no significant gender differences were observed in stress-induced emotional responses. These results suggest that MOPs play an important facilitatory role in emotional responses to stress, including anxiety- and depression-like behavior and corticosterone levels. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Ide, Soichiro; Ishihara, Kumatoshi] Hiroshima Int Univ, Neuropharmacol Lab, Fac Pharmaceut Sci, Hirokoshingai, Kure 7370112, Japan. [Ide, Soichiro; Minami, Masabumi] Hokkaido Univ, Dept Pharmacol, Grad Sch Pharmaceut Sci, Sapporo, Hokkaido 0600812, Japan. [Sora, Ichiro] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 9808574, Japan. [Ikeda, Kazutaka] Tokyo Inst Psychiat, Div Psychobiol, Tokyo 1568585, Japan. [Uhl, George R.] NIDA, Baltimore, MD 21224 USA. RP Ishihara, K (reprint author), Hiroshima Int Univ, Neuropharmacol Lab, Fac Pharmaceut Sci, Hirokoshingai, Kure 7370112, Japan. EM ishihara@ps.hirokoku-u.ac.jp RI Ide, Soichiro/D-5472-2012; Minami, Masabumi/A-3883-2012; Ikeda, Kazutaka/I-4694-2013 OI Minami, Masabumi/0000-0002-0144-0679; Ikeda, Kazutaka/0000-0001-8342-0278 FU Intramural NIH HHS [Z01 DA000165-13, Z01 DA000406-10, Z99 DA999999] NR 39 TC 28 Z9 32 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2010 VL 58 IS 1 BP 241 EP 247 DI 10.1016/j.neuropharm.2009.07.005 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 536NS UT WOS:000273051700031 PM 19596019 ER PT J AU Xi, ZX Kiyatkin, M Li, X Peng, XQ Wiggins, A Spiller, K Li, J Gardner, EL AF Xi, Zheng-Xiong Kiyatkin, Michael Li, Xia Peng, Xiao-Qing Wiggins, Armina Spiller, Krista Li, Jie Gardner, Eliot L. TI N-acetylaspartylglutamate (NAAG) inhibits intravenous cocaine self-administration and cocaine-enhanced brain-stimulation reward in rats SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Neuropharmacology Conference CY OCT 14-16, 2009 CL Chicago, IL DE 2-PMPA; NAAG; LY341495; Cocaine; DA; mGlu2; mGlu3; Self-administration; Brain reward ID METABOTROPIC GLUTAMATE-RECEPTOR; LINKED-ACIDIC DIPEPTIDASE; VENTRAL TEGMENTAL AREA; CENTRAL AMYGDALA INJECTIONS; AGONIST LY379268 ATTENUATE; NUCLEUS-ACCUMBENS SHELL; NASAL DRUG-DELIVERY; DOPAMINE RELEASE; INDUCED REINSTATEMENT; ANTIPSYCHOTIC ACTIVITY AB Pharmacological activation of group II metabotropic glutamate (mGlu2 and mGlu3) receptors inhibits reward-seeking behavior and/or rewarding efficacy induced by drugs (cocaine, nicotine) or natural rewards (food, sucrose). In the present study, we investigated whether elevation of brain N-acetylaspartylglutamate (NAAG), an endogenous group II mGlu receptor agonist, by the NAAG peptidase inhibitor 2-PMPA attenuates cocaine's rewarding effects, as assessed by intravenous cocaine self-administration and intracranial electrical brain-stimulation reward (BSR) in rats. Systemic administration of 2-PMPA (10, 30, 100 mg/kg, i.p.) or intranasal administration of NAAG (100, 300 mu g/10 mu l/nostril) significantly inhibited intravenous cocaine self-administration under progressive-ratio (PR), but not under fixed-ratio 2 (FR2), reinforcement conditions. In addition, 2-PMPA (1, 10, 30 mg/kg, i.p) or NAAG (50, 100 mu g/10 mu l/nostril) significantly inhibited cocaine-enhanced BSR, but not basal BSR. Pretreatment with LY341495 (1 mg/kg, i.p.), a selective mGlu2/3 receptor antagonist prevented the inhibitory effects produced by 2-PMPA or NAAG in both the self-administration and BSR paradigms. In vivo microdialysis demonstrated that 2-PMPA (10, 30, 100 mg/kg) dose-dependently attenuated cocaine-enhanced extracellular dopamine (DA) in the nucleus accumbens (NAc). 2-PMPA alone inhibited basal NAc DA release, an effect that was prevented by LY341495. These findings suggest that systemic administration of 2-PMPA or intranasal administration of NAAG inhibits cocaine's rewarding efficacy and cocaine-enhanced NAc DA - likely by activation of presynaptic mGlu2/3 receptors in the NAc. These data suggest a potential utility for 2-PMPA or NAAG in the treatment of cocaine addiction. Published by Elsevier Ltd. C1 [Xi, Zheng-Xiong; Kiyatkin, Michael; Li, Xia; Peng, Xiao-Qing; Wiggins, Armina; Spiller, Krista; Li, Jie; Gardner, Eliot L.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Xi, ZX (reprint author), NIDA, Intramural Res Program, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov OI PENG, XIAOQING/0000-0002-7272-5428 FU Intramural NIH HHS [Z99 DA999999] NR 67 TC 22 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2010 VL 58 IS 1 BP 304 EP 313 DI 10.1016/j.neuropharm.2009.06.016 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 536NS UT WOS:000273051700038 PM 19559037 ER PT S AU Tian, F Marini, AM Lipsky, RH AF Tian, Feng Marini, Ann M. Lipsky, Robert H. BE Andrews, RJ Slikker, W Trembly, B Patterson, TA TI Effects of histone deacetylase inhibitor Trichostatin A on epigenetic changes and transcriptional activation of Bdnf promoter 1 by rat hippocampal neurons SO NEUROPROTECTIVE AGENTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 9th International Conference on Neuroprotective Agents CY SEP 07-11, 2008 CL Marine Biol Lab, Woods Hole, MA HO Marine Biol Lab DE brain-derived neurotrophic factor; chromatin remodeling; epigenetic modification; histone; HDAC; TSA ID C6 GLIOMA-CELLS; NEUROTROPHIC-FACTOR; CHROMATIN REGULATION; GENE-TRANSCRIPTION; VALPROIC ACID; EXPRESSION; PLASTICITY; MOUSE; ACETYLATION; PHOSPHORYLATION AB Histone acetylation/deacetylation is a central mechanism for regulating transcription through chromatin remodeling. The brain-derived neurotrophic factor gene (Bdnf) is regulated in part through chromatin remodeling. An inhibitor of histone deacetylase (HDAC) activity, Trichostatin A (TSA), has differential effects on two activation dependent regions of the Bdnf gene physically linked to transcription sites for exons 1 and 4. We determined that TSA treatment of cultures of hippocampal neurons produced a stronger response at promoter 1. Transcriptional activation of promoter 1 correlated with increased occupancy of the promoter by acetylated histones (H3AcK9/K14). TSA treatment also produced a time-dependent increase in the level of H3AcK9 and H3AcK14 protein and Hdac1 mRNA levels and HDAC1 protein levels. Taken together, these findings suggest that inhibition of HDAC activity by TSA activates Bdnf transcription and a compensatory change in HDAC1 expression in neurons. This response may reflect a genome-wide change in gene expression. C1 [Tian, Feng] NCI, Sect Canc Genet, Genet Branch, NIH, Bethesda, MD 20892 USA. [Marini, Ann M.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. [Marini, Ann M.] Uniformed Serv Univ Hlth Sci, Program Neurosci, Bethesda, MD 20814 USA. [Lipsky, Robert H.] Inova Hlth Syst, Inova Fairfax Hosp, Dept Neurosci, Falls Church, VA USA. RP Lipsky, RH (reprint author), 3300 Gallows Rd, Falls Church, VA 22042 USA. EM robert.lipsky@inova.org OI Lipsky, Robert/0000-0001-7753-1473 FU Defense Brain and Spinal Cord Injury Program [F-192EG-C1] FX This study was supported by an extramural grant F-192EG-C1 from the Defense Brain and Spinal Cord Injury Program (AMM). NR 33 TC 29 Z9 31 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-777-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1199 BP 186 EP 193 DI 10.1111/j.1749-6632.2009.05175.x PG 8 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BRJ59 UT WOS:000282838900021 PM 20633124 ER PT J AU Quiroz, JA Machado-Vieira, R Zarate, CA Manji, HK AF Quiroz, Jorge A. Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. Manji, Husseini K. TI Novel Insights into Lithium's Mechanism of Action: Neurotrophic and Neuroprotective Effects SO NEUROPSYCHOBIOLOGY LA English DT Article DE Neurodegenerative disorders; B-cell lymphoma 2; Protein kinase C; Glycogen synthase kinase 3; Brain-derived neurotrophic factor; Arachidonic acid; Bipolar disorder ID PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE KINASE-3; NERVE GROWTH-FACTOR; BIPOLAR DISORDER PATIENTS; GRAY-MATTER VOLUME; IN-VIVO EVIDENCE; MOOD STABILIZERS; RAT HIPPOCAMPUS; MESSENGER-RNA; ARACHIDONIC-ACID AB The monovalent cation lithium partially exerts its effects by activating neurotrophic and neuroprotective cellular cascades. Here, we discuss the effects of lithium on oxidative stress, programmed cell death (apoptosis), inflammation, glial dysfunction, neurotrophic factor functioning, excito-toxicity, and mitochondrial stability. In particular, we review evidence demonstrating the action of lithium on cyclic adenosine monophosphate (cAMP)-mediated signal transduction, cAMP response element binding activation, increased expression of brain-derived neurotrophic factor, the phosphatidylinositide cascade, protein kinase C inhibition, glycogen synthase kinase 3 inhibition, and B-cell lymphoma 2 expression. Notably, we also review data from clinical studies demonstrating neurotrophic effects of lithium. We expect that a better understanding of the clinically relevant pathophysiological targets of lithium will lead to improved treatments for those who suffer from mood as well as neurodegenerative disorders. Copyright (C) 2010 S. Karger AG, Basel C1 [Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, LLC, Titusville, NJ USA. [Quiroz, Jorge A.] Hoffmann La Roche Inc, Pharma Dev & Exploratory Neurosci, Nutley, NJ 07110 USA. [Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut Mood & Anxiety Disorders Res Progr, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), Johnson & Johnson Pharmaceut Grp, 1125 Trenton Harbourton Rd,E32000, Titusville, NJ USA. EM hmanji@its.jnj.com RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 107 TC 81 Z9 82 U1 0 U2 18 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X EI 1423-0224 J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2010 VL 62 IS 1 BP 50 EP 60 DI 10.1159/000314310 PG 11 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 594ZC UT WOS:000277579200007 PM 20453535 ER PT J AU Schulze, TG Alda, M Adli, M Akula, N Ardau, R Bui, ET Chillotti, C Cichon, S Czerski, P Del Zompo, M Detera-Wadleigh, SD Grof, P Gruber, O Hashimoto, R Hauser, J Hoban, R Iwata, N Kassem, L Kato, T Kittel-Schneider, S Kliwicki, S Kelsoe, JR Kusumi, I Laje, G Leckband, SG Manchia, M MacQueen, G Masui, T Ozaki, N Perlis, RH Pfennig, A Piccardi, P Richardson, S Rouleau, G Reif, A Rybakowski, JK Sasse, J Schumacher, J Severino, G Smoller, JW Squassina, A Turecki, G Young, LT Yoshikawa, T Bauer, M McMahon, FJ AF Schulze, Thomas G. Alda, Martin Adli, Mazda Akula, Nirmala Ardau, Raffaella Bui, Elise T. Chillotti, Caterina Cichon, Sven Czerski, Piotr Del Zompo, Maria Detera-Wadleigh, Sevilla D. Grof, Paul Gruber, Oliver Hashimoto, Ryota Hauser, Joanna Hoban, Rebecca Iwata, Nakao Kassem, Layla Kato, Tadafumi Kittel-Schneider, Sarah Kliwicki, Sebastian Kelsoe, John R. Kusumi, Ichiro Laje, Gonzalo Leckband, Susan G. Manchia, Mirko MacQueen, Glenda Masui, Takuya Ozaki, Norio Perlis, Roy H. Pfennig, Andrea Piccardi, Paola Richardson, Sara Rouleau, Guy Reif, Andreas Rybakowski, Janusz K. Sasse, Johanna Schumacher, Johannes Severino, Giovanni Smoller, Jordan W. Squassina, Alessio Turecki, Gustavo Young, L. Trevor Yoshikawa, Takeo Bauer, Michael McMahon, Francis J. TI The International Consortium on Lithium Genetics (ConLiGen): An Initiative by the NIMH and IGSLI to Study the Genetic Basis of Response to Lithium Treatment SO NEUROPSYCHOBIOLOGY LA English DT Article DE Manic-depressive illness; Schizoaffective disorder; Mood stabilizer; Antidepressants; Suicidal behavior; Genome-wide association study; Neurogenesis; Neuroplasticity ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; BIPOLAR-DISORDER; ANTIDEPRESSANT TREATMENT; SUICIDAL IDEATION; DRUG DISCOVERY; D COHORT; ASSOCIATION; DEPRESSION; PHARMACOGENETICS AB For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic 'fashions', and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health, lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts. Copyright (C) 2010 S. Karger AG, Basel C1 [Schulze, Thomas G.; Akula, Nirmala; Bui, Elise T.; Detera-Wadleigh, Sevilla D.; Kassem, Layla; Laje, Gonzalo; Richardson, Sara; Schumacher, Johannes; McMahon, Francis J.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hoban, Rebecca; Kelsoe, John R.; Leckband, Susan G.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Hoban, Rebecca; Kelsoe, John R.] VA San Diego Healthcare Syst, Dept Psychiat, San Diego, CA USA. [Leckband, Susan G.] VA San Diego Healthcare Syst, Dept Pharm, La Jolla, CA USA. [Leckband, Susan G.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Perlis, Roy H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Perlis, Roy H.; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA USA. [Schulze, Thomas G.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Adli, Mazda] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. [Cichon, Sven; Schumacher, Johannes] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Cichon, Sven; Schumacher, Johannes] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Gruber, Oliver] Univ Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany. [Kittel-Schneider, Sarah; Reif, Andreas] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany. [Pfennig, Andrea; Sasse, Johanna; Bauer, Michael] Tech Univ Dresden, Dept Psychiat & Psychotherapy, Univ Hosp Carl Gustav Carus, Dresden, Germany. [Alda, Martin] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. [Grof, Paul] Mood Disorders Ctr Ottawa, Ottawa, ON, Canada. [Grof, Paul] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [MacQueen, Glenda] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Rouleau, Guy] Univ Montreal, CHU St Justine Res Ctr, Dept Med, Montreal, PQ H3C 3J7, Canada. [Turecki, Gustavo] McGill Univ, Dept Psychiat, Douglas Hosp, Res Inst, Montreal, PQ, Canada. [Young, L. Trevor] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Del Zompo, Maria; Manchia, Mirko; Piccardi, Paola; Severino, Giovanni; Squassina, Alessio] Univ Cagliari, BB Brodie Dept Neurosci, Cagliari, Italy. [Czerski, Piotr; Hauser, Joanna] Karol Marcinkowski Univ Med Sci, Psychiat Genet Unit, Poznan, Poland. [Kliwicki, Sebastian; Rybakowski, Janusz K.] Karol Marcinkowski Univ Med Sci, Dept Adult Psychiat, Poznan, Poland. [Hashimoto, Ryota] Osaka Univ, Grad Sch Med, Osaka, Japan. [Iwata, Nakao] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. [Kato, Tadafumi] RIKEN, Brain Sci Inst, Lab Mol Dynam Mental Disorders, Saitama, Japan. [Yoshikawa, Takeo] RIKEN, Brain Sci Inst, Lab Mol Psychiat, Saitama, Japan. [Kusumi, Ichiro; Masui, Takuya] Hokkaido Univ, Dept Psychiat, Grad Sch Med, Sapporo, Hokkaido, Japan. [Ozaki, Norio] Nagoya Univ, Dept Psychiat, Grad Sch Med, Nagoya, Aichi 4648601, Japan. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. RP Schulze, TG (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Dept Hlth & Human Serv, 35 Convent Dr,Bldg 35,Rm 1A205,MSC 3719, Bethesda, MD 20892 USA. EM schulzet@mail.nih.gov RI Czerski, Piotr/B-8446-2011; Kusumi, Ichiro/A-4067-2012; Laje, Gonzalo/L-2654-2014; Hashimoto, Ryota/P-8572-2014; Ozaki, Norio/M-8908-2014; Schumacher, Johannes/F-4970-2015; Severino, Giovanni/B-2823-2012; Manchia, Mirko/E-8751-2010; Alda, Martin/F-5812-2010; Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Kato, Tadafumi/J-3583-2014; OI Czerski, Piotr/0000-0003-0745-5916; Laje, Gonzalo/0000-0003-2763-3329; Hashimoto, Ryota/0000-0002-5941-4238; Ozaki, Norio/0000-0002-7360-4898; Schumacher, Johannes/0000-0001-9217-6457; Alda, Martin/0000-0001-9544-3944; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Kato, Tadafumi/0000-0001-7856-3952; Manchia, Mirko/0000-0003-4175-6413; Kittel-Schneider, Sarah/0000-0003-3057-6150; McMahon, Francis/0000-0002-9469-305X; Squassina, Alessio/0000-0001-7415-7607 FU NIMH [MH079799]; NARSAD; Canadian Institutes of Health Research (CIHR) [64410]; Deutsche Forschungsgemeinschaft (DFG) [KFO 125, SFB TRR 58]; German Ministry for Education and Research (BMBF) [IZKF N-4]; Regional Councillorship of Health FX This research was in part supported by the Intramural Program of the NIMH. Dr. Thomas G. Schulze's work is furthermore supported by NARSAD. Dr. Martin Alda's work on the phenotype of lithium response has been supported by grants from the Canadian Institutes of Health Research (CIHR, grant 64410) and by NARSAD. Dr. Smoller's work is supported in part by a grant from the NIMH (MH079799). Dr. Reif is supported by the Deutsche Forschungsgemeinschaft (DFG) (KFO 125 and SFB TRR 58) and the German Ministry for Education and Research (BMBF) (IZKF N-4). The work of the Cagliari group was partly supported by the Regional Councillorship of Health, 'Regione Autonoma della Sardegna'. NR 28 TC 43 Z9 43 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2010 VL 62 IS 1 BP 72 EP 78 DI 10.1159/000314708 PG 7 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 594ZC UT WOS:000277579200009 PM 20453537 ER PT J AU Walenski, M Weickert, TW Maloof, CJ Ullman, MT AF Walenski, Matthew Weickert, Thomas W. Maloof, Christopher J. Ullman, Michael T. TI Grammatical processing in schizophrenia: Evidence from morphology SO NEUROPSYCHOLOGIA LA English DT Article DE Inflection; Prefrontal cortex; Temporal lobe; Striatum; Thought disorder ID FORMAL THOUGHT-DISORDER; PAST-TENSE MORPHOLOGY; DECLARATIVE/PROCEDURAL MODEL; LANGUAGE; SYSTEM; FLUENCY; MEMORY; IMPAIRMENTS; FREQUENCY; CAPACITY AB Patients with psychiatric disorders such as schizophrenia commonly present with impaired language. Here we investigate language in schizophrenia with a focus on inflectional morphology, using an intensively studied and relatively well-understood linguistic paradigm. Patients with schizophrenia (n = 43) and age-matched healthy control subjects (n = 42) were asked to produce past tenses of regular (slip), irregular (swim), and novel (plag) English verbs. Patients were impaired at regulars and novels (slipped, plagged), with relative sparing of irregulars (swam), controlling for numerous subject- and item-specific factors (e.g., IQ, phonological complexity). Additionally, patients' thought-disorder scores significantly predicted their performance at regular and novel (but not irregular) past-tense production. The results support grammatical deficits in schizophrenia, with a relative sparing of lexical memory, and suggest that thought disorder may be linked with grammatical impairments in the disorder. Published by Elsevier Ltd. C1 [Walenski, Matthew] Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. [Weickert, Thomas W.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Weickert, Thomas W.] Univ New S Wales, Sch Psychiat, Sydney, NSW 2031, Australia. [Weickert, Thomas W.] Prince Wales Med Res Inst, Sydney, NSW 2031, Australia. [Maloof, Christopher J.; Ullman, Michael T.] Georgetown Univ, Dept Neurosci, Washington, DC 20007 USA. RP Walenski, M (reprint author), Univ Calif San Diego, Dept Psychol, 9500 Gilman Dr,MC 0109, La Jolla, CA 92093 USA. EM mwalenski@ucsd.edu; t.weickert@unsw.edu.au; michael@georgetown.edu FU National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services; National Science Foundation [SBR-9905273]; National Institutes of Health [MH58189, HD049347] FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services and additional support to MTU from the National Science Foundation (grant number SBR-9905273) and the National Institutes of Health (R01 grant numbers MH58189 and HD049347). NR 64 TC 6 Z9 6 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 2010 VL 48 IS 1 BP 262 EP 269 DI 10.1016/j.neuropsychologia.2009.09.012 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 550NU UT WOS:000274135500030 PM 19766129 ER PT J AU Wolf, RC Sambataro, F Lohr, C Steinbrink, C Martin, C Vasic, N AF Wolf, Robert Christian Sambataro, Fabio Lohr, Christina Steinbrink, Claudia Martin, Claudia Vasic, Nenad TI Functional brain network abnormalities during verbal working memory performance in adolescents and young adults with dyslexia SO NEUROPSYCHOLOGIA LA English DT Article DE Dyslexia; Functional magnetic resonance imaging; Independent component analysis; Functional connectivity; Prefrontal cortex; Temporal cortex ID MEDIAL TEMPORAL-LOBE; DEVELOPMENTAL DYSLEXIA; READING-DISABILITY; EXECUTIVE FUNCTIONS; FRONTOPOLAR CORTEX; INHIBITORY CONTROL; PREFRONTAL CORTEX; TERM-MEMORY; CHILDREN; CONNECTIVITY AB Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional neuroanatomy underlying cognitive dysfunction in dyslexia. In this study, functional magnetic resonance imaging and multivariate analytic techniques were used to investigate patterns of functional connectivity during a verbal WM task in individuals with dyslexia (n = 12) and control subjects (n = 13). Dyslexics were not significantly slower than controls; however, they were less accurate with increasing WM demand. Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included functional networks which were positively correlated with the delay period of the activation task in both healthy controls and dyslexics. Connectivity abnormalities in dyslexics were detected within both networks of interest: within a "phonological" left-lateralized prefrontal network, increased functional connectivity was found in left prefrontal and inferior parietal regions. Within an "executive" bilateral frontoparietal network, dyslexics showed a decreased connectivity pattern comprising bilateral dorsolateral prefrontal and posterior parietal regions, while increased connectivity was found in the left angular gyrus, the left hippocampal cortex and the right thalamus. The functional connectivity strength in the latter regions was associated with WM task accuracy and with the numbers of errors during a spelling test. These data suggest functional connectivity abnormalities in two spatiotemporally dissociable brain networks underlying WM dysfunction in individuals with dyslexia. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Wolf, Robert Christian; Vasic, Nenad] Univ Ulm, Dept Psychiat & Psychotherapy 3, D-89075 Ulm, Germany. [Sambataro, Fabio] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Lohr, Christina; Steinbrink, Claudia] Univ Ulm, Transfer Ctr Neurosci & Learning, D-89075 Ulm, Germany. [Steinbrink, Claudia] Univ Kaiserslautern, Dept Psychol 2, Fac Social Sci, D-67663 Kaiserslautern, Germany. [Martin, Claudia] Univ Wurzburg, Dept Psychol 4, D-97070 Wurzburg, Germany. RP Wolf, RC (reprint author), Univ Ulm, Dept Psychiat & Psychotherapy 3, Leimgrubenweg 12-14, D-89075 Ulm, Germany. EM christian.wolf@uni-ulm.de RI Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X NR 77 TC 18 Z9 19 U1 1 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 2010 VL 48 IS 1 BP 309 EP 318 DI 10.1016/j.neuropsychologia.2009.09.020 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 550NU UT WOS:000274135500035 PM 19782695 ER PT J AU Lacey, EH Lott, SN Snider, SF Sperling, A Friedman, RB AF Lacey, E. H. Lott, S. N. Snider, S. F. Sperling, A. Friedman, R. B. TI Multiple Oral Re-reading treatment for alexia: The parts may be greater than the whole SO NEUROPSYCHOLOGICAL REHABILITATION LA English DT Article DE Alexia; Aphasia; Reading; Treatment ID PURE ALEXIA; REHABILITATION AB This study examines the reasons for the success of Multiple Oral Re-reading (MOR; Moyer, 1979), a non-invasive, easily administered alexia treatment that has been reported in the literature and is currently in clinical use. The treatment consists of reading text passages aloud multiple times a day. Findings that MOR improves reading speed on practised as well as novel text have been inconsistent, making MOR's role in the rehabilitation of alexia unclear. We hypothesised that MOR's treatment mechanism works through repetition of high frequency words (i.e., bottom-up processing). We designed and controlled our text passages to test the hypothesis that participants would not improve on all novel text but would improve on text that includes a critical mass of the words contained in the passages they were re-reading. We further hypothesised that the improvement would be at the level of their specific alexic deficit. We tested four participants with phonological alexia and two with pure alexia during 8 weeks of MOR treatment. Contrary to the conclusions of previous studies, our results indicate that improvements in top-down processing cannot explain generalisation in MOR and that much of the improvement in reading is through repetition of the practised words. However, most patients also showed improvement when specific phrases were re-used in novel passages, indicating that practice of difficult words in context may be crucial to reading improvement. C1 [Lacey, E. H.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. [Sperling, A.] NIMH, Bethesda, MD 20892 USA. RP Lacey, EH (reprint author), Georgetown Univ, Med Ctr, Dept Neurol, Bldg D,Suite 207E,4000 Reservoir Rd NW, Washington, DC 20057 USA. EM EHL4@georgetown.edu FU NIH [R01 HD036019] FX This study was supported by NIH grant R01 HD036019. We would like to thank the many people involved in making this project a reality: Robyn Oliver, Laurie Glezer, Kim Wittenberg, Leah Orchinik, Elizabeth Christy, and Sean Rogers. NR 19 TC 11 Z9 11 U1 2 U2 18 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0960-2011 J9 NEUROPSYCHOL REHABIL JI Neuropsychol. Rehabil. PY 2010 VL 20 IS 4 BP 601 EP 623 AR PII 923303443 DI 10.1080/09602011003710993 PG 23 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 622BT UT WOS:000279634300007 PM 20574915 ER PT J AU Davis, M Walker, DL Miles, L Grillon, C AF Davis, Michael Walker, David L. Miles, Leigh Grillon, Christian TI Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE amygdala; bed nucleus stria terminalis; startle; CRF; SSRIs; context conditioning ID CORTICOTROPIN-RELEASING-FACTOR; POSTTRAUMATIC-STRESS-DISORDER; ACOUSTIC STARTLE RESPONSE; GENE-RELATED PEPTIDE; HORMONE MESSENGER-RNA; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; COMMON MENTAL-DISORDERS; LIGHT-ENHANCED STARTLE; BASE-LINE STARTLE; SEROTONIN REUPTAKE INHIBITORS AB Data will be reviewed using the acoustic startle reflex in rats and humans based on our attempts to operationally define fear vs anxiety. Although the symptoms of fear and anxiety are very similar, they also differ. Fear is a generally adaptive state of apprehension that begins rapidly and dissipates quickly once the threat is removed (phasic fear). Anxiety is elicited by less specific and less predictable threats, or by those that are physically or psychologically more distant. Thus, anxiety is a more long-lasting state of apprehension (sustained fear). Rodent studies suggest that phasic fear is mediated by the amygdala, which sends outputs to the hypothalamus and brainstem to produce symptoms of fear. Sustained fear is also mediated by the amygdala, which releases corticotropin-releasing factor, a stress hormone that acts on receptors in the bed nucleus of the stria terminalis (BNST), a part of the so-called 'extended amygdala.' The amygdala and BNST send outputs to the same hypothalamic and brainstem targets to produce phasic and sustained fear, respectively. In rats, sustained fear is more sensitive to anxiolytic drugs. In humans, symptoms of clinical anxiety are better detected in sustained rather than phasic fear paradigms. Neuropsychopharmacology Reviews (2010) 35, 105-135; doi:10.1038/npp.2009.109; published online 19 August 2009 C1 [Davis, Michael; Walker, David L.; Miles, Leigh] Emory Univ, Yerkes Natl Primate Ctr, Dept Psychiat, Atlanta, GA 30329 USA. [Davis, Michael; Walker, David L.; Miles, Leigh] Ctr Behav Neurosci, Atlanta, GA USA. [Grillon, Christian] NIMH, Unit Affect Psychophysiol, Mood & Anxiety Disorder Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. RP Davis, M (reprint author), Emory Univ, Yerkes Natl Primate Ctr, Dept Psychiat, 954 Gatewood Dr NE Room 5200, Atlanta, GA 30329 USA. EM mdavis4@emory.edu FU NIMH [MH069056, MH47840, MH57250, MH59906, 1U19 MH069056]; Science and Technology Center [IBN-9876754]; NARSAD Young Investigator award; American Psychological Association Diversity Program in Neuroscience [5T32 MH18882]; Intramural Research Program at NIMH FX This research was supported by NIMH Grants MH069056, MH47840, MH57250, and MH59906 (MD), the Science and Technology Center (The Center for Behavioral Neuroscience of the National Science Foundation under Agreement No. IBN-9876754), a NARSAD Young Investigator award (DLW), The American Psychological Association Diversity Program in Neuroscience Predoctoral Fellowship 5T32 MH18882 (LM), and the Intramural Research Program at NIMH (CG). Principles of Laboratory Animal Care (NIH publication no. 86-23, revised 1985) was followed and all procedures were approved by the Emory IACUC and the NIH IRB. The CRF1 antagonist was supplied by GlaxoSmithKline (GSK) as part of the NIMH Grant 1U19 MH069056 funded by the NIMH. GSK did not fund any of this research. The authors thank Ioline Henter for her outstanding editorial assistance. NR 317 TC 437 Z9 442 U1 21 U2 79 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2010 VL 35 IS 1 BP 105 EP 135 DI 10.1038/npp.2009.109 PG 31 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 532XV UT WOS:000272784600007 PM 19693004 ER PT J AU Price, JL Drevets, WC AF Price, Joseph L. Drevets, Wayne C. TI Neurocircuitry of Mood Disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE limbic system; amygdala; medial prefrontal cortex; major depressive disorder; neuroimaging; bipolar disorder ID MEDIAL PREFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; ANTERIOR CINGULATE CORTEX; MEDIODORSAL THALAMIC NUCLEUS; TREATMENT-RESISTANT DEPRESSION; REGIONAL CEREBRAL METABOLISM; VAGUS NERVE-STIMULATION; DEEP BRAIN-STIMULATION; POSTERIOR PARAVENTRICULAR THALAMUS; MAGNETIC-RESONANCE SPECTROSCOPY AB This review begins with a brief historical overview of attempts in the first half of the 20th century to discern brain systems that underlie emotion and emotional behavior. These early studies identified the amygdala, hippocampus, and other parts of what was termed the 'limbic' system as central parts of the emotional brain. Detailed connectional data on this system began to be obtained in the 1970s and 1980s, as more effective neuroanatomical techniques based on axonal transport became available. In the last 15 years these methods have been applied extensively to the limbic system and prefrontal cortex of monkeys, and much more specific circuits have been defined. In particular, a system has been described that links the medial prefrontal cortex and a few related cortical areas to the amygdala, the ventral striatum and pallidum, the medial thalamus, the hypothalamus, and the periaqueductal gray and other parts of the brainstem. A large body of human data from functional and structural imaging, as well as analysis of lesions and histological material indicates that this system is centrally involved in mood disorders. Neuropsychopharmacology Reviews (2010) 35, 192-216; doi:10.1038/npp.2009.104; published online 19 August 2009 C1 [Price, Joseph L.] Washington Uninvers, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. RP Price, JL (reprint author), Washington Uninvers, Sch Med, Dept Anat & Neurobiol, 660 S Euclid Ave,Campus Box 8108, St Louis, MO 63110 USA. EM pricej@wustl.edu FU USPHS/NIMH [R01 MH070941] FX JLP was supported by Grant R01 MH070941 from the USPHS/NIMH. NR 273 TC 551 Z9 565 U1 30 U2 152 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2010 VL 35 IS 1 BP 192 EP 216 DI 10.1038/npp.2009.104 PG 25 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 532XV UT WOS:000272784600011 PM 19693001 ER PT J AU Koob, GF Volkow, ND AF Koob, George F. Volkow, Nora D. TI Neurocircuitry of Addiction SO NEUROPSYCHOPHARMACOLOGY LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; COCAINE-SEEKING BEHAVIOR; DOPAMINE TRANSPORTER OCCUPANCY; PSYCHOMOTOR STIMULANT-DRUGS; RECEPTOR SURFACE EXPRESSION; VENTRAL TEGMENTAL AREA; ANXIETY-LIKE BEHAVIOR; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; OPIATE WITHDRAWAL AB Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages: 'binge/intoxication', 'withdrawal/negative affect', and 'preoccupation/anticipation' (craving). Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex-dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction. Neuropsychopharmacology Reviews (2010) 35, 217-238; doi:10.1038/npp.2009.110; published online 26 August 2009 C1 [Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA. RP Koob, GF (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, 10550 N Torrey Pines Rd,SP30-2400, La Jolla, CA 92037 USA. EM gkoob@scripps.edu RI koob, george/P-8791-2016 FU Pearson Center for Alcoholism and Addiction Research; National Institutes of Health; National Institute on Alcohol Abuse and Alcoholism [AA12602, AA08459, AA06420]; National Institute on Drug Abuse [DA04043, DA04398, DA10072]; National Institute of Diabetes and Digestive and Kidney Diseases [DK26741]; Tobacco-Related Disease Research Program from the State of California [17RT-0095] FX This is publication number 20084 from The Scripps Research Institute. Preparation of this work was supported by the Pearson Center for Alcoholism and Addiction Research and National Institutes of Health grants AA12602, AA08459, and AA06420 from the National Institute on Alcohol Abuse and Alcoholism; DA04043, DA04398, and DA10072 from the National Institute on Drug Abuse; DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases; and 17RT-0095 from the Tobacco-Related Disease Research Program from the State of California. We thank Michael Arends and Ruben Baler for their assistance with paper preparation. NR 239 TC 1464 Z9 1496 U1 67 U2 473 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2010 VL 35 IS 1 BP 217 EP 238 DI 10.1038/npp.2009.110 PG 22 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 532XV UT WOS:000272784600012 PM 19710631 ER PT J AU Eisenberg, DP Berman, KF AF Eisenberg, Daniel Paul Berman, Karen Faith TI Executive Function, Neural Circuitry, and Genetic Mechanisms in Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE schizophrenia; cognition; executive function; working memory; neuroimaging; genetics ID CEREBRAL-BLOOD-FLOW; ANTERIOR CINGULATE CORTEX; DORSOLATERAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; CATECHOL-O-METHYLTRANSFERASE; SPATIAL WORKING-MEMORY; MESSENGER-RNA EXPRESSION; EVENT-RELATED FMRI; MAGNETIC-RESONANCE SPECTROSCOPY; 1ST EPISODE SCHIZOPHRENIA AB After decades of research aimed at elucidating the pathophysiology and etiology of schizophrenia, it has become increasingly apparent that it is an illness knowing few boundaries. Psychopathological manifestations extend across several domains, impacting multiple facets of real-world functioning for the affected individual. Even within one such domain, arguably the most enduring, difficult to treat, and devastating to long-term functioning-executive impairment-there are not only a host of disrupted component processes, but also a complex underlying dysfunctional neural architecture. Further, just as implicated brain structures (eg, dorsolateral prefrontal cortex) through postmortem and neuroimaging techniques continue to show alterations in multiple, interacting signaling pathways, so too does evolving understanding of genetic risk factors suggest multiple molecular entry points to illness liability. With this expansive network of interactions in mind, the present chapter takes a systems-level approach to executive dysfunction in schizophrenia, by identifying key regions both within and outside of the frontal lobes that show changes in schizophrenia and are important in cognitive control neural circuitry, summarizing current knowledge of their relevant functional interactions, and reviewing emerging links between schizophrenia risk genetics and characteristic executive circuit aberrancies observed with neuroimaging methods. Neuropsychopharmacology Reviews (2010) 35, 258-277; doi:10.1038/npp.2009.111; published online 19 August 2009 C1 [Eisenberg, Daniel Paul; Berman, Karen Faith] NIMH, Sect Integrat Neuroimaging, NIH, DHHS, Bethesda, MD 20892 USA. [Eisenberg, Daniel Paul; Berman, Karen Faith] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,DHHS, Bethesda, MD 20892 USA. RP Berman, KF (reprint author), NIMH, Sect Integrat Neuroimaging, NIH, DHHS, 9000 Rockville Pike,Bldg 10,Room 3C209, Bethesda, MD 20892 USA. EM karen.berman@nih.gov RI Eisenberg, Daniel/S-4342-2016; Eisenberg, Daniel/C-7432-2014 FU National Institute of Mental Health Intramural Research Program FX This work was supported by the National Institute of Mental Health Intramural Research Program. NR 336 TC 104 Z9 104 U1 9 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2010 VL 35 IS 1 BP 258 EP 277 DI 10.1038/npp.2009.111 PG 20 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 532XV UT WOS:000272784600014 PM 19693005 ER PT J AU Besson, M Belin, D McNamara, R Theobald, DEH Castel, A Beckett, VL Crittenden, BM Newman, AH Everitt, BJ Robbins, TW Dalley, JW AF Besson, Morgane Belin, David McNamara, Ruth Theobald, David E. H. Castel, Aude Beckett, Victoria L. Crittenden, Ben M. Newman, Amy H. Everitt, Barry J. Robbins, Trevor W. Dalley, Jeffrey W. TI Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE impulsivity; 5-CSRT task; NAcbs; DA receptors; nafadotride; aripiprazole ID REACTION-TIME-TASK; COCAINE-SEEKING BEHAVIOR; D-3 RECEPTOR; NEUROBEHAVIORAL MECHANISMS; INHIBITORY CONTROL; IN-VIVO; LESIONS; PERFORMANCE; MODULATION; STRIATUM AB Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intra-NAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction. Neuropsychopharmacology (2010) 35, 560-569; doi: 10.1038/npp.2009.162; published online 21 October 2009 C1 [Besson, Morgane; Belin, David; McNamara, Ruth; Theobald, David E. H.; Castel, Aude; Beckett, Victoria L.; Crittenden, Ben M.; Everitt, Barry J.; Robbins, Trevor W.; Dalley, Jeffrey W.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Besson, Morgane; Belin, David; McNamara, Ruth; Theobald, David E. H.; Castel, Aude; Beckett, Victoria L.; Crittenden, Ben M.; Everitt, Barry J.; Robbins, Trevor W.; Dalley, Jeffrey W.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. [Newman, Amy H.] NIDA, Med Chem Sect, IRP, NIH, Baltimore, MD USA. [Dalley, Jeffrey W.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 3EB, England. RP Dalley, JW (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB2 3EB, England. EM jwd20@cam.ac.uk OI Everitt, Barry/0000-0003-4431-6536; Parker, Victoria/0000-0002-8748-4583; belin, david/0000-0002-7383-372X FU Wellcome Trust [076274/2/04/2]; MRC [G0600196, G0401068]; European Communities Sixth Framework Programme [LSHM-CT-2007037286]; National Institute on Drug Abuse; 'Fondation pour la Recherche Medicale' fellowship FX This study was funded by the Wellcome Trust (076274/2/04/2), MRC (G0600196, G0401068), IMAGEN under the European Communities Sixth Framework Programme (LSHM-CT-2007037286), and the National Institute on Drug Abuse (Intramural Research Program). MB was supported by a 'Fondation pour la Recherche Medicale' fellowship. The authors thank Alan G Lyon for technical assistance. NR 53 TC 58 Z9 59 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2010 VL 35 IS 2 BP 560 EP 569 DI 10.1038/npp.2009.162 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 532NZ UT WOS:000272757800019 PM 19847161 ER PT J AU Cohen, L AF Cohen, Leonardo TI How studies of motor learning and effects of brain stimulation in animal and human models may contribute to more effective neurorehabilitative strategies SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Cohen, Leonardo] NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2010 VL 68 SU 1 BP E10 EP E10 DI 10.1016/j.neures.2010.07.277 PG 1 WC Neurosciences SC Neurosciences & Neurology GA V24XS UT WOS:000208443700041 ER PT J AU Hori, Y Richmond, B Minamimoto, T AF Hori, Yukiko Richmond, Barry Minamimoto, Takafumi TI Neural coding of predicted and experienced outcome value with temporal discounting in the primate caudate nucleus SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Hori, Yukiko; Minamimoto, Takafumi] Natl Inst Radiol Sci, Mol Imaging Ctr, Chiba 260, Japan. [Minamimoto, Takafumi] NIMH, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2010 VL 68 SU 1 BP E295 EP E295 DI 10.1016/j.neures.2010.07.1310 PG 1 WC Neurosciences SC Neurosciences & Neurology GA V24XS UT WOS:000208443702076 ER PT J AU Jhou, TC AF Jhou, Thomas C. TI Convergence of aversive pathways and function onto the rostromedial tegmental nucleus (RMTg) a major target of habenular efferents SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Jhou, Thomas C.] Natl Inst Drug Abuse, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2010 VL 68 SU 1 BP E16 EP E16 DI 10.1016/j.neures.2010.07.307 PG 1 WC Neurosciences SC Neurosciences & Neurology GA V24XS UT WOS:000208443700071 ER PT J AU Kosaki, H Mishkin, M AF Kosaki, Hiroko Mishkin, Mortimer TI Cytochrome Oxidase distribution in monkey brain agreed with mitochondrial diseases SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Kosaki, Hiroko] Tokyo Hosp, Natl Printing Bur, Tokyo, Japan. [Mishkin, Mortimer] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2010 VL 68 SU 1 BP E198 EP E198 DI 10.1016/j.neures.2010.07.2448 PG 1 WC Neurosciences SC Neurosciences & Neurology GA V24XS UT WOS:000208443701262 ER PT J AU Matsumoto, N Saunders, RC Gothard, KM Richmond, BJ AF Matsumoto, Narihisa Saunders, Richard C. Gothard, Katalin M. Richmond, Barry J. TI Intact perceptual categorization and generalization following removal of inferior temporal area TE in rhesus monkeys SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Matsumoto, Narihisa] AIST, Human Tech Res Inst, Tsukuba, Ibaraki, Japan. [Matsumoto, Narihisa; Saunders, Richard C.; Richmond, Barry J.] NIMH, NIH, Bethesda, MD 20892 USA. [Gothard, Katalin M.] Univ Arizona, Dept Physiol, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2010 VL 68 SU 1 BP E268 EP E269 DI 10.1016/j.neures.2010.07.1194 PG 2 WC Neurosciences SC Neurosciences & Neurology GA V24XS UT WOS:000208443701578 ER PT J AU Roche, K AF Roche, Katherine TI Regulation of NMDA receptor trafficking SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Roche, Katherine] NINDS, Receptor Biol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2010 VL 68 SU 1 BP E9 EP E10 DI 10.1016/j.neures.2010.07.272 PG 2 WC Neurosciences SC Neurosciences & Neurology GA V24XS UT WOS:000208443700036 ER PT J AU Sheng, ZH AF Sheng, Zu-Hang TI Axonal mitochondrial transport and remodeling of synaptic transmission SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Sheng, Zu-Hang] NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2010 VL 68 SU 1 BP E20 EP E20 DI 10.1016/j.neures.2010.07.324 PG 1 WC Neurosciences SC Neurosciences & Neurology GA V24XS UT WOS:000208443700088 ER PT J AU Suzuki, N Fukushi, M Kosaki, K Doyle, A Arikawa-Hirasawa, E Yamada, Y AF Suzuki, Nobuharu Fukushi, Masaya Kosaki, Keisuke Doyle, Andrew Arikawa-Hirasawa, Eri Yamada, Yoshihiko TI Teneurin-4 Is Required for Differentiation and Survival of Oligodendrocytes and Myelination in the CNS SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 [Suzuki, Nobuharu; Fukushi, Masaya; Kosaki, Keisuke; Doyle, Andrew; Yamada, Yoshihiko] NIDCR, NIH, Bethesda, MD 20892 USA. [Arikawa-Hirasawa, Eri] Juntendo Univ, Fac Med, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2010 VL 68 SU 1 BP E57 EP E57 DI 10.1016/j.neures.2010.07.019 PG 1 WC Neurosciences SC Neurosciences & Neurology GA V24XS UT WOS:000208443700255 ER PT J AU Cao, Y Chen, AM Jones, RL Radcliffe, J Caldwell, KL Dietrich, KN Rogan, WJ AF Cao, Yang Chen, Aimin Jones, Robert L. Radcliffe, Jerilynn Caldwell, Kathleen L. Dietrich, Kim N. Rogan, Walter J. TI Does background postnatal methyl mercury exposure in toddlers affect cognition and behavior? SO NEUROTOXICOLOGY LA English DT Article DE Methylmercury; Lead; Children; Neuropsychological tests; Postnatal exposure ID SEYCHELLES CHILD-DEVELOPMENT; METHYLMERCURY EXPOSURE; FETAL METHYLMERCURY; PRENATAL EXPOSURE; BLOOD; AGE; COHORT; ENVIRONMENT; HEALTH; AUTISM AB Because the toxicological effects of mercury (Hg) are more serious in the developing central nervous system of children than adults, there are growing concerns about prenatal and early childhood Hg exposure. This study examined postnatal methylmercury (MeHg) exposure and cognition and behavior in 780 children enrolled in the Treatment of Lead (Pb)-exposed Children clinical trial (TLC) with 396 children allocated to the succimer and 384 to the placebo groups. Mercury exposure was determined from analyses of blood drawn I week before randomization and 1 week after treatment began when succimer had its maximal effect on blood Pb (PbB). The baseline MeHg concentrations were 0.54 mu g/L and 0.52 mu g/L and post-treatment concentrations were 0.51 mu g/L and 0.48 mu g/L for placebo and succimer groups, respectively. Because the baseline characteristics in the two groups were balanced and because succimer had little effect on MeHg concentration and no effect on the cognitive or behavioral test scores, the groups were combined in the analysis of MeHg and neurodevelopment. The children's IQ and neurobehavioral performance were tested at age 2, 5 and 7 years. We saw weak, non-significant but consistently positive associations between blood MeHg and IQ test scores in stratified, spline regression and generalized linear model data analyses. The behavioral problem scores were constant or decreased slightly with increasing MeHg concentration. Additional adjustment for PbB levels in multivariable models did not alter the conclusion for MeHg and IQ scores, but did confirm that concurrent PbB was strongly associated with IQ and behavior in TLC children. The effects of MeHg on neurodevelopmental indices did not substantially differ by PbB strata. We conclude that at the present background postnatal MeHg exposure levels of US children, adverse effects on children's IQ and behavior are not detectable. (C) 2009 Elsevier Inc. All rights reserved. C1 [Dietrich, Kim N.] Univ Cincinnati, Dept Environm Hlth, Div Epidemiol & Biostat, Coll Med, Cincinnati, OH 45267 USA. [Cao, Yang; Rogan, Walter J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Chen, Aimin] Creighton Univ, Dept Prevent Med & Publ Hlth, Sch Med, Omaha, NE 68178 USA. [Jones, Robert L.; Caldwell, Kathleen L.] Ctr Dis Control & Prevent, Organ Analyt Toxicol Branch, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. [Radcliffe, Jerilynn] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Radcliffe, Jerilynn] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Dietrich, KN (reprint author), Univ Cincinnati, Dept Environm Hlth, Div Epidemiol & Biostat, Coll Med, 3223 Eden Ave, Cincinnati, OH 45267 USA. EM kim.dietrich@uc.edu RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 39 TC 14 Z9 14 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JAN PY 2010 VL 31 IS 1 BP 1 EP 9 DI 10.1016/j.neuro.2009.10.017 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 556SE UT WOS:000274611000001 PM 19969021 ER PT J AU Boyd, WA Smith, MV Kissling, GE Freedman, JH AF Boyd, Windy A. Smith, Marjolein V. Kissling, Grace E. Freedman, Jonathan H. TI Medium- and high-throughput screening of neurotoxicants using C. elegans SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE C. elegans; Neurotoxicology; High-throughput screening; Toxicant ID NEMATODE CAENORHABDITIS-ELEGANS; END-POINTS; BEHAVIOR; TOXICITY; SYSTEM; PHARYNX; DEGENERATION; REPRODUCTION; EXPRESSION; SEROTONIN AB The U.S. National Toxicology Program, the U.S. Environmental Protection Agency, and other national and international agencies are committing significant resources towards the development of alternative species to be used as replacements for mammalian models in toxicological studies. Caenorhabditis elegans is a well-characterized soil nematode that is becoming a useful model in the assessment of neurotoxicants. To determine the effects of potential neurotoxicants on C elegans, four medium-throughput (feeding, growth, reproduction and locomotion) and two high-throughput (growth and reproduction) assays have been developed. Three of these assays use the COPAS Biosort, a flow cytometer capable of rapidly measuring thousands of nematodes in minutes. Medium-through put feeding, growth, and reproduction assays were used to assess the toxicity of eight suspected neurotoxicants. For several of the neurotoxicants examined, significant effects were observed at similar concentrations between assays. High-throughput reproduction and growth assays were used to estimate the toxicity of thousands of chemicals in two libraries. These assays will prove useful in evaluating the role of alternative toxicological models in tiered toxicity testing of thousands of chemicals. Published by Elsevier Inc. C1 [Kissling, Grace E.; Freedman, Jonathan H.] NIEHS, Mol Toxicol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Boyd, Windy A.; Freedman, Jonathan H.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Smith, Marjolein V.] SRA Int, Res Triangle Pk, NC 27709 USA. RP Freedman, JH (reprint author), NIEHS, Mol Toxicol Lab, NIH, DHHS, Mail Drop E1-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM freedma1@niehs.nih.gov OI Boyd, Windy/0000-0003-3803-3716 FU NIH, National Institute of Environmental Health Sciences and the National Toxicology Program FX This work was supported, in part, by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences and the National Toxicology Program. NR 69 TC 40 Z9 41 U1 2 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2010 VL 32 IS 1 SI SI BP 68 EP 73 DI 10.1016/j.ntt.2008.12.004 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 560DF UT WOS:000274881500009 PM 19166924 ER PT J AU Hanno, P Lin, A Nordling, J Nyberg, L van Ophoven, A Ueda, T Wein, A AF Hanno, Philip Lin, Alex Nordling, Joergen Nyberg, Leroy van Ophoven, Arndt Ueda, Tomohiro Wein, Alan TI Bladder Pain Syndrome International Consultation on Incontinence SO NEUROUROLOGY AND URODYNAMICS LA English DT Review DE bladder pain; ICUD ID INTERSTITIAL CYSTITIS SYMPTOMS; UNEXPLAINED CLINICAL CONDITIONS; MANAGED CARE POPULATION; SYNDROME/INTERSTITIAL CYSTITIS; CYSTOSCOPIC FINDINGS; DIAGNOSTIC-CRITERIA; CONTINENCE SOCIETY; PREVALENCE; WOMEN; FIBROMYALGIA AB Aims of Study: The Bladder Pain Syndrome Committee of the International Consultation on Incontinence was assigned the task by the consultation of reviewing the syndrome, formerly known as interstitial cystitis, in a comprehensive fashion. This included the topics of definition, nomenclature, taxonomy, epidemiology, etiology, pathology, diagnosis, symptom scales, outcome assessment, principles of management, specific therapies, and future directions in research. Study Design, Materials, Methods: The emphasis was on new information developed since the last consultation 4 years previously. Where possible, existing evidence was assessed and a level of recommendation was developed according to the Oxford system of classification. Results: The consultation decided to refer to the condition as "bladder pain syndrome" (BPS) because the designation is more descriptive of the clinical condition and better fits standard classification taxonomy. Reasonable definitions of BPS include the definition of the ESSIC European group and a slight modification made at a SUFU sponsored Miami meeting in early 2008. Males or females with pain, pressure, or discomfort that they perceive to be related to the bladder with at least one urinary symptom, such as frequency not obviously related to high fluid intake, or a persistent urge to void should be evaluated for possible BPS. The initial assessment consists of a frequency/volume chart, focused physical examination, urinalysis, and urine culture. Urine cytology and cystoscopy are recommended if clinically indicated. Treatment progresses from conservative management through various oral and intravesical therapies, with most surgical therapies reserved for unresponsive cases. Pain management is critical throughout the treatment process. The consultation believes that the disorder is best viewed as one of a group of chronic pain syndromes, rather than as primarily an inflammatory bladder disorder. Recommendations for future research pathways are suggested. Neurourol. Urodynam. 29:191-198, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Hanno, Philip] Univ Penn, Philadelphia, PA 19104 USA. [Lin, Alex] Natl Yang Ming Univ, Taipei 112, Taiwan. [Nordling, Joergen] Univ Copenhagen, Herlev Hosp, DK-2730 Herlev, Denmark. [van Ophoven, Arndt] Univ Hosp Bochum, Marien Hosp, Herne, Germany. [Ueda, Tomohiro] Kyoto City Hosp, Dept Urol, Kyoto, Japan. [Wein, Alan] Univ Penn, Sch Med, Div Urol, Philadelphia, PA 19104 USA. [Nyberg, Leroy] NIDDKD, Urol Programs, Bethesda, MD 20892 USA. RP Hanno, P (reprint author), Hosp Univ Penn, 9 Penn Tower,3400 Spruce St, Philadelphia, PA 19194 USA. EM phil.hanno@uphs.upenn.edu NR 55 TC 79 Z9 81 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2010 VL 29 IS 1 BP 191 EP 198 DI 10.1002/nau.20847 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 541SB UT WOS:000273439200027 PM 20025029 ER PT J AU Kirby, AC Nager, CW Litman, HJ FitzGerald, MP Kraus, S Norton, P Sirls, L Rickey, L Wilson, T Dandreo, KJ Zimmern, P AF Kirby, A. C. Nager, C. W. Litman, H. J. FitzGerald, M. P. Kraus, S. Norton, P. Sirls, L. Rickey, L. Wilson, T. Dandreo, K. J. Zimmern, P. CA UIT N TI PREOPERATIVE VOIDING DETRUSOR PRESSURES AND STRESS INCONTINENCE SURGERY OUTCOMES SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT Joint Meeting of the International-Continence-Society/International-Urogynecological-Associat ion CY AUG 23-27, 2010 CL Toronto, CANADA SP Int Continence Soc, Int Urogynecol Assoc C1 [Kirby, A. C.; Nager, C. W.] Univ Calif San Diego, San Diego, CA 92103 USA. [FitzGerald, M. P.] Loyola Univ Med Ctr, Maywood, IL USA. [Kraus, S.] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Norton, P.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Sirls, L.] Beaumont Hosp, Med Ctr, Beaumont, TX USA. [Rickey, L.] Univ Maryland, College Pk, MD 20742 USA. [Wilson, T.] Univ Alabama, Birmingham, AL USA. [UIT N] NIH NIDDK, Bethesda, MD USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2010 VL 29 IS 6 MA 38 BP 860 EP 862 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 638OL UT WOS:000280904100039 ER PT B AU Merino, JG Hachinski, V AF Merino, Jose G. Hachinski, Vladimir BE Festa, JR Lazar, RM TI Historical Perspective SO NEUROVASCULAR NEUROPSYCHOLOGY LA English DT Article; Book Chapter ID DEMENTED OLD PEOPLE; VASCULAR DEMENTIA; ALZHEIMERS-DISEASE; BRAIN; BINSWANGER,OTTO; CRITERIA; STROKE C1 [Merino, Jose G.] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20824 USA. [Merino, Jose G.] Suburban Hosp, Stroke Program, Bethesda, MD USA. [Hachinski, Vladimir] Univ Western Ontario, Univ Hosp, London Hlth Sci Ctr, London, ON N6A 5A5, Canada. RP Merino, JG (reprint author), Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20824 USA. EM merinoj@ninds.nih.gov NR 54 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-6541-7 PY 2010 BP 1 EP 6 DI 10.1007/978-0-387-70715-0_1 PG 6 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA BSV22 UT WOS:000285894000001 ER PT B AU Launer, LJ Wright, C AF Launer, Lenore J. Wright, Clinton BE Festa, JR Lazar, RM TI Diabetes and Hypertension SO NEUROVASCULAR NEUROPSYCHOLOGY LA English DT Article; Book Chapter ID INSULIN-DEGRADING ENZYME; WHITE-MATTER LESIONS; MINI-MENTAL-STATE; RECURRENT SEVERE HYPOGLYCEMIA; NUTRITION EXAMINATION SURVEY; IMPAIRED GLUCOSE-TOLERANCE; POPULATION-BASED COHORT; MIDLIFE BLOOD-PRESSURE; CORONARY-HEART-DISEASE; 3RD NATIONAL-HEALTH C1 [Launer, Lenore J.] NIA, Neuroepidemiol Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Wright, Clinton] Univ Miami, Miller Sch Med, Evelyn F McKnight Ctr Age Related Memory Loss, Div Cognit Disorders,Dept Neurol, Miami, FL 33136 USA. RP Launer, LJ (reprint author), NIA, Neuroepidemiol Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov OI Wright, Clinton/0000-0002-9797-6215 NR 102 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-6541-7 PY 2010 BP 191 EP 202 DI 10.1007/978-0-387-70715-0_14 PG 12 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA BSV22 UT WOS:000285894000014 ER PT J AU Larkin, JD Frimat, KA Fyles, TM Flower, SE James, TD AF Larkin, Joseph D. Frimat, Karine A. Fyles, Thomas M. Flower, Stephen E. James, Tony D. TI Boronic acid based photoinduced electron transfer (PET) fluorescence sensors for saccharides SO NEW JOURNAL OF CHEMISTRY LA English DT Article ID CORRELATED MOLECULAR CALCULATIONS; GAUSSIAN-BASIS SETS; SIALYL-LEWIS-X; INTENSIVE TREATMENT; DIABETES-MELLITUS; RENAL GLYCOSURIA; WAVE-FUNCTIONS; GLUCOSE; RECEPTORS; PROGRESSION AB A simple three step synthesis was developed to provide six novel modular sensors, consisting of three para sensors, and three meta sensors with naphthalene, anthracene and pyrene fluorophores. The interaction of the six sensors with the saccharides: D-glucose, D-fructose, D-galactose, and D-mannose, were evaluated. All sensors displayed increasing fluorescence intensity upon the addition of these saccharides, with all of the sensors showing enhanced selectivity for D-glucose over D-galactose, D-fructose and D-mannose. High affinity (K-obs) was also observed for the meta sensors with respect to the para sensors. The naphthalene and anthracene meta sensors showed particularly high affinity (K-obs) for D-galactose. Circular dichroism spectroscopy was used to probe the structures of the complexes formed. Cyclic complexes were formed between all six sensors and D-glucose. Whilst naphthalene and anthracene meta sensors which displayed high affinity for D-galactose also formed cyclic complexes with that saccharide. C1 [Frimat, Karine A.; Flower, Stephen E.; James, Tony D.] Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England. [Larkin, Joseph D.] NHLBI, NIH, Bethesda, MD 20851 USA. [Fyles, Thomas M.] Univ Victoria, Dept Chem, Victoria, BC V8W 3V6, Canada. RP James, TD (reprint author), Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England. EM t.d.james@bath.ac.uk RI Flower, Stephen/B-3902-2010; James, Tony/B-5125-2009 OI Flower, Stephen/0000-0003-2659-3118; James, Tony/0000-0002-4095-2191 FU EPRSC [GR/M15217]; University of Bath FX TDJ thanks the EPRSC for a Research Grant (GR/M15217) and the University of Bath for support. NR 76 TC 16 Z9 16 U1 4 U2 40 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1144-0546 EI 1369-9261 J9 NEW J CHEM JI New J. Chem. PY 2010 VL 34 IS 12 BP 2922 EP 2931 DI 10.1039/c0nj00578a PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 684IY UT WOS:000284544800030 ER PT S AU Oakley, RH Cidlowski, JA AF Oakley, Robert H. Cidlowski, John A. BE Bunce, CM Campbell, MJ TI THE GLUCOCORTICOID RECEPTOR SO NUCLEAR RECEPTORS: CURRENT CONCEPTS AND FUTURE CHALLENGES SE Proteins and Cell Regulation LA English DT Article; Book Chapter ID NECROSIS-FACTOR-ALPHA; N-TERMINAL KINASE; PRE-MESSENGER-RNA; BETA-ISOFORM; RESPONSE ELEMENT; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; C-JUN; NUCLEAR RECEPTORS; GENE-EXPRESSION AB Glucocorticoids are essential for life and play critical roles in many diverse physiological processes including metabolism, development, growth, inflammation, and apoptosis. Drugs that mimic the actions of glucocorticoids are widely used to treat diseases such as cancer, inflammation, and autoimmune disorders. The effects of glucocorticoids and their synthetic derivatives are mediated by the glucocorticoid receptor (GR, NR3C1), a member of the nuclear receptor superfamily of ligand-dependent transcription factors. Upon binding hormone, the GR translocates into the nucleus where it regulates gene expression by direct binding to DNA and/or through interactions with other transcription factors. The GR is derived from a single gene, yet recent work has demonstrated that alternative processing of this gene generates an astonishing array of GR isoforms with unique expression, functional, and gene regulatory profiles. Here, we discuss the molecular and cellular mechanisms of GR signaling, and the potential role for GR isoforms in regulating the specificity and sensitivity of glucocorticoid responsiveness in healthy and diseased tissues. C1 [Oakley, Robert H.; Cidlowski, John A.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Oakley, RH (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov NR 153 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1567-2530 BN 978-90-481-3302-4 J9 PROTEINS CELL REGUL JI Proteins Cell Regul. PY 2010 VL 8 BP 63 EP 89 DI 10.1007/978-90-481-3303-1_4 D2 10.1007/978-90-481-3303-1 PG 27 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BOH92 UT WOS:000276683200004 ER PT S AU Vennstrom, B Liu, H Forrest, D AF Vennstrom, Bjorn Liu, Hong Forrest, Douglas BE Bunce, CM Campbell, MJ TI THYROID HORMONE RECEPTORS SO NUCLEAR RECEPTORS: CURRENT CONCEPTS AND FUTURE CHALLENGES SE Proteins and Cell Regulation LA English DT Article; Book Chapter ID THYROTROPIN-RELEASING-HORMONE; C-ERBA-ALPHA; MICE LACKING; XENOPUS-LAEVIS; GENE-EXPRESSION; RESPONSE ELEMENT; AMPHIBIAN METAMORPHOSIS; POSTNATAL-DEVELOPMENT; NULL MICE; TR-BETA AB Thyroid hormone promotes a diverse range of developmental, neurological and metabolic functions in vertebrate species. Human thyroid disorders result in a correspondingly wide range of disease symptoms. The functions of thyroid hormone are mediated by a small group of thyroid hormone receptors encoded by two conserved genes. Thyroid hormone receptors were among the first nuclear receptors to be identified and act as ligand-regulated transcription factors. These receptors are particularly versatile since they also have the potential to mediate ligand-independent transcriptional control. Genetic analyses have revealed both specific and overlapping roles for each receptor, revealing how a small receptor family can mediate an extended range of biological functions. C1 [Vennstrom, Bjorn] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. [Liu, Hong; Forrest, Douglas] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Vennstrom, B (reprint author), Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. EM Bjorn.Vennstrom@ki.se NR 130 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1567-2530 BN 978-90-481-3302-4 J9 PROTEINS CELL REGUL JI Proteins Cell Regul. PY 2010 VL 8 BP 183 EP 201 DI 10.1007/978-90-481-3303-1_7 D2 10.1007/978-90-481-3303-1 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BOH92 UT WOS:000276683200007 ER PT S AU Burd, CJ Archer, TK AF Burd, Craig J. Archer, Trevor K. BE Bunce, CM Campbell, MJ TI NUCLEAR RECEPTORS AND ATP DEPENDENT CHROMATIN REMODELING: A COMPLEX STORY SO NUCLEAR RECEPTORS: CURRENT CONCEPTS AND FUTURE CHALLENGES SE Proteins and Cell Regulation LA English DT Article; Book Chapter ID TRANSCRIPTION IN-VIVO; MEDIATES CRITICAL INTERACTIONS; THYROID-HORMONE RECEPTOR; RETINOIC ACID RECEPTOR; ACTIN-RELATED PROTEINS; TUMOR VIRUS PROMOTER; ESTROGEN-RECEPTOR; GLUCOCORTICOID-RECEPTOR; SACCHAROMYCES-CEREVISIAE; HISTONE DEACETYLASE AB Nuclear receptors are a class of tightly regulated and highly inducible transcription factors and thus represent an excellent model for the study of transcription. The activity of these transcription factors is controlled by their interactions with co-regulatory proteins that act to remodel chromatin, modify histones, and initiate the transcriptional process. This review will focus on the use of nuclear receptors in understanding the role of ATP-dependent chromatin remodeling enzymes in transcription. C1 [Burd, Craig J.; Archer, Trevor K.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. RP Burd, CJ (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. EM archer1@niehs.nih.gov OI Burd, Craig/0000-0002-6899-6751 NR 128 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1567-2530 BN 978-90-481-3302-4 J9 PROTEINS CELL REGUL JI Proteins Cell Regul. PY 2010 VL 8 BP 345 EP 363 DI 10.1007/978-90-481-3303-1_14 D2 10.1007/978-90-481-3303-1 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BOH92 UT WOS:000276683200014 ER PT J AU Baranello, L Bertozzi, D Fogli, MV Pommier, Y Capranico, G AF Baranello, Laura Bertozzi, Davide Fogli, Maria Vittoria Pommier, Yves Capranico, Giovanni TI DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1 alpha gene locus SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENOME-WIDE; HYPOXIA; DAMAGE; ELONGATION; ACTIVATION; EXPRESSION; COMPLEXES; MECHANISM; CELLS; DEGRADATION AB Top1 inhibition by camptothecin (CPT) perturbs RNA polymerase II (Pol II) density at promoters and along transcribed genes suggesting an involvement of Top1 in Pol II pausing. Here, we demonstrate that Top1 inhibition favors Pol II escape from a promoter-proximal pausing site of the human HIF-1 alpha gene in living cells. Interestingly, alternative splicing at exon 11 was markedly altered in nascent HIF-1 alpha mRNAs, and chromatin structure was also affected with enhanced histone acetylation and reduced nucleosome density in a manner dependent on cdk activity. Moreover, CPT increases transcription of a novel long RNA (5'aHIF1 alpha), antisense to human HIF-1 alpha mRNA, and a known antisense RNA at the 3'-end of the gene, while decreasing mRNA levels under normoxic and hypoxic conditions. The effects require Top1, but are independent from Top1-induced replicative DNA damage. Chromatin RNA immunoprecipitation results showed that CPT can activate antisense transcription mediated by cyclin-dependent kinase (cdk) activity. Thus, Top1 inhibition can trigger a transcriptional stress, involving antisense transcription and increased chromatin accessibility, which is dependent on cdk activity and deregulated Pol II pausing. A changed balance of antisense transcripts and mRNAs may then lead to altered regulation of HIF-1 alpha activity in human cancer cells. C1 [Baranello, Laura; Bertozzi, Davide; Fogli, Maria Vittoria; Capranico, Giovanni] Univ Bologna, G Moruzzi Dept Biochem, I-40126 Bologna, Italy. [Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Capranico, G (reprint author), Univ Bologna, G Moruzzi Dept Biochem, I-40126 Bologna, Italy. EM giovanni.capranico@unibo.it RI Capranico, Giovanni/K-1678-2014 OI Capranico, Giovanni/0000-0002-8708-6454 FU Associazione Italiana per la Ricerca sul Cancro [IG 4494]; Ministero dell'Universitae della Ricerca; University of Bologna FX Associazione Italiana per la Ricerca sul Cancro [IG 4494 to G. C.]. Ministero dell'Universitae della Ricerca (PRIN program) [to G. C.]. University of Bologna PhD Program in Functional Biology of Molecular and Cellular Systems [to L. B. and D. B.]. Funding for open access charge: Associazione Italiana per la Ricerca sul Cancro, Milan, Italy [IG 4494 to G. C.]. NR 43 TC 32 Z9 35 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 IS 1 BP 159 EP 171 DI 10.1093/nar/gkp817 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 539BT UT WOS:000273229100019 PM 19854946 ER PT J AU Kuwano, Y Pullmann, R Marasa, BS Abdelmohsen, K Lee, EK Yang, XL Martindale, JL Zhan, M Gorospe, M AF Kuwano, Yuki Pullmann, Rudolf, Jr. Marasa, Bernard S. Abdelmohsen, Kotb Lee, Eun Kyung Yang, Xiaoling Martindale, Jennifer L. Zhan, Ming Gorospe, Myriam TI NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POSTTRANSCRIPTIONAL GENE-REGULATION; BINDING PROTEINS HUR; ACTIVATED T-CELLS; EXPRESSION; PHOSPHORYLATION; IDENTIFICATION; PURIFICATION; STABILITY; CLONING; STABILIZATION AB The RNA-binding protein nuclear factor 90 (NF90) has been implicated in the stabilization, transport and translational control of several target mRNAs. However, a systematic analysis of NF90 target mRNAs has not been performed. Here, we use ribonucleoprotein immunoprecipitation analysis to identify a large subset of NF90-associated mRNAs. Comparison of the 3'-untranslated regions (UTRs) of these mRNAs led to the elucidation of a 25- to 30-nucleotide, RNA signature motif rich in adenines and uracils. Insertion of the AU-rich NF90 motif ('NF90m') in the 3'UTR of an EGFP heterologous reporter did not affect the steady-state level of the chimeric EGFP-NF90m mRNA or its cytosolic abundance. Instead, the translation of EGFP-NF90m mRNA was specifically repressed in an NF90-dependent manner, as determined by analysing nascent EGFP translation, the distribution of chimeric mRNAs on polysome gradients and the steady-state levels of expressed EGFP protein. The interaction of endogenous NF90 with target mRNAs was validated after testing both endogenous mRNAs and recombinant biotinylated transcripts containing NF90 motif hits. Further analysis showed that the stability of endogenous NF90 target mRNAs was not significantly influenced by NF90 abundance, while their translation increased when NF90 levels were reduced. In summary, we have identified an AU-rich RNA motif present in NF90 target mRNAs and have obtained evidence that NF90 represses the translation of this subset of mRNAs. C1 [Kuwano, Yuki; Pullmann, Rudolf, Jr.; Marasa, Bernard S.; Abdelmohsen, Kotb; Lee, Eun Kyung; Yang, Xiaoling; Martindale, Jennifer L.; Gorospe, Myriam] NIA, RNA Regulat Sect, Lab Cellular & Mol Biol, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Zhan, Ming] NIA, Bioinformat Unit, Res Resources Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, RNA Regulat Sect, Lab Cellular & Mol Biol, Intramural Res Program,NIH, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI abdelmohsen, Kotb/0000-0001-6240-5810 FU NIA-IRP; National Institute of Health FX Supported in its entirety by the NIA-IRP, National Institute of Health. Funding for open access charge: National Institute on Aging-Intramural Research Program, National Institutes of Health. NR 45 TC 48 Z9 49 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 IS 1 BP 225 EP 238 DI 10.1093/nar/gkp861 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 539BT UT WOS:000273229100025 PM 19850717 ER PT J AU Medrano, MS Policastro, PF Schwan, TG Coburn, J AF Medrano, Melisa S. Policastro, Paul F. Schwan, Tom G. Coburn, Jenifer TI Interaction of Borrelia burgdorferi Hbb with the p66 promoter SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LYME-DISEASE SPIROCHETE; OUTER SURFACE-PROTEINS; TICK INFECTIOUS CYCLE; GENE-EXPRESSION; IXODES-RICINUS; H-NS; DIFFERENTIAL EXPRESSION; ESCHERICHIA-COLI; DNA-BINDING; TRANSCRIPTIONAL ACTIVATOR AB Borrelia burgdorferi, an agent of Lyme disease, encodes the beta(3)-chain integrin ligand P66. P66 is expressed by B. burgdorferi in the mammal, in laboratory media, and as the bacteria are acquired or transmitted by the tick, but is not expressed by the bacterium in unfed ticks. Attempts to reveal factors influencing expression revealed that P66 was expressed in all in vitro conditions investigated. Candidate regulators identified in a search of the B. burgdorferi genome for homologs to other bacterial transcription factors were cloned and introduced into E. coli carrying a p66 promoter-signal sequence-phoA (alkaline phosphatase, or AP) fusion. Three candidate transcription factors-two that decreased AP activity (Hbb and BB0527), and one that increased AP activity (BBA23)-were identified. BBA23 and BB0527 did not bind to the p66 promoter at physiologically relevant concentrations. In contrast, several promoter fragments, including p66, were bound by Hbb (BB0232), with slightly different affinities. Consistent with results from other laboratories, Hbb appears to recognize multiple DNA sequences. Changes in the expression of p66 and bb0232 in the tick at various points with respect to feeding on mice, along with the results of the reporter experiment in the surrogate host E. coli, are consistent with Hbb/BB0232 being involved in regulating p66 expression. C1 [Medrano, Melisa S.; Coburn, Jenifer] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Policastro, Paul F.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, Hamilton, MT 59840 USA. [Coburn, Jenifer] Tufts Univ, Sch Med, Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 USA. [Coburn, Jenifer] Med Coll Wisconsin, Div Infect Dis, Ctr Biopreparedness & Infect Dis, Milwaukee, WI 53226 USA. RP Coburn, J (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. EM jcoburn@mcw.edu FU National Institutes of Health [R01 AI51407, R01 AI059505, T32-AI-07422, F31 AI52495]; Division of Intramural Research; National Institutes of Allergy and Infectious Diseases, National Institutes of Health; National Institutes of Diabetes and Digestive and Kidney Diseases [P30DK39428] FX National Institutes of Health (grant R01 AI51407 and R01 AI059505 to J. C.); National Institutes of Health training (grant T32-AI-07422 and F31 AI52495, partial); Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (to T. G. S. and P. F. P.). Funding for open access charge: National Institutes of Health grant. We are grateful for the support of Anne Kane, MD and the Tufts- NEMC Center for Gastroenterology Research on Absorptive and Secretory Processes funded by a grant from National Institutes of Diabetes and Digestive and Kidney Diseases (P30DK39428). NR 92 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 IS 2 BP 414 EP 427 DI 10.1093/nar/gkp1027 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 549XW UT WOS:000274088800013 PM 19910373 ER PT J AU Akagi, K Stephens, RM Li, JF Evdokimov, E Kuehn, MR Volfovsky, N Symer, DE AF Akagi, Keiko Stephens, Robert M. Li, Jingfeng Evdokimov, Evgenji Kuehn, Michael R. Volfovsky, Natalia Symer, David E. TI MouseIndelDB: a database integrating genomic indel polymorphisms that distinguish mouse strains SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INSERTION-DELETION POLYMORPHISMS; COPY NUMBER VARIATION; GENETIC-VARIATION; TRANSPOSABLE ELEMENTS; STRUCTURAL VARIATION; LABORATORY MOUSE; MAP; RESOURCES; HUMANS; SNPS AB MouseIndelDB is an integrated database resource containing thousands of previously unreported mouse genomic indel (insertion and deletion) polymorphisms ranging from similar to 100 nt to 10Kb in size. The database currently includes polymorphisms identified from our alignment of 26 million whole-genome shotgun sequence traces from four laboratory mouse strains mapped against the reference C57BL/6J genome using GMAP. They can be queried on a local level by chromosomal coordinates, nearby gene names or other genomic feature identifiers, or in bulk format using categories including mouse strain(s), class of polymorphism(s) and chromosome number. The results of such queries are presented either as a custom track on the UCSC mouse genome browser or in tabular format. We anticipate that the MouseIndelDB database will be widely useful for research in mammalian genetics, genomics, and evolutionary biology. Access to the MouseIndelDB database is freely available at: http://variation.osu.edu/. C1 [Akagi, Keiko; Li, Jingfeng; Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Akagi, Keiko] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Stephens, Robert M.; Volfovsky, Natalia] SAIC Frederick Inc, NCI Frederick, Adv Biomed Comp Ctr, Informat Syst Program, Frederick, MD 21702 USA. [Li, Jingfeng; Symer, David E.] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Evdokimov, Evgenji; Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA. [Symer, David E.] NCI, Lab Biochem & Mol Biol, Ctr Canc Res, Frederick, MD 21702 USA. [Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. [Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. [Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Dept Biomed Informat, Columbus, OH 43210 USA. RP Symer, DE (reprint author), Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. EM stephensr@mail.nih.gov; david.symer@osumc.edu RI Symer, David/E-4173-2011; Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Ohio State University Comprehensive Cancer Center FX The National Cancer Institute, National Institutes of Health (under contract N01-CO-12400); the Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health; and The Ohio State University Comprehensive Cancer Center. Funding for open access charge: The Ohio State University Comprehensive Cancer Center. NR 43 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D600 EP D606 DI 10.1093/nar/gkp1046 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100096 PM 19933259 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Sayers, EW AF Benson, Dennis A. Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Sayers, Eric W. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE AB GenBank(R) is a comprehensive database that contains publicly available nucleotide sequences for more than 300 000 organisms named at the genus level or lower, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bi-monthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI homepage: www.ncbi.nlm.nih.gov. C1 [Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov FU National Institutes of Health; National Library of Medicine FX Funding for open access charge: The Intramural Research Program of the National Institutes of Health; National Library of Medicine. NR 12 TC 204 Z9 207 U1 1 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D46 EP D51 DI 10.1093/nar/gkp1024 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100007 PM 19910366 ER PT J AU Brinkac, LM Davidsen, T Beck, E Ganapathy, A Caler, E Dodson, RJ Durkin, AS Harkins, DM Lorenzi, H Madupu, R Sebastian, Y Shrivastava, S Thiagarajan, M Orvis, J Sundaram, JP Crabtree, J Galens, K Zhao, YM Inman, JM Montgomery, R Schobel, S Galinsky, K Tanenbaum, DM Resnick, A Zafar, N White, O Sutton, G AF Brinkac, Lauren M. Davidsen, Tanja Beck, Erin Ganapathy, Anuradha Caler, Elisabet Dodson, Robert J. Durkin, A. Scott Harkins, Derek M. Lorenzi, Hernan Madupu, Ramana Sebastian, Yinong Shrivastava, Susmita Thiagarajan, Mathangi Orvis, Joshua Sundaram, Jaideep P. Crabtree, Jonathon Galens, Kevin Zhao, Yongmei Inman, Jason M. Montgomery, Robert Schobel, Seth Galinsky, Kevin Tanenbaum, David M. Resnick, Adam Zafar, Nikhat White, Owen Sutton, Granger TI Pathema: a clade-specific bioinformatics resource center for pathogen research SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ENTAMOEBA-HISTOLYTICA; BURKHOLDERIA-MALLEI; CDC CATEGORY; SYSTEM; PROTEIN; TOOL; AGENTS; GLANDERS; SOFTWARE; DATABASE AB Pathema (http://pathema.jcvi.org) is one of the eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infectious Disease (NIAID) designed to serve as a core resource for the bio-defense and infectious disease research community. Pathema strives to support basic research and accelerate scientific progress for understanding, detecting, diagnosing and treating an established set of six target NIAID Category A-C pathogens: Category A priority pathogens; Bacillus anthracis and Clostridium botulinum, and Category B priority pathogens; Burkholderia mallei, Burkholderia pseudomallei, Clostridium perfringens and Entamoeba histolytica. Each target pathogen is represented in one of four distinct clade-specific Pathema web resources and underlying databases developed to target the specific data and analysis needs of each scientific community. All publicly available complete genome projects of phylogenetically related organisms are also represented, providing a comprehensive collection of organisms for comparative analyses. Pathema facilitates the scientific exploration of genomic and related data through its integration with web-based analysis tools, customized to obtain, display, and compute results relevant to ongoing pathogen research. Pathema serves the bio-defense and infectious disease research community by disseminating data resulting from pathogen genome sequencing projects and providing access to the results of inter-genomic comparisons for these organisms. C1 [Brinkac, Lauren M.; Davidsen, Tanja; Beck, Erin; Caler, Elisabet; Dodson, Robert J.; Durkin, A. Scott; Harkins, Derek M.; Lorenzi, Hernan; Madupu, Ramana; Sebastian, Yinong; Shrivastava, Susmita; Thiagarajan, Mathangi; Sundaram, Jaideep P.; Inman, Jason M.; Montgomery, Robert; Schobel, Seth; Galinsky, Kevin; Tanenbaum, David M.; Resnick, Adam; Zafar, Nikhat; Sutton, Granger] J Craig Venter Inst, Rockville, MD 20850 USA. [Dodson, Robert J.] Northwestern Univ, Evanston, IL 60208 USA. [Sebastian, Yinong] NIAID, NIH, Bethesda, MD 20892 USA. [Orvis, Joshua; Crabtree, Jonathon; Galens, Kevin; Zhao, Yongmei; White, Owen] Univ Maryland, Inst Genome Sci, Sch Med, Baltimore, MD 21201 USA. [Zhao, Yongmei] NCI, SAIC, Gaithersburg, MD 20877 USA. RP Sutton, G (reprint author), J Craig Venter Inst, Rockville, MD 20850 USA. EM gsutton@jcvi.org FU National Institute of Allergy and Infectious Disease [HHSN266200400038C] FX National Institute of Allergy and Infectious Disease contract HHSN266200400038C. Funding for open access charge: NIAID. NR 46 TC 14 Z9 14 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D408 EP D414 DI 10.1093/nar/gkp850 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100064 PM 19843611 ER PT J AU Cochrane, GR Galperin, MY AF Cochrane, Guy R. Galperin, Michael Y. TI The 2010 Nucleic Acids Research Database Issue and online Database Collection: a community of data resources SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MINIMUM INFORMATION; GENOME SEQUENCE AB The current issue of Nucleic Acids Research includes descriptions of 58 new and 73 updated data resources. The accompanying online Database Collection, available at http://www.oxfordjournals.org/nar/database/a/, now lists 1230 carefully selected databases covering various aspects of molecular and cell biology. While most data resource descriptions remain very brief, the issue includes several longer papers that highlight recent significant developments in such databases as Pfam, MetaCyc, UniProt, ELM and PDBe. The databases described in the Database Issue and Database Collection, however, are far more than a distinct set of resources; they form a network of connected data, concepts and shared technology. The full content of the Database Issue is available online at the Nucleic Acids Research web site (http://nar.oxfordjournals.org/). C1 [Cochrane, Guy R.] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England. [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Cochrane, GR (reprint author), EMBL European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. EM cochrane@ebi.ac.uk RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Cochrane, Guy/0000-0001-7954-7057 FU European Molecular Biology Laboratory; US National Institutes of Health; Oxford University Press FX European Molecular Biology Laboratory (to G. R. C.); Intramural Research Program of the US National Institutes of Health (to M. Y. G.). Funding for open access charge: Oxford University Press. NR 30 TC 48 Z9 50 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D1 EP D4 DI 10.1093/nar/gkp1077 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100001 PM 19965766 ER PT J AU Geer, LY Marchler-Bauer, A Geer, RC Han, LY He, J He, SQ Liu, CL Shi, WY Bryant, SH AF Geer, Lewis Y. Marchler-Bauer, Aron Geer, Renata C. Han, Lianyi He, Jane He, Siqian Liu, Chunlei Shi, Wenyao Bryant, Stephen H. TI The NCBI BioSystems database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PATHWAY; INFORMATION; RESOURCES; BIOLOGY AB The NCBI BioSystems database, found at http://www.ncbi.nlm.nih.gov/biosystems/, centralizes and cross-links existing biological systems databases, increasing their utility and target audience by integrating their pathways and systems into NCBI resources. This integration allows users of NCBI's Entrez databases to quickly categorize proteins, genes and small molecules by metabolic pathway, disease state or other BioSystem type, without requiring time-consuming inference of biological relationships from the literature or multiple experimental datasets. C1 [Geer, Lewis Y.; Marchler-Bauer, Aron; Geer, Renata C.; Han, Lianyi; He, Jane; He, Siqian; Liu, Chunlei; Shi, Wenyao; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Geer, LY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM lewis.geer@nih.gov; bauer@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 FU National Library of Medicine at National Institutes of Health/DHHS FX Intramural Research Program of the National Library of Medicine at National Institutes of Health/DHHS. Funding for open access charge: Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS. NR 13 TC 181 Z9 183 U1 6 U2 35 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D492 EP D496 DI 10.1093/nar/gkp858 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100079 PM 19854944 ER PT J AU Ji, L Barrett, T Ayanbule, O Troup, DB Rudnev, D Muertter, RN Tomashevsky, M Soboleva, A Slotta, DJ AF Ji, Li Barrett, Tanya Ayanbule, Oluwabukunmi Troup, Dennis B. Rudnev, Dmitry Muertter, Rolf N. Tomashevsky, Maxim Soboleva, Alexandra Slotta, Douglas J. TI NCBI Peptidome: a new repository for mass spectrometry proteomics data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PUBLIC REPOSITORY; PROTEIN; IDENTIFICATIONS AB Peptidome is a public repository that archives and freely distributes tandem mass spectrometry peptide and protein identification data generated by the scientific community. Data from all stages of a mass spectrometry experiment are captured, including original mass spectra files, experimental metadata and conclusion-level results. The submission process is facilitated through acceptance of data in commonly used open formats, and all submissions undergo syntactic validation and curation in an effort to uphold data integrity and quality. Peptidome is not restricted to specific organisms, instruments or experiment types; data from any tandem mass spectrometry experiment from any species are accepted. In addition to data storage, web-based interfaces are available to help users query, browse and explore individual peptides, proteins or entire Samples and Studies. Results are integrated and linked with other NCBI resources to ensure dissemination of the information beyond the mass spectroscopy proteomics community. Peptidome is freely accessible at http://www.ncbi.nlm.nih.gov/peptidome. C1 [Ji, Li; Barrett, Tanya; Ayanbule, Oluwabukunmi; Troup, Dennis B.; Rudnev, Dmitry; Muertter, Rolf N.; Tomashevsky, Maxim; Soboleva, Alexandra; Slotta, Douglas J.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Slotta, DJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM slottad@ncbi.nlm.nih.gov FU National Institutes of Health; National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 9 TC 14 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D731 EP D735 DI 10.1093/nar/gkp1047 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100115 PM 19942688 ER PT J AU Kim, HS Murphy, T Xia, J Caragea, D Park, Y Beeman, RW Lorenzen, MD Butcher, S Manak, JR Brown, SJ AF Kim, Hee Shin Murphy, Terence Xia, Jing Caragea, Doina Park, Yoonseong Beeman, Richard W. Lorenzen, Marce D. Butcher, Stephen Manak, J. Robert Brown, Susan J. TI BeetleBase in 2010: revisions to provide comprehensive genomic information for Tribolium castaneum SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENERATION; DATABASE; BLAST AB BeetleBase (http://www.beetlebase.org) has been updated to provide more comprehensive genomic information for the red flour beetle Tribolium castaneum. The database contains genomic sequence scaffolds mapped to 10 linkage groups (genome assembly release Tcas_ 3.0), genetic linkage maps, the official gene set, Reference Sequences from NCBI (RefSeq), predicted gene models, ESTs and whole-genome tiling array data representing several developmental stages. The database was reconstructed using the upgraded Generic Model Organism Database (GMOD) modules. The genomic data is stored in a PostgreSQL relatational database using the Chado schema and visualized as tracks in GBrowse. The updated genetic map is visualized using the comparative genetic map viewer CMAP. To enhance the database search capabilities, the BLAST and BLAT search tools have been integrated with the GMOD tools. BeetleBase serves as a long-term repository for Tribolium genomic data, and is compatible with other model organism databases. C1 [Kim, Hee Shin; Caragea, Doina; Brown, Susan J.] Kansas State Univ, Div Biol, Bioinformat Ctr, Manhattan, KS 66506 USA. [Murphy, Terence] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Xia, Jing; Caragea, Doina] Kansas State Univ, Dept Comp & Informat Sci, Manhattan, KS 66506 USA. [Park, Yoonseong] Kansas State Univ, Dept Entomol, Manhattan, KS 66506 USA. [Beeman, Richard W.; Lorenzen, Marce D.] USDA ARS, Grain Mkt & Prod Res Ctr, Manhattan, KS 66502 USA. [Butcher, Stephen; Manak, J. Robert] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA. [Manak, J. Robert] Univ Iowa, Roy J Carver Ctr Genom, Iowa City, IA 52242 USA. RP Brown, SJ (reprint author), Kansas State Univ, Div Biol, Bioinformat Ctr, Manhattan, KS 66506 USA. EM sjbrown@ksu.edu RI Park, Yoonseong/J-5861-2013 OI Park, Yoonseong/0000-0003-1191-7335 FU National Center for Research Resources (NCRR) [P20 RR016475]; National Institutes of Health; NIH; National Library of Medicine; National Center for Research Resources National Institutes of Health [P20 RR016475] FX Grant number P20 RR016475 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health. Work at NCBI was supported by the Intramural Research Program of the NIH, National Library of Medicine. Funding for open access charge: National Center for Research Resources National Institutes of Health (P20 RR016475). NR 12 TC 71 Z9 73 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D437 EP D442 DI 10.1093/nar/gkp807 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100069 PM 19820115 ER PT J AU Lobanov, MY Shoemaker, BA Garbuzynskiy, SO Fong, JH Panchenko, AR Galzitskaya, OV AF Lobanov, Michail Yu. Shoemaker, Benjamin A. Garbuzynskiy, Sergiy O. Fong, Jessica H. Panchenko, Anna R. Galzitskaya, Oxana V. TI ComSin: database of protein structures in bound (complex) and unbound (single) states in relation to their intrinsic disorder SO NUCLEIC ACIDS RESEARCH LA English DT Article ID UNSTRUCTURED PROTEINS; BINDING; ENTROPY; DOMAIN; RECOGNITION; SEQUENCES; DYNAMICS; FEATURES AB Most of the proteins in a cell assemble into complexes to carry out their function. In this work, we have created a new database (named ComSin) of protein structures in bound (complex) and unbound (single) states to provide a researcher with exhaustive information on structures of the same or homologous proteins in bound and unbound states. From the complete Protein Data Bank (PDB), we selected 24 910 pairs of protein structures in bound and unbound states, and identified regions of intrinsic disorder. For 2448 pairs, the proteins in bound and unbound states are identical, while 7129 pairs have sequence identity 90% or larger. The developed server enables one to search for proteins in bound and unbound states with several options including sequence similarity between the corresponding proteins in bound and unbound states, and validation of interaction interfaces of protein complexes. Besides that, through our web server, one can obtain necessary information for studying disorder-to-order and order-to-disorder transitions upon complex formation, and analyze structural differences between proteins in bound and unbound states. The database is available at http://antares.protres.ru/comsin/. C1 [Lobanov, Michail Yu.; Garbuzynskiy, Sergiy O.; Galzitskaya, Oxana V.] Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. [Shoemaker, Benjamin A.; Fong, Jessica H.; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Galzitskaya, OV (reprint author), Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. EM ogalzit@vega.protres.ru RI GALZITSKAYA, OXANA/L-2664-2015 FU Russian Foundation for Basic Research [08-04-00561]; Russian Science Support Foundation; Federal Agency for Science and Innovation [02.740.11.0295]; NIH, National Library of Medicine FX S. H. Programs 'Molecular and Cellular Biology' and 'Fundamental Sciences-medicine' by the Russian Foundation for Basic Research (08-04-00561); Russian Science Support Foundation; Federal Agency for Science and Innovation (grant # 02.740.11.0295); Intramural Research Program of the NIH, National Library of Medicine. Funding for open access charge: Intramural Research Program of the NIH, National Library of Medicine. NR 30 TC 16 Z9 16 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D283 EP D287 DI 10.1093/nar/gkp963 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100043 PM 19906708 ER PT J AU Sayers, EW Barrett, T Benson, DA Bolton, E Bryant, SH Canese, K Chetvernin, V Church, DM DiCuccio, M Federhen, S Feolo, M Geer, LY Helmberg, W Kapustin, Y Landsman, D Lipman, DJ Lu, ZY Madden, TL Madej, T Maglott, DR Marchler-Bauer, A Miller, V Mizrachi, I Ostell, J Panchenko, A Pruitt, KD Schuler, GD Sequeira, E Sherry, ST Shumway, M Sirotkin, K Slotta, D Souvorov, A Starchenko, G Tatusova, TA Wagner, L Wang, YL Wilbur, WJ Yaschenko, E Ye, J AF Sayers, Eric W. Barrett, Tanya Benson, Dennis A. Bolton, Evan Bryant, Stephen H. Canese, Kathi Chetvernin, Vyacheslav Church, Deanna M. DiCuccio, Michael Federhen, Scott Feolo, Michael Geer, Lewis Y. Helmberg, Wolfgang Kapustin, Yuri Landsman, David Lipman, David J. Lu, Zhiyong Madden, Thomas L. Madej, Tom Maglott, Donna R. Marchler-Bauer, Aron Miller, Vadim Mizrachi, Ilene Ostell, James Panchenko, Anna Pruitt, Kim D. Schuler, Gregory D. Sequeira, Edwin Sherry, Stephen T. Shumway, Martin Sirotkin, Karl Slotta, Douglas Souvorov, Alexandre Starchenko, Grigory Tatusova, Tatiana A. Wagner, Lukas Wang, Yanli Wilbur, W. John Yaschenko, Eugene Ye, Jian TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ONLINE MENDELIAN INHERITANCE; PROTEIN SEQUENCES; SEARCH; SYSTEM; ENTREZ; NCBI; GENES; SIMILARITIES; CHROMOSOMES; ANNOTATION AB In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, Reference Sequence, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, Retroviral Geno-typing Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Entrez Probe, GENSAT, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool, Biosystems, Peptidome, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov. C1 [Sayers, Eric W.; Barrett, Tanya; Benson, Dennis A.; Bolton, Evan; Bryant, Stephen H.; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M.; DiCuccio, Michael; Federhen, Scott; Feolo, Michael; Geer, Lewis Y.; Kapustin, Yuri; Landsman, David; Lipman, David J.; Lu, Zhiyong; Madden, Thomas L.; Madej, Tom; Maglott, Donna R.; Marchler-Bauer, Aron; Miller, Vadim; Mizrachi, Ilene; Ostell, James; Panchenko, Anna; Pruitt, Kim D.; Schuler, Gregory D.; Sequeira, Edwin; Sherry, Stephen T.; Shumway, Martin; Sirotkin, Karl; Slotta, Douglas; Souvorov, Alexandre; Starchenko, Grigory; Tatusova, Tatiana A.; Wagner, Lukas; Wang, Yanli; Wilbur, W. John; Yaschenko, Eugene; Ye, Jian] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Helmberg, Wolfgang] Med Univ Graz, Univ Clin Blood Grp Serol & Transfus Med, A-8036 Graz, Austria. RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712; Landsman, David/0000-0002-9819-6675 FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 53 TC 262 Z9 270 U1 2 U2 32 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D5 EP D16 DI 10.1093/nar/gkp967 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100002 PM 19910364 ER PT J AU Schriml, LM Arze, C Nadendla, S Ganapathy, A Felix, V Mahurkar, A Phillippy, K Gussman, A Angiuoli, S Ghedin, E White, O Hall, N AF Schriml, Lynn M. Arze, Cesar Nadendla, Suvarna Ganapathy, Anu Felix, Victor Mahurkar, Anup Phillippy, Katherine Gussman, Aaron Angiuoli, Sam Ghedin, Elodie White, Owen Hall, Neil TI GeMInA, Genomic Metadata for Infectious Agents, a geospatial surveillance pathogen database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SYSTEM AB The Gemina system (http://gemina.igs.umaryland.edu) identifies, standardizes and integrates the outbreak metadata for the breadth of NIAID category A-C viral and bacterial pathogens, thereby providing an investigative and surveillance tool describing the Who [Host], What [Disease, Symptom], When [Date], Where [Location] and How [Pathogen, Environmental Source, Reservoir, Transmission Method] for each pathogen. The Gemina database will provide a greater understanding of the interactions of viral and bacterial pathogens with their hosts and infectious diseases through in-depth literature text-mining, integrated outbreak metadata, outbreak surveillance tools, extensive ontology development, metadata curation and representative genomic sequence identification and standards development. The Gemina web interface provides metadata selection and retrieval of a pathogen's Infection Systems (Pathogen, Host, Disease, Transmission Method and Anatomy) and Incidents (Location and Date) along with a hosts Age and Gender. The Gemina system provides an integrated investigative and geospatial surveillance system connecting pathogens, pathogen products and disease anchored on the taxonomic ID of the pathogen and host to identify the breadth of hosts and diseases known for these pathogens, to identify the extent of outbreak locations, and to identify unique genomic regions with the DNA Signature Insignia Detection Tool. C1 [Schriml, Lynn M.; Arze, Cesar; Nadendla, Suvarna; Ganapathy, Anu; Felix, Victor; Mahurkar, Anup; Gussman, Aaron; Angiuoli, Sam; White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Phillippy, Katherine] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Ghedin, Elodie] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA USA. [Hall, Neil] Univ Liverpool, Sch Biol Sci, Liverpool L69 3BX, Merseyside, England. RP Schriml, LM (reprint author), Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. EM lschriml@som.umaryland.edu RI Hall, Neil/A-8717-2013; Angiuoli, Samuel/H-7340-2014; OI Hall, Neil/0000-0002-7995-3810; Angiuoli, Samuel/0000-0001-9525-4350; Hall, Neil/0000-0003-2808-0009; Schriml, Lynn/0000-0001-8910-9851 FU US Department of Homeland Security Science and Technology Directorate [W81XWH-05-2-005, NBCH2070002]; Institute for Genome Sciences FX US Department of Homeland Security Science and Technology Directorate. [W81XWH-05-2-005, NBCH2070002]. Funding for open access charge: Institute for Genome Sciences. NR 10 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D754 EP D764 DI 10.1093/nar/gkp832 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100119 PM 19850722 ER PT J AU Shoemaker, BA Zhang, DC Thangudu, RR Tyagi, M Fong, JH Marchler-Bauer, A Bryant, SH Madej, T Panchenko, AR AF Shoemaker, Benjamin A. Zhang, Dachuan Thangudu, Ratna R. Tyagi, Manoj Fong, Jessica H. Marchler-Bauer, Aron Bryant, Stephen H. Madej, Thomas Panchenko, Anna R. TI Inferred Biomolecular Interaction Server-a web server to analyze and predict protein interacting partners and binding sites SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ENTREZS 3D-STRUCTURE DATABASE; LIGAND-BINDING; FUNCTIONAL ANNOTATION; DOMAIN; INFORMATION; IDENTIFICATION; INTEROLOGS; SEQUENCES; SURFACE; GENOME AB IBIS is the NCBI Inferred Biomolecular Interaction Server. This server organizes, analyzes and predicts interaction partners and locations of binding sites in proteins. IBIS provides annotations for different types of binding partners (protein, chemical, nucleic acid and peptides), and facilitates the mapping of a comprehensive biomolecular interaction network for a given protein query. IBIS reports interactions observed in experimentally determined structural complexes of a given protein, and at the same time IBIS infers binding sites/interacting partners by inspecting protein complexes formed by homologous proteins. Similar binding sites are clustered together based on their sequence and structure conservation. To emphasize biologically relevant binding sites, several algorithms are used for verification in terms of evolutionary conservation, biological importance of binding partners, size and stability of interfaces, as well as evidence from the published literature. IBIS is updated regularly and is freely accessible via http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.html. C1 [Shoemaker, Benjamin A.; Zhang, Dachuan; Thangudu, Ratna R.; Tyagi, Manoj; Fong, Jessica H.; Marchler-Bauer, Aron; Bryant, Stephen H.; Madej, Thomas; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Madej, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM madej@ncbi.nlm.nih.gov; panch@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; Tyagi, Manoj/K-8438-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 FU National Institutes of Health/DHHS FX National Institutes of Health/DHHS (Intramural Research program of the National Library of Medicine). Funding for open access charge: National Institutes of Health/DHHS (Intramural Research program of the National Library of Medicine). NR 34 TC 42 Z9 42 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D518 EP D524 DI 10.1093/nar/gkp842 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100084 PM 19843613 ER PT J AU Shumway, M Cochrane, G Sugawara, H AF Shumway, Martin Cochrane, Guy Sugawara, Hideaki TI Archiving next generation sequencing data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BIOTECHNOLOGY INFORMATION; NATIONAL CENTER; RESOURCES AB Next generation sequencing platforms are producing biological sequencing data in unprecedented amounts. The partners of the International Nucleotide Sequencing Database Collaboration, which includes the National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EBI), and the DNA Data Bank of Japan (DDBJ), have established the Sequence Read Archive (SRA) to provide the scientific community with an archival destination for next generation data sets. The SRA is now accessible at http://www.ncbi.nlm.nih.gov/Traces/sra from NCBI, at http://www.ebi.ac.uk/ena from EBI and at http://www.ddbj.nig.ac.jp/sub/trace_sra-e.html from DDBJ. Users of these resources can obtain data sets deposited in any of the three SRA instances. Links and submission instructions are provided. C1 [Shumway, Martin] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Cochrane, Guy] EMBL European Bioinformat Inst, Cambridge, England. [Sugawara, Hideaki] Corp Res Org Informat & Syst, Interuniv Res Inst, Natl Inst Genet, DNA Data Bank Japan, Shizuoka, Japan. RP Shumway, M (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM shumwaym@ncbi.nlm.nih.gov OI Cochrane, Guy/0000-0001-7954-7057 FU Wellcome Trust; European Commission; European Molecular Biology Laboratory; Ministry of Education, Culture, Sports, Science and Technology of Japan FX The EBI's next generation sequence archiving activities are supported by the Wellcome Trust, the European Commission and the European Molecular Biology Laboratory. DDBJ's work on SRA and Trace Archive is supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan. Funding for open access charge: NCBI's SRA work was supported by the Intramural Research Program of the NIH, National Library of Medicine. NR 5 TC 49 Z9 52 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D870 EP D871 DI 10.1093/nar/gkp1078 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100135 PM 19965774 ER PT J AU Wang, YL Bolton, E Dracheva, S Karapetyan, K Shoemaker, BA Suzek, TO Wang, JY Xiao, JW Zhang, J Bryant, SH AF Wang, Yanli Bolton, Evan Dracheva, Svetlana Karapetyan, Karen Shoemaker, Benjamin A. Suzek, Tugba O. Wang, Jiyao Xiao, Jewen Zhang, Jian Bryant, Stephen H. TI An overview of the PubChem BioAssay resource SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NIH ROADMAP; DATABASE; INFORMATION; DISCOVERY; TOOL AB The PubChem BioAssay database (http://pubchem.ncbi.nlm.nih.gov) is a public repository for biological activities of small molecules and small interfering RNAs (siRNAs) hosted by the US National Institutes of Health (NIH). It archives experimental descriptions of assays and biological test results and makes the information freely accessible to the public. A PubChem BioAssay data entry includes an assay description, a summary and detailed test results. Each assay record is linked to the molecular target, whenever possible, and is cross-referenced to other National Center for Biotechnology Information (NCBI) database records. 'Related BioAssays' are identified by examining the assay target relationship and activity profile of commonly tested compounds. A key goal of PubChem BioAssay is to make the biological activity information easily accessible through the NCBI information retrieval system-Entrez, and various web-based PubChem services. An integrated suite of data analysis tools are available to optimize the utility of the chemical structure and biological activity information within PubChem, enabling researchers to aggregate, compare and analyze biological test results contributed by multiple organizations. In this work, we describe the PubChem BioAssay database, including data model, bioassay deposition and utilities that PubChem provides for searching, downloading and analyzing the biological activity information contained therein. C1 [Wang, Yanli; Bolton, Evan; Dracheva, Svetlana; Karapetyan, Karen; Shoemaker, Benjamin A.; Suzek, Tugba O.; Wang, Jiyao; Xiao, Jewen; Zhang, Jian; Bryant, Stephen H.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov RI Suzek, Tugba/B-6943-2015; OI Suzek, Tugba/0000-0002-3243-1759 FU National Institutes of Health FX Intramural Research program of the National Institutes of Health. NR 23 TC 151 Z9 152 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 SU 1 BP D255 EP D266 DI 10.1093/nar/gkp965 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 579TV UT WOS:000276399100039 PM 19933261 ER PT J AU Quinn, AM Bedford, MT Espejo, A Spannhoff, A Austin, CP Oppermann, U Simeonov, A AF Quinn, Amy M. Bedford, Mark T. Espejo, Alexsandra Spannhoff, Astrid Austin, Christopher P. Oppermann, Udo Simeonov, Anton TI A homogeneous method for investigation of methylation-dependent protein-protein interactions in epigenetics SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HP1 CHROMO DOMAIN; HISTONE H3 TAIL; LYSINE-4 METHYLATION; DNA METHYLATION; CANCER; RECOGNITION; METHYLTRANSFERASES; CHROMODOMAINS; TRANSCRIPTION; IMMUNOASSAY AB Methylation of lysine residues on the tails of histone proteins is a major determinant of the transcription state of associated DNA coding regions. The interplay among methylation states and other histone modifications to direct transcriptional outcome is referred to as the histone code. In addition to histone methyltransferases and demethylases which function to modify the methylation state of lysine sidechains, other proteins recognize specific histone methylation marks essentially serving as code readers. While these interactions are highly specific with respect to site and methylation state of particular lysine residues, they are generally weak and therefore difficult to monitor by traditional assay techniques. Herein, we present the design and implementation of a homogeneous, miniaturizable, and sensitive assay for histone methylation-dependent interactions. We use AlphaScreen, a chemiluminescence-based technique, to monitor the interactions of chromodomains (MPP8, HP1 beta and CHD1), tudor domains (JMJD2A) and plant homeodomains (RAG2) with their cognate trimethyllysine histone partners. The utility of the method was demonstrated by profiling the binding specificities of chromo- and tudor domains toward several histone marks. The simplicity of design and the sensitive and robust nature of this assay should make it applicable to a range of epigenetic studies, including the search for novel inhibitors of methylation-dependent interactions. C1 [Quinn, Amy M.; Austin, Christopher P.; Simeonov, Anton] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Bedford, Mark T.; Espejo, Alexsandra; Spannhoff, Astrid] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA. [Oppermann, Udo] Univ Oxford, Struct Genom Consortium, Headington OX3 7DQ, England. [Oppermann, Udo] Botnar Res Ctr, Oxford Biomed Res Unit, Oxford OX3 7LD, England. RP Simeonov, A (reprint author), NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. EM asimeono@mail.nih.gov RI Bedford, Mark/E-7856-2011; OI Espejo, Alexsandra/0000-0002-8841-7219 FU The Molecular Libraries Initiative of the NIH Roadmap for Medical Research; NHGRI, NIH; Welch Foundation Grant [G-1495]; NIDA [DA025800, P30ES007784]; The German Research Foundation [SP1262/1-1]; The Structural Genomics Consortium is a registered charity [1097737]; Canadian Institutes for Health Research; Canadian Foundation for Innovation; Genome Canada; Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust; NIH Roadmap for Medical Research, National Institutes of Health FX The Molecular Libraries Initiative of the NIH Roadmap for Medical Research; the Intramural Research Program of NHGRI, NIH; a Welch Foundation Grant (G-1495 to M. T. B.), an NIDA grant (DA025800 to M. T. B.) and a pilot project on grant P30ES007784 (to M. T. B.); and The German Research Foundation (SP1262/1-1 to A. S.). The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research and the Wellcome Trust. Funding for open access charge: NIH Roadmap for Medical Research, National Institutes of Health. NR 37 TC 30 Z9 30 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2010 VL 38 IS 2 AR e11 DI 10.1093/nar/gkp899 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 549XW UT WOS:000274088800005 PM 19897549 ER PT J AU Mejat, A Misteli, T AF Mejat, Alexandre Misteli, Tom TI LINC complexes in health and disease SO NUCLEUS-AUSTIN LA English DT Article DE LINC; lamins A/C; LMNA; SUN; nesprins; EDMD AB The cell nucleus communicates with the rest of the cell via nucleo/cytoplasmic transport of proteins and RNA through the nuclear pores. Direct mechanical links between the nucleus and the cytoplasm have recently emerged in the form of LINC (Linkers of the nucleoskeleton to the cytoskeleton) protein complexes. A LINC complex consists of four components. At its core are an inner nuclear membrane (INM) transmembrane protein and an outer nuclear membrane (ONM) transmembrane protein which physically interact with each other in the lumen of the NE. The INM LINC component interacts on the nucleoplasmic side with either the lamina or with an INM-associated protein. The ONM LINC component on the other hand contacts on the cytoplasmatic side a component of the cytoskeleton. This review highlights the components of LINC complexes and their emerging roles in mechanotransduction, nuclear migration, chromosome positioning, signaling, meiosis, cytoskeletal organization and human disease. C1 [Mejat, Alexandre; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Mejat, A (reprint author), Univ Lyon 1, Lab Biol Mol Cellule, Equipe Architecture Nucl & Differenciat Musculair, Ecole Normale Super Lyon,CNRS,UMR 5239, F-69365 Lyon, France. EM alexandre.mejat@ens-lyon.fr RI MEJAT, Alexandre/G-8635-2013 FU Intramural NIH HHS [ZIA BC010309-11] NR 140 TC 68 Z9 69 U1 0 U2 12 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1949-1034 J9 NUCLEUS-AUSTIN JI Nucleus-Austin PD JAN-FEB PY 2010 VL 1 IS 1 BP 40 EP 52 DI 10.4161/nucl.1.1.10530 PG 13 WC Cell Biology SC Cell Biology GA V28GB UT WOS:000208668200010 PM 21327104 ER PT J AU Gardner, D AF Gardner, Deborah TI Sensible Compromise: Will There Be Health Care Reform? SO NURSING ECONOMICS LA English DT Editorial Material AB Three significant challenges to the passage of health care legislation bear watching as they have the potential to make sensible compromise between the House and Senate unlikely. The first threat is the continuing exposure of the public to misinformation from media commentary and interest groups. If health care delivery issues weren't complex enough, another growing issue is the misuse of the filibuster, further obscuring change and clarity in legislative discussion. The third threat is a move by opponents of current health care reform to engage the Supreme Court and challenge the constitutionality of the legislation. If substantive health reform legislation fails to pass, nursing will have received a deep wound along with the rest of this country. Our voice as patient advocates must be stronger in these final days. C1 NIH, Off Org Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Gardner, D (reprint author), NIH, Off Org Dev, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD JAN-FEB PY 2010 VL 28 IS 1 BP 47 EP + PG 3 WC Nursing SC Nursing GA 554II UT WOS:000274428300008 PM 20306879 ER PT J AU Calzone, KA Cashion, A Feetham, S Jenkins, J Prows, CA Williams, JK Wung, SF AF Calzone, Kathleen A. Cashion, Ann Feetham, Suzanne Jenkins, Jean Prows, Cynthia A. Williams, Janet K. Wung, Shu-Fen TI Nurses transforming health care using genetics and genomics SO NURSING OUTLOOK LA English DT Article ID EGAPP WORKING GROUP; FUTURE; CANCER; RECOMMENDATIONS; INDIVIDUALS; STRATEGIES C1 [Calzone, Kathleen A.] Natl Canc Inst, NIH, Ctr Canc Res, Genet Branch, Bethesda, MD 20889 USA. [Cashion, Ann] Univ Tennessee, Ctr Hlth Sci, Acute & Chron Care Dept, Memphis, TN 38163 USA. [Feetham, Suzanne] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Jenkins, Jean] NHGRI, NIH, Bethesda, MD 20892 USA. [Prows, Cynthia A.] Childrens Hosp, Med Ctr, Div Patient Serv, Cincinnati, OH 45229 USA. [Prows, Cynthia A.] Childrens Hosp, Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. [Williams, Janet K.] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Wung, Shu-Fen] Univ Arizona, Coll Nursing, Tucson, AZ 85721 USA. RP Calzone, KA (reprint author), Natl Canc Inst, NIH, Ctr Canc Res, Genet Branch, 8901 Wisconsin Ave,Bldg 8,RM 5101, Bethesda, MD 20889 USA. EM calzonek@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 41 TC 42 Z9 45 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JAN-FEB PY 2010 VL 58 IS 1 BP 26 EP 35 DI 10.1016/j.outlook.2009.05.001 PG 10 WC Nursing SC Nursing GA 598XB UT WOS:000277871900011 PM 20113752 ER PT J AU Grady, PA AF Grady, Patricia A. TI Training new nurse scientists: Grants and opportunities available through the NINR SO NURSING OUTLOOK LA English DT Editorial Material C1 NINR, Off Sci Policy & Publ Liaison, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, Off Sci Policy & Publ Liaison, Bldg 31,Room 5B-10,31 Ctr Dr MSC 2178, Bethesda, MD 20892 USA. EM binghamr@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JAN-FEB PY 2010 VL 58 IS 1 BP 59 EP 61 DI 10.1016/j.outlook.2009.07.006 PG 3 WC Nursing SC Nursing GA 598XB UT WOS:000277871900015 PM 20113756 ER PT J AU Reynolds, MA Branch-Mays, GL Dawson, DR Novak, KF Ebersole, JL Novak, MJ Gunsolley, JC Holt, SC Mattison, JA Ingram, DK AF Reynolds, Mark A. Branch-Mays, Grishondra L. Dawson, Dolphus R. Novak, Karen F. Ebersole, Jeffrey L. Novak, M. John Gunsolley, John C. Holt, Stanley C. Mattison, Julie A. Ingram, Donald K. TI Differential sex effects of nutritional status on inflammatory periodontal disease in non-human primates Response SO NUTRITION LA English DT Letter C1 [Dawson, Dolphus R.; Novak, Karen F.; Ebersole, Jeffrey L.; Novak, M. John] Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Lexington, KY USA. [Gunsolley, John C.] Virginia Commonwealth Univ, Sch Dent, Richmond, VA USA. [Holt, Stanley C.] Forsyth Inst, Boston, MA USA. [Mattison, Julie A.] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. [Reynolds, Mark A.; Branch-Mays, Grishondra L.] Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA. RP Reynolds, MA (reprint author), Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JAN PY 2010 VL 26 IS 1 BP 140 EP 140 DI 10.1016/j.nut.2009.09.019 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 578XZ UT WOS:000276331800020 ER PT J AU Neuhouser, ML Nojomi, M Baumgartner, RN Baumgartner, KB Gilliland, F Bernstein, L Stanczyk, F Ballard-Barbash, R McTiernan, A AF Neuhouser, Marian L. Nojomi, Marzieh Baumgartner, Richard N. Baumgartner, Kathy B. Gilliland, Frank Bernstein, Leslie Stanczyk, Frank Ballard-Barbash, Rachel McTiernan, Anne TI Dietary Fat, Tamoxifen Use and Circulating Sex Hormones in Postmenopausal Breast Cancer Survivors SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID HIGH-CARBOHYDRATE DIET; RANDOMIZED-TRIAL; ATHYMIC MICE; PREMENOPAUSAL WOMEN; ESTROGEN METABOLISM; SERUM ESTROGEN; WEIGHT-GAIN; REDUCTION; HEALTH; RISK AB Evidence is inconsistent regarding whether dietary fat influences sex hormone concentrations. This issue is important for breast cancer survivors since clinical recommendations suggest maintaining low hormone levels primarily via pharmacologic agents. This study examines associations between dietary fat and circulating sex hormones among participants in the Health, Eating, Activity and Lifestyle (HEAL) Study, a cohort of breast cancer survivors (N = 511). During a postdiagnosis interview, detailed data were collected on diet, physical activity, lifestyle habits, and medication use (including tamoxifen). Staff measured height and weight and collected fasting bloods. Multivariate linear regression modeled associations of dietary fat with serum sex hormones. Among women using tamoxifen, we observed modest inverse associations of dietary fat with estrone (P 0.01), estradiol (P 0.05), testosterone (P 0.01), free testosterone (P 0.01), and DHEA (P 0.01) for higher vs. lower fat intake; but there was no evidence for a trend. Associations were consistent across measures (percent energy from fat, total, saturated, and polyunsaturated fat), and modest effect modification was observed between fat intake and tamoxifen in relation to hormones. Among women not using tamoxifen, fat intake was not associated with hormone concentrations. Further work is needed to confirm the findings and to understand the clinical implications of these observations. C1 [Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Nojomi, Marzieh] Iran Univ Med Sci, Tehran, Iran. [Baumgartner, Richard N.; Baumgartner, Kathy B.] Univ Louisville, Louisville, KY 40292 USA. [Gilliland, Frank; Bernstein, Leslie; Stanczyk, Frank] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Bernstein, Leslie] City Hope Canc Natl Med Ctr, Duarte, CA USA. [Ballard-Barbash, Rachel] NCI, Bethesda, MD 20892 USA. [McTiernan, Anne] Univ Washington, Seattle, WA 98195 USA. RP Neuhouser, ML (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4B402, Seattle, WA 98109 USA. EM mneuhous@fhcrc.org RI Nojomi, Marzieh/H-5694-2011 FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01PC-67010, N01-PC-35139, N01-PC-67007, N01-PC-35138, N01-PC-67009, N01-PC-35142]; National Institutes of Health [T32 CA09661, M01-RR-00037]; Contraceptive and Reproductive Experiences Study (CARE); National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528] FX Funding for this work was provided by National Cancer Institute contracts N01-CN-75036-20, N01-CN-05228, N01PC-67010/N01-PC-35139, N01-PC-67007/N01-PC-35138, and N01-PC-67009/N01-PC-35142 and National Institutes of Health training grant T32 CA09661. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by National Institutes of Health grant M01-RR-00037. Data collection for the Women's Contraceptive and Reproductive Experiences Study (CARE) at the University of Southern California was supported by the National Institute of Child Health and Human Development contract N01-HD-3-3175. Patient identification was supported in part by the California Department of Health Services grant 050Q-8709-S1528. NR 59 TC 1 Z9 1 U1 1 U2 3 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2010 VL 62 IS 2 BP 164 EP 174 AR PII 918786904 DI 10.1080/01635580903305359 PG 11 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 547FC UT WOS:000273870700004 PM 20099190 ER PT J AU Dunn, BK Richmond, ES Minasian, LM Ryan, AM Ford, LG AF Dunn, Barbara K. Richmond, Ellen S. Minasian, Lori M. Ryan, Anne M. Ford, Leslie G. TI A Nutrient Approach to Prostate Cancer Prevention: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SERUM ALPHA-TOCOPHEROL; SECONDARY END-POINTS; MANGANESE SUPEROXIDE-DISMUTASE; CLEAR STATISTICAL SIGNIFICANCE; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; KAPPA-B ACTIVATION; GAMMA-TOCOPHEROL; BETA-CAROTENE AB The Selenium and Vitamin E Cancer Prevention Trial (SELECT) randomized 35,533 healthy men, 55 yr old (50 yr if African American), with normal digital rectal exams and prostate specific antigens 4 ng/ml to 1) 200 g/day l-selenomethionine, 2) 400 IU/day all-rac-alpha-tocopheryl acetate (vitamin E), 3) both supplements, or 4) placebo for 7 to 12 yr. The hypotheses underlying SELECT, that selenium and vitamin E individually and together decrease prostate cancer incidence, derived from epidemiologic and laboratory evidence and significant secondary endpoints in the Nutritional Prevention of Cancer (selenium) and Alpha-Tocopherol Beta-Carotene (vitamin E) trials. In SELECT, prostate cancer incidence did not differ among the 4 arms: hazard ratios [99% confidence intervals (CIs)] for prostate cancer were 1.13 (99% CI = 0.95-1.35, P = 0.06; n = 473) for vitamin E, 1.04 (99% CI = 0.87-1.24, P = 0.62; n = 432) for selenium, and 1.05 (99% CI = 0.88-1.25, P = 0.52; n = 437) for selenium + vitamin E vs. 1.00 (n = 416) for placebo. Statistically nonsignificant increased risks of prostate cancer with vitamin E alone [relative risk (RR) = 1.13, P = 0.06) and newly diagnosed Type 2 diabetes mellitus with selenium alone (RR = 1.07, P = 0.16) were observed. SELECT data show that neither selenium nor vitamin E, alone or together, in the doses and formulations used, prevented prostate cancer in this heterogeneous population of healthy men. C1 [Dunn, Barbara K.; Richmond, Ellen S.; Minasian, Lori M.; Ryan, Anne M.; Ford, Leslie G.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Dunn, BK (reprint author), NCI, Canc Prevent Div, EPN 2056,6130 Execut Blvd, Bethesda, MD 20892 USA. EM dunnb@mail.nih.gov NR 152 TC 36 Z9 37 U1 0 U2 5 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2010 VL 62 IS 7 BP 896 EP 918 AR PII 927592864 DI 10.1080/01635581.2010.509833 PG 23 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 659QY UT WOS:000282583200007 PM 20924966 ER PT B AU Davis, CD Milner, JA AF Davis, Cindy D. Milner, John A. BE Wilson, T Temple, NJ Bray, GA Struble, MB TI Diet, Physical Activity, and Cancer Prevention SO NUTRITION GUIDE FOR PHYSICIANS SE Nutrition and Health Series LA English DT Article; Book Chapter DE Cancer; diet and prevention; body mass index; phytochemicals; meat; alcohol ID COLORECTAL-CANCER; BETA-CAROTENE; CARDIOVASCULAR-DISEASE; MEAT CONSUMPTION; UNITED-STATES; LUNG-CANCER; RED MEAT; RISK; POLYMORPHISMS; RESTRICTION AB Maintain a healthy weight throughout life: this is one of the most important ways to reduce cancer risk. A healthy weight can be promoted by limiting consumption of high-calorie foods and sugary drinks and by being physically active throughout life. Eat mostly foods of plant origin. This includes at least five portions/servings (at least 400 g or 14 oz) of a variety of vegetables and fruits everyday; eating whole grains and/or pulses (legumes) with every meal; and limiting refined starchy foods. Limit red meat intake to 60 g per week and limit processed meat consumption. Limit daily alcoholic drink consumption. Although there is no consumption that is not associated with an increased cancer risk, modest amounts of alcohol (two drinks a day for men or one drink a day for women) can protect against coronary heart disease. Limit consumption of salt-preserved or salty foods. Cancer survivors should follow the recommendations for cancer prevention regarding diet, healthy weight, and physical activity. C1 [Davis, Cindy D.; Milner, John A.] NCI, Canc Prevent Div, Rockville, MD USA. RP Davis, CD (reprint author), NCI, Canc Prevent Div, Rockville, MD USA. NR 34 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 978-1-60327-430-2 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 379 EP 393 DI 10.1007/978-1-60327-431-9_33 D2 10.1007/978-1-60327-431-9 PG 15 WC Geriatrics & Gerontology; Medicine, General & Internal; Nutrition & Dietetics SC Geriatrics & Gerontology; General & Internal Medicine; Nutrition & Dietetics GA BMR61 UT WOS:000273401400033 ER PT J AU Cheng, CY Lee, KE Duggal, P Moore, EL Wilson, AF Klein, R Bailey-Wilson, JE Klein, BEK AF Cheng, Ching-Yu Lee, Kristine E. Duggal, Priya Moore, Emily L. Wilson, Alexander F. Klein, Ronald Bailey-Wilson, Joan E. Klein, Barbara E. K. TI Genome-wide Linkage Analysis of Multiple Metabolic Factors: Evidence of Genetic Heterogeneity SO OBESITY LA English DT Article ID BEAVER DAM EYE; INSULIN-RESISTANCE SYNDROME; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; NATIONAL-HEART; FAMILY-HISTORY; URIC-ACID; HYPERTENSION; COMPONENTS; SCAN AB The metabolic syndrome is a highly complex disease and has become one of the major public-health challenges worldwide. We sought to identify genetic loci with potential influence on multiple metabolic factors in a white population in Beaver Dam, Wisconsin, and to explore the possibility of genetic heterogeneity by family history of diabetes (FHD). Three metabolic factors were generated using principal-component factor analysis, and they represented: (i) glycemia, (ii) blood pressure, and (iii) combined (BMI, high-density lipoprotein (HDL) cholesterol, and serum uric acid) factors. Multipoint model-free linkage analysis of these factors with 385 microsatellite markers was performed on 1,055 sib-pairs, using Haseman-Elston regression. Genome-wide suggestive evidence of linkage was found at 30 cM on chromosome 22q (empirical P (P(e)) = 0.0002) for the glycemia factor, at 188-191 cM on chromosome 1q (P(e) = 0.0007) for the blood pressure factor, and at 82 cM on chromosome 17q (P(e) = 0.0007) for the combined factor. Subset analyses of the families by FHD showed evidence of genetic heterogeneity, with divergent linkage signals in the subsets on at least four chromosomes. We found evidence of genetic heterogeneity by FHD for the three metabolic factors. The results also confirmed findings of previous studies that mapped components of the metabolic syndrome to a chromosome 1q region. C1 [Lee, Kristine E.; Moore, Emily L.; Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Cheng, Ching-Yu; Duggal, Priya; Wilson, Alexander F.; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Cheng, Ching-Yu; Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Cheng, Ching-Yu] Natl Yang Ming Univ, Dept Ophthalmol, Sch Med, Taipei 112, Taiwan. [Cheng, Ching-Yu] Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei, Taiwan. RP Klein, BEK (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM kleinb@epi.ophth.wisc.edu RI Wilson, Alexander/C-2320-2009; Cheng, Ching-Yu/K-7017-2013; OI Cheng, Ching-Yu/0000-0003-0655-885X; Bailey-Wilson, Joan/0000-0002-9153-2920; Klein, Ronald/0000-0002-4428-6237 FU National Institutes of Health [EY06594, EY015286]; National Human Genome Research Institute, National Institutes of Health; National Center for Research Resources [RR03655] FX This study was supported by National Institutes of Health Grants EY06594 (to R. K. and B. E. K. K.) and EY015286 (to B. E. K. K.), Research to Prevent Blindness Senior Investigator Awards (to R. K. and B. E. K. K.), and in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Some of the results of this article were obtained by using the program package SAGE, which is supported by a US Public Health Service Resource Grant (RR03655) from the National Center for Research Resources. We thank W. H. Linda Kao, PhD (Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD) for her invaluable suggestions. NR 41 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD JAN PY 2010 VL 18 IS 1 BP 146 EP 152 DI 10.1038/oby.2009.142 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 538UU UT WOS:000273210400021 PM 19444228 ER PT J AU Rausch, ME Legro, RS Barnhart, HX Schlaff, WD Carr, BR Diamond, MP Carson, SA Steinkampf, MP McGovern, PG Cataldo, NA Gosman, GG Nestler, JE Giudice, LC Leppert, PC Myers, ER Coutifaris, C AF Rausch, Mary E. Legro, Richard S. Barnhart, Huiman X. Schlaff, William D. Carr, Bruce R. Diamond, Michael P. Carson, Sandra A. Steinkampf, Michael P. McGovern, Peter G. Cataldo, Nicholas A. Gosman, Gabriella G. Nestler, John E. Giudice, Linda C. Leppert, Phyllis C. Myers, Evan R. Coutifaris, Christos CA Reprod Med Network TI Predictors of Pregnancy in Women With Polycystic Ovary Syndrome COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Two professional medical societies used expert opinion as the basis for their recommendation that current first-line treatment of polycystic ovary syndrome (PCOS)-related infertility should be ovulation induction with the selective estrogen receptor modulator, clomiphene citrate (CC), for up to 6 ovulatory cycles, with the addition of the insulin sensitizer metformin only for glucose intolerance. This prospective, multicenter, randomized clinical trial was designed to determine which baseline patient characteristics among women with PCOS were predictive of success of fertility treatment in 4 clinically relevant prognostic models of ovulation, conception, pregnancy, and live birth. Live birth was the primary study outcome. Between 2002 and 2004, ovulation was induced in 626 infertile women with PCOS by either CC plus placebo (n = 209), metformin plus placebo (n = 208), or combination CC plus metformin (n = 209). The factors that were significant for prediction of treatment success in all 4 conception models were body mass index, baseline free androgen index, proinsulin level, and duration of attempting conception. History of a prior pregnancy loss was predictive of treatment success in the models for ovulation and conception, but was not predictive of pregnancy or live birth. A low hirsutism score (<8) was not predictive of ovulation success, but was predictive of conception, pregnancy, and live birth. Age had divergent effects on ovulation and pregnancy outcomes. Age 34 or younger was a predictive factor for a successful pregnancy and live birth, whereas age greater than 34 years was predictive only of successful ovulation. Smoking history was not a significant predictor. These findings may be useful to counsel women with PCOS on their likelihood for live birth and to select infertility therapy. C1 [Rausch, Mary E.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Colorado, Denver, CO 80202 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Alabama, Birmingham, AL USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Pittsburgh, Pittsburgh, PA USA. Virginia Commonwealth Univ, Dept Med, Sch Med, Richmond, VA 23298 USA. Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA. NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. RP Rausch, ME (reprint author), Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD JAN PY 2010 VL 65 IS 1 BP 30 EP 32 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 541OA UT WOS:000273424100017 ER PT J AU Silver, RM Zhao, Y Spong, CY Sibai, B Wendel, G Wenstrom, K Samuels, P Caritis, SN Sorokin, Y Miodovnik, M O'Sullivan, MJ Conway, D Wapner, RJ AF Silver, Robert M. Zhao, Yuan Spong, Catherine Y. Sibai, Baha Wendel, George, Jr. Wenstrom, Katharine Samuels, Philip Caritis, Steve N. Sorokin, Yoram Miodovnik, Menachem O'Sullivan, Mary J. Conway, Deborah Wapner, Ronald J. CA Eunice Kennedy Shriver Natl Inst TI Prothrombin Gene G20210A Mutation and Obstetric Complications SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FACTOR-V-LEIDEN; INTRAUTERINE GROWTH RESTRICTION; LATE FETAL LOSS; PREGNANCY COMPLICATIONS; INHERITED THROMBOPHILIA; RECURRENT MISCARRIAGE; RISK-FACTORS; WOMEN; PREVALENCE; OUTCOMES AB OBJECTIVE: To estimate whether maternal carriage of the prothrombin gene G20210A mutation is associated with pregnancy loss, preeclampsia, placental abruption, or small for gestational age (SGA) neonates in a low-risk, prospective cohort. METHODS: This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development factor V Leiden study, a multicenter, prospective, observational cohort of 5,188 unselected singleton gestations. A total of 4,167 first-trimester samples were available for analysis and were tested for the prothrombin G20210A mutation. Obstetric complications were compared between women with and without the prothrombin G20210A mutation by univariable and multivariable analysis. RESULTS: A total of 157 (3.8%) women had the prothrombin gene mutation (156 heterozygous and one homozygous). Carriers of the prothrombin G20210A mutation had similar rates of pregnancy loss, preeclampsia, SGA neonates, and abruption compared with noncarriers. Results were similar in a multivariable analysis controlling for age, race, prior pregnancy loss, prior SGA neonates, and family history of thromboembolism. Three thromboembolic events occurred in women testing negative for the mutation. CONCLUSION: There was no association between the prothrombin G20210A mutation and pregnancy loss, preeclampsia, abruption, or SGA neonates in a low-risk, prospective cohort. These data raise questions about the practice of screening women without a history of thrombosis or adverse pregnancy outcomes for this mutation. (Obstetric Gynecol 2010;175:14-20) C1 Univ Alabama, Dept Obstet, Birmingham, AL USA. Univ Alabama, Dept Gynecol, Birmingham, AL USA. Univ Chicago, Chicago, IL 60637 USA. Univ Cincinnati, Cincinnati, OH USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Miami, Miami, FL USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Tennessee, Memphis, TN USA. Univ Texas San Antonio, San Antonio, TX USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Silver, Robert M.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Wayne State Univ, Detroit, MI USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Silver, RM (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, 30 North 1900 East,Room 2B308, Salt Lake City, UT 84132 USA. EM bsilver@hsc.utah.edu RI Samuels, Philip/E-4011-2011; OI caritis, steve/0000-0002-2169-0712 FU NCATS NIH HHS [UL1 TR000005]; NICHD NIH HHS [HD27915, HD21410, HD21414, HD27860, HD27861, HD27869, HD27917, HD34116, HD34136, HD34208, HD34210, HD36801, U01 HD036801, U10 HD021410, U10 HD027860, U10 HD027869, U10 HD027905, U10 HD027915, U10 HD027917, U10 HD034116, U10 HD034122, U10 HD034136, U10 HD034208, U10 HD034208-11, U10 HD036801, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208] NR 33 TC 52 Z9 56 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2010 VL 115 IS 1 BP 14 EP 20 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 540FU UT WOS:000273317500003 PM 20027028 ER PT J AU Heck, JE Charbotel, B Moore, LE Karami, S Zaridze, DG Matveev, V Janout, V Kollarova, H Foretova, L Bencko, V Szeszenia-Dabrowska, N Lissowska, J Mates, D Ferro, G Chow, WH Rothman, N Stewart, P Brennan, P Boffetta, P AF Heck, J. E. Charbotel, B. Moore, L. E. Karami, S. Zaridze, D. G. Matveev, V. Janout, V. Kollarova, H. Foretova, L. Bencko, V. Szeszenia-Dabrowska, N. Lissowska, J. Mates, D. Ferro, G. Chow, W-H Rothman, N. Stewart, P. Brennan, P. Boffetta, P. TI Occupation and renal cell cancer in Central and Eastern Europe SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID DRY CLEANING WORKERS; RISK-FACTORS; KIDNEY CANCER; CARCINOMA; MORTALITY; EXPOSURE; GERMANY; LAUNDRY; BLADDER; SWEDEN AB Objective: Central and Eastern Europe has among the highest rates of renal cell cancer worldwide. Few studies have been conducted in these areas to investigate the possible role of occupational exposures in renal cell cancer aetiology. The purpose of this study was to examine the association of renal cell cancer with employment in specific occupations and industries. Methods: From 1999 to 2003, we conducted a hospital-based case-control study in seven areas of the Czech Republic, Poland, Romania and Russia. A detailed occupational history was collected from renal cell cancer cases and controls, together with information on potential confounders. Odds ratios (ORs) and 95% CI of cancer risk were calculated for having ever been employed in selected jobs and industries, with follow-up analyses examining duration of employment. Results: A total of 992 histologically confirmed incident renal cell cancer cases and 1459 controls were included in the analysis. An increased risk of renal cell cancer was observed for workers in agricultural labour and animal husbandry (OR 1.43; 95% CI 1.05 to 1.93), particularly among women employed as general farm workers (OR 2.73; 95% CI 1.05 to 7.13). Risk gradients for agricultural work increased with longer employment. An overall increased risk of renal cell cancer was seen among architects and engineers (OR 1.89; 95% CI 1.35 to 2.65), and mechanical engineers (OR 1.71; 95% CI 1.03 to 2.84). Conclusions: Our data suggest an association between renal cell cancer and agricultural work, particularly among female workers. C1 [Heck, J. E.; Charbotel, B.; Ferro, G.; Brennan, P.; Boffetta, P.] Int Agcy Res Canc, F-69372 Lyon, France. [Heck, J. E.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Heck, J. E.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Charbotel, B.] Univ Lyon 1, UMRESTTE, F-69365 Lyon, France. [Moore, L. E.; Karami, S.; Chow, W-H; Rothman, N.; Stewart, P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zaridze, D. G.] Russian NN Blokhin Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Matveev, V.] Russian NN Blokhin Canc Res Ctr, Dept Oncourol, Moscow, Russia. [Janout, V.; Kollarova, H.] Palacky Univ, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Foretova, L.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Bencko, V.] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, CR-11636 Prague 1, Czech Republic. [Szeszenia-Dabrowska, N.] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Lissowska, J.] Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, J.] Maria Sklodowska Curie Inst Oncol, Warsaw, Poland. [Mates, D.] Inst Publ Hlth, Bucharest, Romania. [Stewart, P.] Stewart Exposure Assessments LLC, Arlington, VA USA. [Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. RP Boffetta, P (reprint author), Int Prevent Res Inst, 95 Cours Lafayette, F-69006 Lyon, France. EM boffetta@iarc.fr RI Zaridze, David/K-5605-2013; Heck, Julia/B-5230-2009; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI Heck, Julia/0000-0001-8713-8413; mates, dana/0000-0002-6219-9807; Lissowska, Jolanta/0000-0003-2695-5799 FU NIH; National Cancer Institute; Division of Cancer Epidemiology and Genetics FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 42 TC 5 Z9 6 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JAN PY 2010 VL 67 IS 1 BP 47 EP 53 DI 10.1136/oem.2009.046250 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 535TR UT WOS:000272994700008 PM 19737732 ER PT B AU Havlik, RJ AF Havlik, Richard J. BE Brennan, M Karpiak, SE Shippy, RA Cantor, MH TI HEALTH STATUS, COMORBIDITIES, AND HEALTH-RELATED QUALITY-OF-LIFE SO OLDER ADULTS WITH HIV: AN IN-DEPTH EXAMINATION OF AN EMERGING POPULATION SE HIV AIDS-Medical Social and Psychological Aspects LA English DT Article; Book Chapter ID HIV-INFECTION; ANTIRETROVIRAL TREATMENT; THERAPY; IMPACT C1 [Havlik, Richard J.] NIA, NIH, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Havlik, Richard J.] NHLBI, Bethesda, MD USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-054-1 J9 HIV AIDS-MED SOC PSY PY 2010 BP 13 EP 25 PG 13 WC Gerontology; Public, Environmental & Occupational Health SC Geriatrics & Gerontology; Public, Environmental & Occupational Health GA BQO41 UT WOS:000281447100002 ER PT S AU King, RB AF King, Rosalind Berkowitz BE Woodruff, TK Zoloth, L CampoEngelstein, L Rodriguez, S TI Perspectives on Oncofertility from Demography and Economics SO ONCOFERTILITY: ETHICAL, LEGAL , SOCIAL, AND MEDICAL PERSPECTIVES SE Cancer Treatment and Research LA English DT Article; Book Chapter ID TIME; FERTILITY; CHILDREN; IMPACT C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Demog & Behav Sci Branch, Bethesda, MD USA. RP King, RB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Demog & Behav Sci Branch, Bethesda, MD USA. EM rozking@mail.nih.gov FU NICHD NIH HHS [5RL1HD058296, RL1 HD058296-03, RL1 HD058296]; NIDCR NIH HHS [8UL1DE019587, UL1 DE019587-03, UL1 DE019587] NR 21 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-1-4419-6517-2 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2010 VL 156 BP 371 EP 379 DI 10.1007/978-1-4419-6518-9_28 D2 10.1007/978-1-4419-6518-9 PG 9 WC Oncology; Reproductive Biology SC Oncology; Reproductive Biology GA BQX48 UT WOS:000282063100028 PM 20811848 ER PT J AU Coleman, CN Glatstein, E AF Coleman, C. Norman Glatstein, Eli TI The Road Not Taken and Choices in Radiation Oncology SO ONCOLOGIST LA English DT Article; Proceedings Paper CT Conference on New Paradigms in Radiation Oncology CY OCT 31-NOV 01, 2008 CL Univ Pennsylvania, Philadelphia, PA HO Univ Pennsylvania DE Radiation oncology; Personalized medicine; Medical ethics; Medical technology ID RANDOMIZED CLINICAL-TRIALS; CANCER; HEALTH AB Accomplishments and contributions in a career in radiation oncology, and in medicine in general, involve individual choices that impact the direction of a specialty, decisions in patient care, consequences of treatment outcome, and personal satisfaction. Issues in radiation oncology include: the development and implementation of new radiation treatment technology; the use of multimodality and biologically based therapies; the role of nonradiation "energy" technologies, often by other medical specialties, including the need for quality assurance in treatment and data reporting; and the type of evidence, including appropriate study design, analysis, and rigorous long-term follow-up, that is sought before widespread implementation of a new treatment. Personal choices must weigh: the pressure from institutions-practices, departments, universities, and hospitals; the need to serve society and the underserved; the balance between individual reward and a greater mission; and the critical role of personal values and integrity, often requiring difficult and "life-defining" decisions. The impact that each of us makes in a career is perhaps more a result of character than of the specific details enumerated on one's curriculum vitae. The individual tapestry weaved by choosing the more or less traveled paths during a career results in many pathways that would be called success; however, the one path for which there is no good alternative is that of living and acting with integrity. The Oncologist 2010; 15: 332-337 C1 [Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Glatstein, Eli] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM ccoleman@mail.nih.gov NR 13 TC 1 Z9 1 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2010 VL 15 IS 4 BP 332 EP 337 DI 10.1634/theoncologist.2009-S102 PG 6 WC Oncology SC Oncology GA 587AD UT WOS:000276957400002 PM 20413638 ER PT J AU Citrin, D Cotrim, AP Hyodo, F Baum, BJ Krishna, MC Mitchell, JB AF Citrin, Deborah Cotrim, Ana P. Hyodo, Fuminori Baum, Bruce J. Krishna, Murali C. Mitchell, James B. TI Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury SO ONCOLOGIST LA English DT Article DE Radioprotector; Mitigators; Amifostine; Tempol ID ANGIOTENSIN-CONVERTING ENZYME; KERATINOCYTE GROWTH-FACTOR; SENSITIVE CONTRAST AGENTS; COLONY-STIMULATING FACTOR; TOLL-LIKE RECEPTOR-5; NECK-CANCER PATIENTS; SUPEROXIDE-DISMUTASE; RANDOMIZED-TRIAL; INDUCED FIBROSIS; IRRADIATED MICE AB Radiation is used in the treatment of a broad range of malignancies. Exposure of normal tissue to radiation may result in both acute and chronic toxicities that can result in an inability to deliver the intended therapy, a range of symptoms, and a decrease in quality of life. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present be-fore or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. Herein, we review agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury. Few agents are approved for clinical use, but many new compounds show promising results in preclinical testing. The Oncologist 2010; 15: 360-371 C1 [Citrin, Deborah] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hyodo, Fuminori; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cotrim, Ana P.; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. RP Citrin, D (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, CRC B2-3500, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; Division of Intramural Research, National Institute of Dental and Craniofacial Research FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and the Division of Intramural Research, National Institute of Dental and Craniofacial Research. NR 91 TC 147 Z9 157 U1 4 U2 11 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2010 VL 15 IS 4 BP 360 EP 371 DI 10.1634/theoncologist.2009-S104 PG 12 WC Oncology SC Oncology GA 587AD UT WOS:000276957400005 PM 20413641 ER PT J AU Citrin, D Camphausen, K Wood, BJ Quezado, M Denobile, J Pingpank, JF Royal, RE Alexander, HR Seidel, G Steinberg, SM Shuttack, Y Libutti, SK AF Citrin, Deborah Camphausen, Kevin Wood, Bradford J. Quezado, Martha Denobile, John Pingpank, James F. Royal, Richard E. Alexander, H. Richard Seidel, Geoffrey Steinberg, Seth M. Shuttack, Yvonne Libutti, Steven K. TI A Pilot Feasibility Study of TNFerade (TM) Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer SO ONCOLOGY LA English DT Article DE Rectal carcinoma; Radiation; Neoadjuvant; TNFerade (TM) ID POSTOPERATIVE ADJUVANT CHEMOTHERAPY; PREOPERATIVE CHEMORADIOTHERAPY; PANCREATIC-CANCER; TUMOR-REGRESSION; RANDOMIZED-TRIAL; PHASE-II; RADIOTHERAPY; CARCINOMA; SURVIVAL; CHEMORADIATION AB Objective: The purpose of this pilot study was to evaluate the feasibility and tolerability of weekly intratumoral TNFerade (TM) injections combined with concurrent capecitabine and radiotherapy in the treatment of patients with locally advanced rectal cancer. Methods: Patients with T3, T4, or N+ rectal cancer received radiotherapy to a total dose of 50.4-54 Gy in combination with capecitabine 937.5 mg/m(2) p.o. b.i.d. TNFerade (TM) at a dose of 4 x 10(10) particle units was injected into the rectal tumor on the first day of radiotherapy and weekly for a total of 5 injections. Surgery was performed 5-10 weeks after the completion of chemoradiation. Results: Nine patients were enrolled in this pilot trial. The stage was cT2 in 2 patients, cT3 in 6 patients, cT4 in 1 patient, N- in 7 patients and N+ in 2 patients. Eight patients completed all treatments. Grade 3 hematologic toxicity was observed in 2 patients. There was no toxicity directly attributable to the injection procedure. A complete pathologic response was observed in 2 of 9 patients. Conclusions: This study demonstrates the feasibility of weekly intratumoral TNFerade (TM) injections during chemoradiotherapy for locally advanced rectal cancer. Pathologic responses with this combination compare favorably to published rates. Copyright (C) 2011 S. Karger AG, Basel C1 [Citrin, Deborah] NCI, Sect Translat Radiat Oncol, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.] NHLBI, Ctr Intervent Oncol, NIH, Ctr Clin,NCI, Bethesda, MD 20892 USA. [Quezado, Martha] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Denobile, John] Natl Naval Med Ctr, Dept Surg, Bethesda, MD USA. [Pingpank, James F.; Royal, Richard E.; Libutti, Steven K.] NIH, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Alexander, H. Richard] Univ Maryland, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21201 USA. [Alexander, H. Richard] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Seidel, Geoffrey; Shuttack, Yvonne] SAIC Frederick, Clin Monitoring Res Program, Frederick, MD USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Libutti, Steven K.] Montefiore Med Ctr, Albert Einstein Coll Med, Montefiore Einstein Ctr Canc Care, Bronx, NY 10467 USA. RP Citrin, D (reprint author), NCI, Sect Translat Radiat Oncol, Radiat Oncol Branch, Ctr Canc Res,NIH, 10 CRC B2-3500,10 Ctr Dr, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov FU NCI; Clinical Center, NIH; National Cancer Institutes of Health [HH-SN261200800001E] FX This research was supported in part by the Intramural Research Program of NCI and Clinical Center, NIH.; This project was funded in part with federal funds from the National Cancer Institutes of Health under contract HH-SN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 29 TC 12 Z9 12 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2010 VL 79 IS 5-6 BP 382 EP 388 DI 10.1159/000323488 PG 7 WC Oncology SC Oncology GA 761EB UT WOS:000290377100011 PM 21447969 ER PT B AU Chau, CH Figg, WD AF Chau, Cindy H. Figg, William Douglas BE Kelly, WK Halabi, S TI Preclinical Drug Assessment SO ONCOLOGY CLINICAL TRIALS LA English DT Article; Book Chapter ID EARLY CLINICAL-TRIALS; TUMOR-CELL-LINES; IN-VITRO; ORTHOTOPIC MODELS; TOPOISOMERASE-II; GENE-EXPRESSION; CANCER; SCREEN; MICE; TECHNOLOGIES C1 [Chau, Cindy H.; Figg, William Douglas] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Chau, CH (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 28 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-38-9 PY 2010 BP 21 EP 27 PG 7 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BMU36 UT WOS:000273577900004 ER PT B AU Kurkjian, C Chen, HX AF Kurkjian, Carla Chen, Helen X. BE Kelly, WK Halabi, S TI Reporting of Adverse Events SO ONCOLOGY CLINICAL TRIALS LA English DT Article; Book Chapter C1 [Kurkjian, Carla] Univ Oklahoma, Hlth Sci Ctr, Dept Internal Med, Hematol Oncol Sect, Oklahoma City, OK USA. [Chen, Helen X.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Kurkjian, C (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Internal Med, Hematol Oncol Sect, Oklahoma City, OK USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-38-9 PY 2010 BP 141 EP 149 PG 9 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BMU36 UT WOS:000273577900017 ER PT B AU Korn, EL Freidlin, B AF Korn, Edward L. Freidlin, Boris BE Kelly, WK Halabi, S TI Interim Analysis of Phase III Trials SO ONCOLOGY CLINICAL TRIALS LA English DT Article; Book Chapter ID DATA-MONITORING COMMITTEES; RANDOMIZED CLINICAL-TRIALS; SOUTHWEST-ONCOLOGY-GROUP; CELL LUNG-CANCER; INTRAARTERIAL IODINE-131-LABELED LIPIODOL; RESECTABLE HEPATOCELLULAR-CARCINOMA; SURGICAL ADJUVANT BREAST; RISK CERVICAL-CANCER; EARLY STOPPING RULES; OVARIAN-CANCER C1 [Korn, Edward L.; Freidlin, Boris] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 76 TC 2 Z9 2 U1 1 U2 2 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-38-9 PY 2010 BP 163 EP 177 PG 15 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BMU36 UT WOS:000273577900019 ER PT B AU Simon, R AF Simon, Richard BE Kelly, WK Halabi, S TI Use of Genomics in Therapeutic Clinical Trials SO ONCOLOGY CLINICAL TRIALS LA English DT Article; Book Chapter ID METASTATIC BREAST-CANCER; DNA MICROARRAY DATA; GENE-EXPRESSION; PHASE-II; PHARMACOGENOMIC PREDICTOR; DRUG DEVELOPMENT; TUMOR-MARKERS; END-POINTS; DESIGN; CHEMOTHERAPY C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-38-9 PY 2010 BP 227 EP 238 PG 12 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BMU36 UT WOS:000273577900024 ER PT B AU Grady, C AF Grady, Christine BE Kelly, WK Halabi, S TI Writing a Consent Form SO ONCOLOGY CLINICAL TRIALS LA English DT Article; Book Chapter ID INFORMED-CONSENT; CLINICAL-TRIALS; DOCUMENTS; QUALITY C1 NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-38-9 PY 2010 BP 327 EP 333 PG 7 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BMU36 UT WOS:000273577900035 ER PT B AU Trimble, EL Martin, A AF Trimble, Edward L. Martin, Alison BE Kelly, WK Halabi, S TI How Cooperative Groups Function SO ONCOLOGY CLINICAL TRIALS LA English DT Article; Book Chapter C1 [Trimble, Edward L.] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Martin, Alison] Melanoma Res Alliance, Washington, DC USA. RP Trimble, EL (reprint author), NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-38-9 PY 2010 BP 335 EP 342 PG 8 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BMU36 UT WOS:000273577900036 ER PT J AU Roschewski, M Wilson, WH AF Roschewski, Mark Wilson, Wyndham H. TI Biology and Management of Rare Primary Extranodal T-cell Lymphomas SO ONCOLOGY-NEW YORK LA English DT Article ID GAMMA-DELTA; CLINICOPATHOLOGICAL ENTITY; CELIAC-DISEASE; PROGNOSTIC-FACTORS; CLINICAL-OUTCOMES; FEATURES; TRANSPLANTATION; CLASSIFICATION AB Peripheral T-cell lymphomas (PTCLs) are uncommonly encountered malignancies in the United States, and hepatosplenic T-cell lymphoma (HSTCL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and enteropathy-type T-cell lymphoma (ETTCL) are rare subtypes of PTCLs that often present with primarily extranodal disease. Despite the fact that these tumors have distinct clinical and pathologic features, they are often diagnosed after significant delay. The combination of delay in diagnosis with ineffective therapies has resulted in a poor prognosis in most cases. Techniques that identify T-cell receptor gene rearrangements and flow cytometry that can identify characteristic immunophenotypes have guided our understanding of the underlying cell of origin of these rare PTCLs. As knowledge regarding the biology of these lymphomas increases alongside the development of newer therapeutics with novel mechanisms, clinicians must accordingly improve their familiarity with the clinical settings in which these rare malignancies arise as well as the pathologic features that make them unique C1 [Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Roschewski, Mark] Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Wilson, WH (reprint author), NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 10,Room 4N115, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 36 TC 4 Z9 4 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2010 VL 24 IS 1 BP 94 EP 100 PG 7 WC Oncology SC Oncology GA 800AZ UT WOS:000293330700011 PM 20187328 ER PT J AU Su, LY Xu, GH Shen, J Tuo, Y Zhang, XG Jia, SQ Chen, Z Su, XL AF Su, Liya Xu, Guihua Shen, Jie Tuo, Ya Zhang, Xingguang Jia, Shuqin Chen, Zhong Su, Xiulan TI Anticancer bioactive peptide suppresses human gastric cancer growth through modulation of apoptosis and the cell cycle SO ONCOLOGY REPORTS LA English DT Article DE bioactive peptide; gastric cancer; tumor growth; apoptosis; cell cycle ID C-MYC; STEM-CELLS; EXPRESSION; BCL-2; CARCINOGENESIS; CARCINOMAS; MEMBRANE; THERAPY; MARKERS; BAX AB Anticancer bioactive peptide (ACBP) was extracted from goat spleens with immunization by human gastric cancer extracts. ACBP was biochemically purified and identified as similar to 8,000 Da peptide. Here we report that ACBP significantly inhibited the growth of human gastric cancer line BGC-823 in vitro in a dose-dependent manner. ACBP induced BGC-823 cell apoptosis was observed morphologically both by light microscopy and electronic microscopy; and ACBP-induced apoptosis and G(0)/G(1) cell cycle arrest were quantified by Annexin V-FITC/PI staining and flow cytometry. At the molecular level, ACBP induced p16(Ink4), p21(Waf1), p27(Kipl), and bax tumor suppressor and apoptotic gene expression, as well as inhibited cyclin D1, c-myc, and bcl-2 gene expression that promote tumorigenesis. In vivo, ACBP dramatically inhibited human gastric tumor growth in a xenograft model with no apparent cytotoxicity to host. Our study suggests that ACBP could be a powerful anticancer biological product through induction of cell apoptosis and cell cycle arrest. C1 [Su, Liya; Su, Xiulan] Capital Med Univ, Dept Cell Biol, Beijing, Peoples R China. [Su, Liya; Xu, Guihua; Shen, Jie; Jia, Shuqin; Su, Xiulan] Inner Mongolia Med Coll, Clin Med Res Ctr, Hohhot, Inner Mongolia, Peoples R China. [Tuo, Ya] Inner Mongolia Med Coll, Dept Prevent Med, Hohhot, Inner Mongolia, Peoples R China. [Zhang, Xingguang] Affiliated Hosp, Inner Mongolia Med Coll, Lab Testing Ctr, Hohhot, Inner Mongolia, Peoples R China. [Chen, Zhong] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Su, XL (reprint author), Huhhot 1 Tongdao N St, Hohhot 010050, Inner Mongolia, Peoples R China. EM chenz@nidcd.nih.gov; xlsu@hotmail.com FU National Natural Science Foundation of China [30860327]; Major Project of Inner Mongolia Medical College, China [ZD9809]; NIH/NIDCD, USA [Z01-DC-000016] FX This study was supported by the National Natural Science Foundation of China (No. 30860327, China), Major Project of Inner Mongolia Medical College (No. ZD9809, China), and NIH/NIDCD intramural research projects Z01-DC-000016 (USA). We thank Dr Ke Yang (Beijing University Medical Health Center) for helpful discussions and for providing cells lines. We also thank Cindy Clark (NIH library) for helpful revision of the manuscript. NR 29 TC 13 Z9 15 U1 0 U2 4 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JAN PY 2010 VL 23 IS 1 BP 3 EP 9 DI 10.3892/or_00000599 PG 7 WC Oncology SC Oncology GA 550ND UT WOS:000274133800001 PM 19956858 ER PT J AU Moustakas, A Kreisl, TN AF Moustakas, Argirios Kreisl, Teri N. TI New treatment options in the management of glioblastoma multiforme: a focus on bevacizumab SO ONCOTARGETS AND THERAPY LA English DT Review DE glioblastoma multiforme; angiogenesis; bevacizumab ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; RECURRENT MALIGNANT GLIOMA; METASTATIC COLORECTAL-CANCER; HIGH-GRADE GLIOMA; PROGRESSION-FREE SURVIVAL; INHIBITS TUMOR-GROWTH; ANTI-VEGF ANTIBODY; PLUS IRINOTECAN; RADIATION-THERAPY AB Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults and carries the poorest prognosis. Despite recent progress in molecular biology, neuro-imaging and neuro-surgical care, the management of patients with GBM continues to harbor significant challenges. Survival after diagnosis is poor even with the most aggressive approach using multimodality therapy. Although the etiology of malignant gliomas is not known, the dependency of tumor growth on angiogenesis has identified this pathway as a promising therapeutic target. Bevacizumab was the first antiangiogenic therapy approved for use in cancer and received accelerated Food and Drug Administration approval for the treatment of recurrent GBM in 2009, the first new drug for this disease in over a decade. This review describes the rationale behind the treatment of GBM with bevacizumab. The pharmacology, efficacy, safety and tolerability of bevacizumab will also be reviewed. C1 [Moustakas, Argirios; Kreisl, Teri N.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Kreisl, TN (reprint author), NCI, Neurooncol Branch, NIH, 9030 Old Georgetown Rd,Bloch Bldg 82, Bethesda, MD 20892 USA. EM kreislt@mail.nih.gov NR 120 TC 10 Z9 10 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-6930 J9 ONCOTARGETS THER PY 2010 VL 3 BP 27 EP 38 PG 12 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 712MB UT WOS:000286669800001 PM 20616955 ER PT S AU Chernomordik, V Hassan, M Lee, SB Zielinski, R Capala, J Gandjbakhche, A AF Chernomordik, Victor Hassan, Moinuddin Lee, Sang Bong Zielinski, Rafal Capala, Jacek Gandjbakhche, Amir BE Alfano, RR TI Application of NIR fluorescent markers to quantify expression level of HER2 receptors in carcinomas in vivo SO OPTICAL BIOPSY VII SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Optical Biopsy VII CY JAN 25-28, 2010 CL San Francisco, CA SP SPIE, Ocean Optics Inc DE Medical and biological imaging; Spectroscopy and; fluorescence; Clinical applications; HER2 overexpression ID TUMORS; CANCER AB HER2 overexpression has been associated with a poor prognosis and resistance to therapy in breast cancer patients. However, quantitative estimates of this important characteristic have been limited to ex vivo ELISA essays of tissue biopsies and/or PET. We develop a novel approach in optical imaging, involving specific probes, not interfering with the binding of the therapeutic agents, thus, excluding competition between therapy and imaging. Affibody-based molecular probes seem to be ideal for in vivo analysis of HER2 receptors using near-infrared optical imaging. Fluorescence intensity distributions, originating from specific markers in the tumor area, can reveal the corresponding fluorophore concentration. We use temporal changes of the signal from a contrast agent, conjugated with HER2-specific Affibody as a signature to monitor in vivo the receptors status in mice with different HER2 over-expressed tumor models. Kinetic model, incorporating saturation of the bound ligands in the tumor area due to HER2 receptor concentration, is suggested to analyze relationship between tumor cell characteristics, i.e., HER2 overexpression, obtained by traditional ("golden standard") ex vivo methods (ELISA), and parameters, estimated from the series of images in vivo. Observed correlation between these parameters and HER2 overexpression substantiates application of our approach to quantify HER2 concentration in vivo. C1 [Chernomordik, Victor; Hassan, Moinuddin; Gandjbakhche, Amir] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Analyt & Funct Biophoton, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD USA. RP Chernomordik, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Analyt & Funct Biophoton, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD USA. EM vchern@helix.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7957-0 J9 P SOC PHOTO-OPT INS PY 2010 VL 7561 AR 756118 DI 10.1117/12.855652 PG 6 WC Chemistry, Physical; Microscopy; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Microscopy; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSS15 UT WOS:000285579800023 ER PT S AU Baum, BJ Adriaansen, J Cotrim, AP Goldsmith, CM Perez, P Qi, SR Rowzee, AM Zheng, CY AF Baum, Bruce J. Adriaansen, Janik Cotrim, Ana P. Goldsmith, Corinne M. Perez, Paola Qi, Senrong Rowzee, Anne M. Zheng, Changyu BE Seymour, GJ Cullinan, MP Heng, NCK TI Gene Therapy of Salivary Diseases SO ORAL BIOLOGY: MOLECULAR TECHNIQUES AND APPLICATIONS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Gene therapy; salivary glands; adenovirus; adeno-associated virus; radiation damage; salivary hypofunction ID ADENOASSOCIATED VIRUS VECTORS; SJOGRENS-SYNDROME; PROTECTION; GLANDS; TEMPOL; MODEL AB For many years, our laboratory has been developing gene transfer approaches for salivary gland disorders that currently lack effective therapy. The purpose of this chapter is to describe key methods used in this developmental process. Specifically, we focus on one clinical condition, irradiation-induced salivary hypofunction, and address the choice of transgene and vector to be used, the construction of recombinant viral vectors, how vector delivery is accomplished, and methods for assessing vector function in vitro and in an appropriate animal model. C1 [Baum, Bruce J.; Adriaansen, Janik; Cotrim, Ana P.; Goldsmith, Corinne M.; Perez, Paola; Qi, Senrong; Rowzee, Anne M.; Zheng, Changyu] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. FU Intramural NIH HHS NR 14 TC 8 Z9 8 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-819-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 666 BP 3 EP 20 DI 10.1007/978-1-60761-820-1_1 D2 10.1007/978-1-60761-820-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA BQU39 UT WOS:000281865600001 PM 20717774 ER PT B AU Chen, Z Ehsanian, R Van Waes, C AF Chen, Zhong Ehsanian, Reza Van Waes, Carter BE Myers, F TI Nuclear Transcription Factors and Signaling Pathways in Oral Cancer Metastasis SO ORAL CANCER METASTASIS LA English DT Article; Book Chapter ID SQUAMOUS-CELL CARCINOMA; HEPATOCYTE GROWTH-FACTOR; FACTOR-KAPPA-B; FACTOR SCATTER FACTOR; RECEPTOR TYROSINE KINASE; PROINFLAMMATORY CYTOKINE EXPRESSION; TUMOR-STROMAL INTERACTIONS; HOST ENVIRONMENT PROMOTES; FOCAL ADHESION KINASE; HUMAN PROSTATE-CANCER AB Tumor progression of oral and other head and neck squamous cell carcinomas (HNSCCs) from dysplasia to metastasis involves a series of pathologic phenotypic changes considered to be the hallmarks of cancer, and these have been associated with a number of genetic, epigenetic, and molecular alterations (Fig. 10.1). Pathologic phenotypic changes precede metastasis and include increased cell proliferation, survival, and horizontal spread, which require certain molecular changes that together with later events contribute to the metastatic phenotype. These steps commonly include altered expression of molecules regulating the cell cycle and death (e.g., p53), growth factor response (epidermal growth factor receptor, EGFR), protein synthesis and metabolism (mammalian targets of rapamycin, mTOR), and cell immortality (telomerase). The subsequent steps of invasion and metastasis involve penetration and breakdown of the extracellular matrix (ECM) comprising the basement membrane and interstitial connective tissue; formation and invasion of a new stroma of host inflammatory and mesenchymal cells; neoangiogenesis and lymphangiogenesis; and distant spread via these lymphatics and blood vessels to secondary regional and distant sites. The molecular events accompanying the metastatic stage commonly include loss of expression or function of tumor suppressor genes or increased expression or function of oncogenes including numerous growth factors, cytokines, cell adhesion molecules and proteases, signal kinases, and nuclear transcription factors. Nuclear transcription factors appear to play a central role in malignant transformation and metastasis, since direct overexpression, mutation or activation of these molecules, or components of various upstream signaling pathways that modulate their function (Chaps. 8, 9, 11, 13) result in altered regulation of expression of diverse gene programs that produce the phenotypic changes characteristic of cancer and metastasis (Chaps. 4, 5, 12-14). C1 [Chen, Zhong; Ehsanian, Reza; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, 10 Ctr Dr,CRC Room 4-2732, Bethesda, MD 20892 USA. EM chenz@nidcd.nih.gov; ehsanianr@nidcd.nih.gov; vanwaesc@nidcd.nih.gov NR 162 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0774-5 PY 2010 BP 197 EP 229 DI 10.1007/978-1-4419-0775-2_10 D2 10.1007/978-1-4419-0775-2 PG 33 WC Oncology; Otorhinolaryngology; Surgery SC Oncology; Otorhinolaryngology; Surgery GA BNK36 UT WOS:000274790800010 ER PT J AU Michael, A Bajracharya, SD Yuen, PST Zhou, H Star, RA Illei, GG Alevizos, I AF Michael, A. Bajracharya, S. D. Yuen, P. S. T. Zhou, H. Star, R. A. Illei, G. G. Alevizos, I. TI Exosomes from human saliva as a source of microRNA biomarkers SO ORAL DISEASES LA English DT Article DE salivary exosomes; microRNA; biomarkers ID DIAGNOSTIC BIOMARKERS; URINARY EXOSOMES; PROSTATE-CANCER; CELLS; RNAS; MICROVESICLES; IMMUNOLOGY; EXPRESSION; SIGNATURES; PROTEINS AB Objective: The aim of this study was to examine the presence of microRNAs (miRNAs) within exosomes isolated from human saliva and to optimize and test methods for successful downstream applications. Design: Exosomes isolated from fresh and frozen glandular and whole human saliva were used as a source of miRNAs. The presence of miRNAs was validated with TaqMan quantitative PCR and miRNA microarrays. Results: We successfully isolated exosomes from human saliva from healthy controls and a patient with Sjogren's syndrome. microRNAs extracted from the exosomal fraction were sufficient for quantitative PCR and microarray profiling. Conclusions: The isolation of miRNAs from easily and non-invasively obtained salivary exosomes with subsequent characterization of the miRNA expression patterns is promising for the development of future biomarkers of the diagnosis and prognosis of various salivary gland pathologies. C1 [Michael, A.; Bajracharya, S. D.; Illei, G. G.; Alevizos, I.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA. [Yuen, P. S. T.; Zhou, H.; Star, R. A.] NIDDKD, Renal Diagnost & Therapeut Unit, Bethesda, MD 20892 USA. RP Alevizos, I (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Clin, NIH, 10 Ctr Dr,1N110, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov; alevizosi@nidcr.nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU NIDCR, NIH FX We would like to thank Stefanie Alexander and Dr Oscar Cheng for their technical assistance and suggestions. This research was supported by the Intramural Research Program of the NIDCR, NIH. NR 23 TC 203 Z9 223 U1 6 U2 32 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2010 VL 16 IS 1 BP 34 EP 38 DI 10.1111/j.1601-0825.2009.01604.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 534AA UT WOS:000272866700006 PM 19627513 ER PT J AU Baum, BJ Zheng, CY Alevizos, I Cotrim, AP Liu, SY McCullagh, L Goldsmith, CM McDermott, N Chiorini, JA Nikolov, NP Illei, GG AF Baum, Bruce J. Zheng, Changyu Alevizos, Ilias Cotrim, Ana P. Liu, Shuying McCullagh, Linda Goldsmith, Corinne M. McDermott, Nancy Chiorini, John A. Nikolov, Nikolay P. Illei, Gabor G. TI Development of a gene transfer-based treatment for radiation-induced salivary hypofunction SO ORAL ONCOLOGY LA English DT Review DE Xerostomia; Radiation; Gene therapy; Aquaporin-1; Adenovirus; Oral cancer ID ADENOVIRAL-MEDIATED TRANSFER; INCREASED FLUID SECRETION; RAT SUBMANDIBULAR-GLAND; HUMAN AQUAPORIN-1 CDNA; PAROTID-GLANDS; NONHUMAN-PRIMATES; NECK RADIOTHERAPY; EPITHELIAL-CELLS; TRANSFER VECTORS; LOCAL-DELIVERY AB A significant long-term side effect of radiation therapy for head and neck cancers is xerostomia, a dry mouth, due to salivary gland damage. Despite continuing efforts to eliminate this problem, many patients continue to suffer. This brief review describes our efforts to develop a gene transfer approach, employing the aquaporin-1 cDNA, to treat patients with existing radiation-induced salivary hypofunction. A Phase I/II clinical trial, using a recombinant adenoviral vector to mediate gene transfer, is currently underway. Published by Elsevier Ltd. C1 [Baum, Bruce J.; Zheng, Changyu; Alevizos, Ilias; Cotrim, Ana P.; Liu, Shuying; McCullagh, Linda; Goldsmith, Corinne M.; Chiorini, John A.; Nikolov, Nikolay P.; Illei, Gabor G.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1N113,MSC-1190,10 Ctr Dr, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU National Institute of Dental and Craniofacial Research FX This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research. NR 38 TC 23 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD JAN PY 2010 VL 46 IS 1 BP 4 EP 8 DI 10.1016/j.oraloncology.2009.09.004 PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 536LM UT WOS:000273045900004 PM 19892587 ER PT J AU Foley, TL Yasgar, A Garcia, CJ Jadhav, A Simeonov, A Burkart, MD AF Foley, Timothy L. Yasgar, Adam Garcia, Christopher J. Jadhav, Ajit Simeonov, Anton Burkart, Michael D. TI Preparation of FRET reporters to support chemical probe development SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID PHOSPHOPANTETHEINYL TRANSFERASE; PEPTIDES; BIOSYNTHESIS; DERIVATIVES; INHIBITION AB In high throughput screening (HTS) campaigns, the quality and cost of commercial reagents suitable for pilot studies often create obstacles upon scale-up to a full screen. We faced such challenges in our efforts to implement HTS for inhibitors of the phosphopantetheinyl transferase Sfp using an assay that had been validated using commercially available reagents. Here we demonstrate a facile route to the synthetic preparation of reactive tetraethylrhodamine and quencher probes, and their application to economically produce fluorescent and quencher-modified substrates. These probes were prepared on a scale that would allow a full, quantitative HTS of more than 350,000 compounds. C1 [Foley, Timothy L.; Garcia, Christopher J.; Burkart, Michael D.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Yasgar, Adam; Jadhav, Ajit; Simeonov, Anton] NIH Chem Genom Ctr, Bethesda, MD USA. RP Burkart, MD (reprint author), Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM mburkart@ucsd.edu FU NIH [R01GM086225, R03MH83266, R21AI090213] FX This work was funded by NIH R01GM086225, R03MH83266, and R21AI090213. The authors wish to thank Drs. Yongxuan Su (UCSD Small Molecule Mass Spectrometry Facility) and William Leister (NIH Chemical Genomics Center) for performing mass spectrometric analyses; and Elizabeth Komives (UCSD) for assistance with peptide synthesis. NR 28 TC 17 Z9 17 U1 0 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2010 VL 8 IS 20 BP 4601 EP 4606 DI 10.1039/c0ob00322k PG 6 WC Chemistry, Organic SC Chemistry GA 656GJ UT WOS:000282315900019 PM 20725690 ER PT J AU Nandurdikar, RS Maciag, AE Hong, SY Chakrapani, H Citro, ML Keefer, LK Saavedra, JE AF Nandurdikar, Rahul S. Maciag, Anna E. Hong, Sam Y. Chakrapani, Harinath Citro, Michael L. Keefer, Larry K. Saavedra, Joseph E. TI Glycosylated PROLI/NO Derivatives as Nitric Oxide Prodrugs SO ORGANIC LETTERS LA English DT Article ID DIAZENIUMDIOLATE FAMILY; NOBEL LECTURE; DONOR DRUGS; TRENDS AB GlcNAc-PROLI/NO prodrugs that are activated by N-acetylglucosaminidase to release nitric oxide (NO) are described. A classical acid-amine coupling is used to bifunctionalize these PROLI/NO prodrugs, which on activation generate up to 4 mol of NO, a peptide residue, and an N-acetylglucosamine residue. Many of the prodrugs synthesized are efficient sources of intracellular NO. C1 [Nandurdikar, Rahul S.; Hong, Sam Y.; Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Maciag, Anna E.; Citro, Michael L.; Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21702 USA. [Chakrapani, Harinath] Indian Inst Sci Educ & Res, Dept Chem, Pune 411008, Maharashtra, India. RP Nandurdikar, RS (reprint author), NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM nandurdikarr@mail.nih.gov; saavedjo@mail.nih.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NLH, National Cancer Institute, Center for Cancer Research FX This project has been funded with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E, and by the Intramural Research Program of the NLH, National Cancer Institute, Center for Cancer Research. We are grateful to Ms. Susan Kenney, NCI-Frederick Screening Technology Branch, for providing us the cell line. NR 20 TC 4 Z9 4 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JAN 1 PY 2010 VL 12 IS 1 BP 56 EP 59 DI 10.1021/ol902481s PG 4 WC Chemistry, Organic SC Chemistry GA 534ZV UT WOS:000272937200015 PM 19954198 ER PT J AU Nuka, S Zhou, W Henry, SP Gendron, CM Schultz, JB Shinomura, T Johnson, J Wang, Y Keene, DR Ramirez-Solis, R Behringer, RR Young, MF Hook, M AF Nuka, S. Zhou, W. Henry, S. P. Gendron, C. M. Schultz, J. B. Shinomura, T. Johnson, J. Wang, Y. Keene, D. R. Ramirez-Solis, R. Behringer, R. R. Young, M. F. Hoeoek, M. TI Phenotypic characterization of epiphycan-deficient and epiphycan/biglycan double-deficient mice SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Osteoarthritis; Cartilage; Mouse; Microarray; Small leucine-rich proteoglycans ID HUMAN OSTEOARTHRITIC CARTILAGE; DERMATAN SULFATE PROTEOGLYCAN; ACID REPEAT POLYMORPHISM; GROWTH-FACTOR-BETA; ARTICULAR-CARTILAGE; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; EPIPHYSEAL CARTILAGE; MOLECULAR-CLONING; II COLLAGEN AB Objective: To characterize the in vivo role epiphycan (Epn) has in cartilage development and/or maintenance. Methods: Epn-deficient mice were generated by disrupting the Epn gene in mouse embryonic stem cells. Epn(biglycan (Bgn) double-deficient mice were produced by crossing Epn-deficient mice with Bgn-deficient mice. Whole knee joint histological sections were stained using van Gieson or Fast green/Safranin-O to analyze collagen or proteoglycan content, respectively. Microarray analysis was performed to detect gene expression changes within knee joints. Results: Epn-deficient and Epn/Bgn double-deficient mice appeared normal at birth. No significant difference in body weight or femur length was detected in any animal at 1 month of age. However, 9-month Epn/Bgn double-deficient mice were significantly lighter and had shorter femurs than wild type mice, regardless of gender. Male Epn-deficient mice also had significantly shorter femurs than wild type mice at 9 months. Most of the deficient animals developed osteoarthritis (OA) with age; the onset of OA was observed earliest in Epn/Bgn double-deficient mice. Message RNA isolated from Epn/Bgn double-deficient knee joints displayed increased matrix protein expression compared with wild type mice, including other small leucine-rich proteoglycan (SLRP) members such as asporin, fibromodulin and lumican. Conclusion: Similar to other previously studied SLRPs, EPN plays an important role in maintaining joint integrity. However, the severity of the OA phenotype in the Epn/Bgn double-deficient mouse suggests a synergy between these two proteins. These data are the first to show a genetic interaction involving class I and class III SLRPs in vivo. (C) 2009 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. C1 [Nuka, S.; Zhou, W.; Henry, S. P.; Gendron, C. M.; Schultz, J. B.; Shinomura, T.; Johnson, J.; Ramirez-Solis, R.; Hoeoek, M.] Texas A&M Univ Syst Hlth Sci Ctr, Ctr Extracellular Matrix Biol, Albert B Alkek Inst Biosci & Technol, Houston, TX 77030 USA. [Wang, Y.; Behringer, R. R.] Univ Texas MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. [Keene, D. R.] Shriners Hosp Children, Portland, OR 97239 USA. [Young, M. F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hook, M (reprint author), Texas A&M Univ Syst Hlth Sci Ctr, Ctr Extracellular Matrix Biol, Albert B Alkek Inst Biosci & Technol, 2121 W Holcombe Blvd, Houston, TX 77030 USA. EM mhook@ibt.tamhsc.edu FU NIH [P01AR042919, R01AR047433] FX Funding sources: This work was supported by NIH grants P01AR042919 and R01AR047433. NR 51 TC 18 Z9 18 U1 5 U2 13 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JAN PY 2010 VL 18 IS 1 BP 88 EP 96 DI 10.1016/j.joca.2009.11.006 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 544RT UT WOS:000273677500014 PM 19932218 ER PT S AU Bauer, AK Kleeberger, SR AF Bauer, Alison K. Kleeberger, Steven R. BE Laskin, DL TI Genetic mechanisms of susceptibility to ozone-induced lung disease SO OXIDATIVE/NITROSATIVE STRESS AND DISEASE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 4th International Conference on Oxidative/Nitrosative Stress and Disease CY OCT 28-30, 2009 CL New York Acad Sci, New York, NY HO New York Acad Sci DE air pollution; gene; oxidants; pulmonary; inbred mouse; inflammation ID TOLL-LIKE RECEPTOR-4; AIR-POLLUTION; OXIDATIVE STRESS; INBRED MICE; INJURY; INFLAMMATION; POLYMORPHISMS; EXPOSURE; HYPERPERMEABILITY; ASSOCIATION AB Environmental oxidants remain a major public health concern in industrialized cities throughout the world. Population and epidemiological studies have associated oxidant air pollutants with morbidity and mortality outcomes, and underscore the important detrimental effects of these pollutants on the lung. Interindividual variation in pulmonary responses to air pollutants suggests that some subpopulations are at increased risk to detrimental effects of pollutant exposure, and it has become clear that genetic background is an important susceptibility factor. A number of genetics and genomics tools have recently emerged to enable identification of genes that contribute to differential responsiveness to oxidants, including ozone (O-3). Integrative omics approaches have been applied in inbred mice to identify genes that determine differential responsiveness to O-3-induced injury and inflammation, including Tnf, Tlr4, and MHC Class II genes. Combined investigations across cell models, inbred mice, and humans have provided, and will continue to provide, important insight to understanding genetic factors that contribute to differential susceptibility to oxidants. C1 [Bauer, Alison K.] Michigan State Univ, Dept Pathobiol & Diagnost Invest, E Lansing, MI 48824 USA. RP Kleeberger, SR (reprint author), NIEHS, 111 TW Alexander Dr,Bldg 101,MD-201, Res Triangle Pk, NC 27709 USA. EM kleeber1@niehs.nih.gov FU NIEHS NIH HHS [K22 ES014731-03] NR 39 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-784-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1203 BP 113 EP 119 DI 10.1111/j.1749-6632.2010.05606.x PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Science & Technology - Other Topics GA BTN06 UT WOS:000287380600017 PM 20716292 ER PT J AU Mikolajczyk, RT Louis, GMB Cooney, MA Lynch, CD Sundaram, R AF Mikolajczyk, Rafael T. Louis, Germaine M. Buck Cooney, Maureen A. Lynch, Courtney D. Sundaram, Rajeshwari TI Characteristics of prospectively measured vaginal bleeding among women trying to conceive SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE cycle length; fecundity; gestation; menstruation; time to pregnancy; vaginal bleeding ID MENSTRUAL DIARY DATA; GESTATIONAL-AGE; PREGNANCY; FERTILITY AB P>Previous research has described variability in menstrual cycle lengths within and across women, though less attention has focused on characterising patterns of bleeding. While clinical definitions for menstrual bleeding are often given in standard textbooks, the validity of conventional definitions has not been empirically evaluated in epidemiological studies. The definition of menstrual bleeding may affect the analysis of time to pregnancy and pregnancy dating that relies upon the last menstrual period. We used daily records of vaginal bleeding from a prospective cohort study that included 74 women trying to become pregnant who reported 430 bleeding episodes. A longitudinal mixture model (PROC TRAJ) was used to classify patterns of bleeding. Among the first 74 bleeding episodes, 15% comprised only days with spotting or light bleeding (possibly representing non-menstrual bleeding given the length of the cycle defined by these bleeding episodes). When all 430 bleeding episodes were analysed, four distinct bleeding patterns emerged: (1) episodic bleeding comprising 1-3 days of spotting (10%), (2) bleeding lasting 3-6 days (40%), (3) bleeding lasting 6-8 days (33%), and (4) bleeding lasting 8-12 days (17%). These findings suggest that non-menstrual bleeding may be relatively common. Considerable variation in menstrual bleeding patterns is evident, and as such is likely to impact fecundity-related endpoints or gestational age estimates that rely upon menstrual cycle dates. The association between bleeding patterns and female fecundity awaits future research. C1 [Mikolajczyk, Rafael T.] Univ Bielefeld, Dept Publ Hlth Med, Sch Publ Hlth, D-33501 Bielefeld, Germany. [Louis, Germaine M. Buck; Cooney, Maureen A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA. [Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, NIH, Bethesda, MD USA. [Lynch, Courtney D.] Ohio State Univ, Div Epidemiol, Coll Publ Hlth, Columbus, OH 43210 USA. RP Mikolajczyk, RT (reprint author), Univ Bielefeld, Dept Publ Hlth Med, Sch Publ Hlth, POB 100131, D-33501 Bielefeld, Germany. EM rmikolajczyk@uni-bielefeld.de OI Mikolajczyk, Rafael/0000-0003-1271-7204; Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, Bethesda, MD, USA; Epidemiology Branch FX This study was supported by the Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, Bethesda, MD, USA. Dr Mikolajczyk's work was performed during a postdoctoral fellowship at the Epidemiology Branch of the above institute. NR 21 TC 4 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2010 VL 24 IS 1 BP 24 EP 30 DI 10.1111/j.1365-3016.2009.01074.x PG 7 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 538JL UT WOS:000273180300003 PM 20078826 ER PT J AU Hasan, R Funk, MLJ Herring, AH Olshan, AF Hartmann, KE Baird, DD AF Hasan, Reem Funk, Michele L. Jonsson Herring, Amy H. Olshan, Andrew F. Hartmann, Katherine E. Baird, Donna D. TI Accuracy of reporting bleeding during pregnancy SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE prenatal vaginal bleeding; retrospective recall; accuracy ID MISCARRIAGE AB P>Hasan R, Jonsson Funk ML, Herring AH, Olshan AF, Hartmann KE, Baird DD. Accuracy of reporting bleeding during pregnancy. Paediatric and Perinatal Epidemiology 2010; 24: 31-34. Vaginal bleeding during pregnancy has been considered a marker of an at-risk pregnancy, but the accuracy of reported bleeding has not been assessed. We sought to evaluate the agreement in vaginal bleeding reports based on prospective daily diary and retrospective recall at first-trimester interview and to investigate predictors of reporting accuracy. Participants recruited prior to pregnancy for a community-based pregnancy cohort (n = 153) completed web-based daily diaries beginning before pregnancy until the end of the first trimester. A comprehensive first-trimester interview was conducted, and the bleeding data from diary and interview were compared. Kappa statistics were used to quantify agreement. Log-linear models were used to investigate maternal age, prior miscarriage, and current pregnancy outcome as potential predictors of agreement. We found that bleeding characteristics (number of bleeding episodes, bleeding heaviness, duration and gestational timing) from the diary and interview were reported with high levels of agreement. Kappas ranged from 0.77 to 0.84. Retrospective report of any bleeding had a sensitivity of 0.80 and specificity of 1.0; however, sensitivity was lower when examined within smaller time intervals. Important predictors of agreement were not identified in this analysis, but the sample was small. Overall, the presence of vaginal bleeding, a common and potentially alarming symptom of early pregnancy, may be assessed by interview later in pregnancy with reasonable accuracy. C1 [Hasan, Reem; Baird, Donna D.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Hasan, Reem; Funk, Michele L. Jonsson; Olshan, Andrew F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Herring, Amy H.; Olshan, Andrew F.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. [Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Nashville, TN USA. [Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37232 USA. RP Hasan, R (reprint author), NIEHS, Epidemiol Branch, MD A3-05, Res Triangle Pk, NC 27709 USA. EM reem_hasan@med.unc.edu RI Jonsson Funk, Michele/F-6885-2011; Baird, Donna/D-5214-2017 OI Jonsson Funk, Michele/0000-0002-3756-7540; Baird, Donna/0000-0002-5544-2653 FU National Institute of Child and Human Development [5R01HD043883, 5R01HD049675]; American Water Works Association Research Foundation [2579]; National Institute of Environmental Health Sciences [P30ES10126] FX The field research was supported in part by grants from the National Institute of Child and Human Development (5R01HD043883 and 5R01HD049675) and the American Water Works Association Research Foundation (2579). Additional funds were provided by the National Institute of Environmental Health Sciences (Intramural Research Program and P30ES10126). NR 10 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2010 VL 24 IS 1 BP 31 EP 34 DI 10.1111/j.1365-3016.2009.01089.x PG 4 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 538JL UT WOS:000273180300004 PM 20078827 ER PT J AU Zhang, YQ Guo, N Peng, GD Wang, XD Han, M Raincrow, J Chiu, CH Coolen, LM Wenthold, RJ Zhao, ZQ Jing, NH Yu, L AF Zhang, Yu-Qiu Guo, Ning Peng, Guangdun Wang, Xidao Han, Mei Raincrow, Jeremy Chiu, Chi-hua Coolen, Lique M. Wenthold, Robert J. Zhao, Zhi-Qi Jing, Naihe Yu, Lei TI Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain (vol 146, pg 130, 2009) SO PAIN LA English DT Correction C1 [Guo, Ning; Raincrow, Jeremy; Chiu, Chi-hua; Yu, Lei] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. [Guo, Ning; Raincrow, Jeremy; Chiu, Chi-hua; Yu, Lei] Rutgers State Univ, Ctr Alcohol Studies, Piscataway, NJ 08854 USA. [Zhang, Yu-Qiu; Guo, Ning; Coolen, Lique M.; Yu, Lei] Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH USA. [Zhang, Yu-Qiu; Han, Mei; Zhao, Zhi-Qi] Fudan Univ, Inst Neurobiol, Inst Brain Sci, Shanghai 200433, Peoples R China. [Zhang, Yu-Qiu; Han, Mei; Zhao, Zhi-Qi] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Peng, Guangdun; Wang, Xidao; Jing, Naihe] Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China. [Wenthold, Robert J.] NIDCD, Neurochem Lab, NIH, Bethesda, MD USA. RP Yu, L (reprint author), Rutgers State Univ, Dept Genet, 607 Allison Rd, Piscataway, NJ 08854 USA. EM lei.yu@rutgers.edu NR 1 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2010 VL 148 IS 1 BP 176 EP 176 DI 10.1016/j.pain.2009.10.022 PG 1 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 547LH UT WOS:000273889300028 ER PT B AU Perez, MA Cohen, LG AF Perez, Monica A. Cohen, Leonardo G. BE Knotkova, H Cruciani, R Merrick, J TI PRINCIPLES AND MECHANISMS OF TRANSCRANIAL MAGNETIC STIMULATION SO PAIN: BRAIN STIMULATION IN THE TREATMENT OF PAIN SE Disability Studies LA English DT Article; Book Chapter ID HUMAN MOTOR CORTEX; PAIRED-PULSE INHIBITION; THETA-BURST-STIMULATION; LOWER-LIMB MOTONEURONS; LOW-FREQUENCY RTMS; INTRACORTICAL INHIBITION; CORTICAL STIMULATION; INTERHEMISPHERIC INHIBITION; CORTICOSPINAL EXCITABILITY; PROCEDURAL KNOWLEDGE C1 [Perez, Monica A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Ctr Neural Basis Cognit, Pittsburgh, PA 15261 USA. [Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. RP Perez, MA (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, Ctr Neural Basis Cognit, Pittsburgh, PA 15261 USA. EM perezmo@pitt.edu NR 64 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-690-1 J9 DISABIL STUD PY 2010 BP 113 EP 127 PG 15 WC Neurosciences SC Neurosciences & Neurology GA BPD27 UT WOS:000278554700009 ER PT J AU Ramsden, C Gagnon, C Graciosa, J Faurot, K David, R Bralley, JA Harden, RN AF Ramsden, Christopher Gagnon, Christine Graciosa, Joseph Faurot, Keturah David, Robert Bralley, J. Alexander Harden, R. Norman TI Do Omega-6 and Trans Fatty Acids Play a Role in Complex Regional Pain Syndrome? A Pilot Study SO PAIN MEDICINE LA English DT Article DE CRPS; Omega-6; Omega-3; Trans Fatty Acids; Arachidonic Acid; Chronic Pain ID ALPHA-LINOLENIC ACID; ARACHIDONIC-ACID; FRONTAL-CORTEX; FISH-OIL; CENTRAL SENSITIZATION; CEREBROSPINAL-FLUID; PROSTAGLANDIN E-2; IMMUNE CELLS; ION CHANNELS; SPINAL-CORD AB Objectives. The study aims to compare the omega-6 (n-6) and omega-3 (n-3) highly unsaturated fatty acids (HUFA), and trans fatty acid (trans FA) status of Complex Regional Pain Syndrome (CRPS) patients to pain-free controls. Design. Case control study. Setting. The setting was at a multidisciplinary rehabilitation center. Patients. Twenty patients that met the Budapest research diagnostic criteria for CRPS and 15 pain-free control subjects were included in this study. Outcome Measures. Fasting plasma fatty acids were collected from all participants. In CRPS patients, pain was assessed using the McGill Pain Questionnaire-Short Form. In addition, results from the perceived disability (Pain Disability Index), pain-related anxiety (Pain Anxiety Symptom Scale Short Form), depression (Center for Epidemiologic Studies Depression Scale Short Form), and quality of life (Short Form-36 [SF-36]) were evaluated. Results. Compared with controls, CRPS patients demonstrated elevated concentrations of n-6 HUFA and trans FA. No differences in n-3 HUFA concentrations were observed. Plasma concentrations of the n-6 HUFA docosatetraenoic acid were inversely correlated with the "vitality" section of the SF-36. Trans FA concentrations positively correlated with pain-related disability and anxiety. Conclusion. These pilot data suggest that elevated n-6 HUFA and trans FA may play a role in CRPS pathogenesis. These findings should be replicated, and more research is needed to explore the clinical significance of low n-6 and trans FA diets with or without concurrent n-3 HUFA supplementation, for the management of CRPS. C1 [Ramsden, Christopher; Gagnon, Christine; Harden, R. Norman] NW Univ Feinberg, Sch Med, Dept Phys Med & Rehabil, Rehabil Inst Chicago, Chicago, IL USA. [Faurot, Keturah] Univ N Carolina, Sch Med, Dept Phys Med & Rehabil, Program Integrat Med, Chapel Hill, NC USA. [David, Robert; Bralley, J. Alexander] Metametrix Clin Lab, Atlanta, GA USA. RP Ramsden, C (reprint author), NIH, MSC 2088,31 Ctr Dr,Rm 1B58, Bethesda, MD 20892 USA. EM chris.ramsden@nih.gov NR 76 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2010 VL 11 IS 7 BP 1115 EP 1125 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 615HI UT WOS:000279125000017 PM 20545870 ER PT S AU Hofmann, JN Keifer, MC Checkoway, H De Roos, AJ Farin, FM Fenske, RA Richter, RJ van Belle, G Furlong, CE AF Hofmann, Jonathan N. Keifer, Matthew C. Checkoway, Harvey De Roos, Anneclaire J. Farin, Federico M. Fenske, Richard A. Richter, Rebecca J. van Belle, Gerald Furlong, Clement E. BE Reddy, ST TI Biomarkers of Sensitivity and Exposure in Washington State Pesticide Handlers SO PARAOXONASES IN INFLAMMATION, INFECTION, AND TOXICOLOGY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 3rd International Conference on Paraoxonases CY SEP 07-10, 2008 CL Univ Calif Los Angeles, Los Angeles, CA SP US Def Dept, Def Threat Reduct Agcy, Bristol Myers Squibb HO Univ Calif Los Angeles DE Agriculture; Cholinesterase; Farm workers; Gene-environment interaction; Organophosphates; Paraoxonase (PON1); Pesticides ID HUMAN-SERUM PARAOXONASE; PON1 STATUS; ORGANOPHOSPHATE TOXICITY; CHLORPYRIFOS-OXON; POLYMORPHISM; GENE; ASSOCIATION; WORKERS; HEALTH; SUSCEPTIBILITY AB Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are widely used in agriculture in the US and abroad. These compounds which inhibit acetylcholinestersase (AChE) enzyme activity continue to be responsible for a high proportion of pesticide poisonings among US agricultural workers. It is possible that some individuals may be especially susceptible to health effects related to OP/CB exposure. The paraoxonase (PUN 1) enzyme metabolizes the highly toxic oxon forms of some OPs, and an individual's PON1 status may be an important determinant of his or her sensitivity to these chemicals. This chapter discusses methods used to characterize the PUN I status of individuals and reviews previous epidemiologic studies that have evaluated PON1-related sensitivity to OPs in relation to various health endpoints. It also describes an ongoing longitudinal study among OP-exposed agricultural pesticide handlers who are participating in a recently implemented cholinesterase monitoring program in Washington State. This study will evaluate handlers' PUN I status as a hypothesized determinant of butyrylcholinesterase (BuChE) inhibition. Such studies will be useful to determine how regulatory risk assessments might account for differences in PON1-related OP sensitivity when characterizing inter-individual variability in risk related to OP exposure. Recent work assessing newer and more sensitive biomarkers of OP exposure is also discussed briefly in this chapter. C1 [Hofmann, Jonathan N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Richter, Rebecca J.; Furlong, Clement E.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Richter, Rebecca J.; Furlong, Clement E.] Univ Washington, Dept Genome Sci, Div Med Genet, Seattle, WA 98195 USA. [Checkoway, Harvey; De Roos, Anneclaire J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Keifer, Matthew C.; Checkoway, Harvey; Farin, Federico M.; Fenske, Richard A.; van Belle, Gerald] Univ Washington, Dept Environm, Seattle, WA 98195 USA. [van Belle, Gerald] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Keifer, Matthew C.; Checkoway, Harvey; Farin, Federico M.; Fenske, Richard A.; van Belle, Gerald] Univ Washington, Dept Occupat Hlth, Seattle, WA 98195 USA. RP Hofmann, JN (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM hofmannjn@mail.nih.gov; mkeifer@u.washington.edu; checko@u.washington.edu; deroos@u.washington.edu; freddy@u.washington.edu; rfenske@u.washington.edu; rrichter@u.washington.edu; vanbelle@u.washington.edu; clem@u.washington.edu FU CDC/NIOSH [U50OH07544, T42OH008433]; NIEHS [P30ES07033, T32ES07262, P42ES04696, ES009883] FX We would like to thank all of the workers who participated in this study. We also acknowledge the following individuals who contributed to this study: Zahra Afsharinejad for her work on the PON1 genotyping assays; Kelly Fryer-Edwards for her assistance with outreach to study participants; Pam Ernst and Joe Cozzetto from Central Washington Occupational Medicine for their assistance with our recruitment efforts; and Maria Negrete and Pablo Palmandez from the Pacific Northwest Agricultural Safety and Health Center for their assistance with field data collection. Financial support for this project was provided by CDC/NIOSH grants U50OH07544 and T42OH008433, and NIEHS grants P30ES07033, T32ES07262, P42ES04696, and ES009883. NR 50 TC 5 Z9 5 U1 0 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-60761-349-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 660 BP 19 EP 27 DI 10.1007/978-1-60761-350-3_3 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BOB96 UT WOS:000276140000003 PM 20221867 ER PT J AU Putnick, DL Bornstein, MH Hendricks, C Painter, KM Suwalsky, JTD Collins, WA AF Putnick, Diane L. Bornstein, Marc H. Hendricks, Charlene Painter, Kathleen M. Suwalsky, Joan T. D. Collins, W. Andrew TI Stability, Continuity, and Similarity of Parenting Stress in European American Mothers and Fathers Across Their Child's Transition to Adolescence SO PARENTING-SCIENCE AND PRACTICE LA English DT Article ID GENDER-DIFFERENCES; MARITAL QUALITY; FAMILY; CONFLICT; SATISFACTIONS; PERCEPTIONS; ADJUSTMENT; AUTONOMY; MODEL; SCALE AB Objective. Experiencing some degree of parenting stress is virtually unavoidable, particularly as children enter early adolescence and assert their independence. In this study, the authors examined how parenting stress attributed to the parent, the child, or the dyad changed in mean level and relative standing across their child's transition to adolescence. The authors also compared mothers and fathers from the same families in terms of parenting stress and explored how one parent's stress affected the other parent's stress. Design. Participants included 222 European American parents (111 mothers and 111 fathers), assessed when their children were 10 and 14 years old. Results. Parenting stress was highly stable from 10 to 14 years. Total parenting stress increased across time, and was attributable to stress due to increased parent-child dysfunctional interaction, not parental distress or stress due to child behavior. Mothers and fathers agreed moderately in their relative standing and in the average levels of parenting stress in the 3 different domains of parenting stress at each time point. Mothers' and fathers' stress across domains were sometimes related. Conclusions. Mothers' and fathers' increased parenting stress across their child's transition to adolescence seems to derive from parent-child interaction rather than qualities of the parent or the child per se. Finding ways to maintain parent-child communication and closeness may protect parents and families from increased stress during this vulnerable time. C1 [Putnick, Diane L.; Bornstein, Marc H.; Hendricks, Charlene; Painter, Kathleen M.; Suwalsky, Joan T. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Collins, W. Andrew] Univ Minnesota, Minneapolis, MN 55455 USA. RP Putnick, DL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM putnickd@mail.nih.gov OI Putnick, Diane/0000-0002-6323-749X FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [R01 HD054850] NR 66 TC 11 Z9 11 U1 4 U2 12 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1529-5192 J9 PARENT-SCI PRACT JI Parent.-Sci. Pract. PY 2010 VL 10 IS 1 BP 60 EP 77 AR PII 918978296 DI 10.1080/15295190903014638 PG 18 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA 551AB UT WOS:000274175700004 PM 20191083 ER PT S AU Lenfant, C AF Lenfant, Claude BE Gehr, P Muhlfeld, C RothenRutishauser, B Blank, F TI Particle-Lung Interactions Second Edition Introduction SO PARTICLE-LUNG INTERACTIONS, 2ND EDITION SE Lung Biology in Health and Disease LA English DT Editorial Material; Book Chapter C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND SN 0362-3181 BN 978-1-4200-7257-0; 978-1-4200-7256-3 J9 LUNG BIOL HEALTH DIS PY 2010 VL 241 BP VII EP VII PG 1 WC Respiratory System SC Respiratory System GA BC9OZ UT WOS:000356722100001 ER PT B AU Omar, H Greydanus, DE Tsitsika, AK Patel, DR Merrick, J AF Omar, Hatim Greydanus, Donald E. Tsitsika, Artemis K. Patel, Dilip R. Merrick, Joav BE Omar, HA Greydanus, DE Tsitsika, AK Patel, DR Merrick, J TI PEDIATRIC AND ADOLESCENT SEXUALITY AND GYNECOLOGY: PRINCIPLES FOR THE PRIMARY CARE CLINICIAN INTRODUCTION SO PEDIATRIC AND ADOLESCENT SEXUALITY AND GYNECOLOGY: PRINCIPLES FOR THE PRIMARY CARE CLINICIAN SE Health and Human Development LA English DT Editorial Material; Book Chapter C1 [Omar, Hatim] Univ Kentucky, Coll Med, Kentucky Childrens Hosp, Dept Pediat,Adolescent Med Program, Lexington, KY 40506 USA. [Omar, Hatim] Univ Kentucky, Coll Med, Kentucky Childrens Hosp, Dept Pediat,Young Parent Program, Lexington, KY USA. [Greydanus, Donald E.; Patel, Dilip R.] Michigan State Univ, Coll Human Med, Kalamazoo, MI USA. [Tsitsika, Artemis K.] Childrens Hosp, Dept Pediat, Athens, Greece. [Merrick, Joav] Univ Kentucky, NICHHD, Off Med Director,Jerusalem & Kentucky Childrens H, Div Mental Retardat,Minist Social Affairs, Lexington, KY USA. RP Omar, H (reprint author), Univ Kentucky, Coll Med, Kentucky Childrens Hosp, Dept Pediat,Adolescent Med Program, Lexington, KY 40506 USA. EM haomar2@uky.edu; Greydanus@kcms.msu.edu; artspy@otenet.gr; patel@kcms.msu.edu; jmerrick@zahav.net.il; Greydanus@kcms.msu.edu; artspy@otenet.gr; patel@kcms.msu.edu; jmerrick@zahav.net.il NR 2 TC 3 Z9 3 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-735-9 J9 HEALTH HUM DEV PY 2010 BP XIII EP XVI PG 4 WC Medicine, General & Internal; Pediatrics SC General & Internal Medicine; Pediatrics GA BQP36 UT WOS:000281471400001 ER PT J AU Ehrlich, D Bruder, E Thome, MA Gutt, CN Doeberitz, MV Niggli, F Perantoni, AO Koesters, R AF Ehrlich, David Bruder, Elisabeth Thome, Martin A. Gutt, Carsten N. Doeberitz, Magnus von Knebel Niggli, Felix Perantoni, Alan O. Koesters, Robert TI Nuclear Accumulation of beta-Catenin Protein Indicates Activation of wnt Signaling in Chemically Induced Rat Nephroblastomas SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE beta-catenin; nephroblastoma; rat; wnt signaling; WT1 ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CARCINOMA CELLS; WILMS-TUMORS; CHILDHOOD-CANCER; NEPHRO-BLASTOMA; WT1 GENE; PATHWAY; TARGET; EXPRESSION; MUTATIONS AB Aberrant wnt signaling caused by mutations in CTNNB1 occurs in about 15% of Wilms tumors, and these mutations appear to be dependent on the concomitant mutational inactivation of the zinc-finger protein WTI. Nuclear beta-catenin protein, a substitute marker of active wnt signaling, has been detected in an even higher proportion (>50%) of Wilms tumors, suggesting alternative genetic pathways leading to beta-catenin activation. Thus, targeting wnt signaling may become an important future therapeutic strategy in Wilms tumor patients. Currently, chemically induced rat nephroblastomas provide the only available rodent model for this tumor. To determine the contribution of active wnt signaling in this model, we investigated 24 chemically induced rat nephroblastomas for beta-catenin protein expression and for Ctnnb1 and WT1 mutations. Immunohistochemistry showed focal strong nuclear accumulation of beta-catenin protein in 18 of 24 tumors, although in a heterogenous pattern. Blastemal and mesenchymal compartments displayed nuclear-positive cells more frequently than areas of epithelial differentiation. Interestingly, we found no mutation of exon 3 of Ctnnb1 and no mutation within the zinc-finger region of WT1 in any of the 24 tumors analyzed. In conclusion, our findings suggest activation of wnt signaling in the majority (63%) of chemically induced rat nephroblastomas. Nuclear expression of beta-catenin in the absence of Ctnnb1 mutations implies, however, alternate mutational targets in rat nephroblastomas. C1 [Ehrlich, David; Doeberitz, Magnus von Knebel; Koesters, Robert] Univ Heidelberg Hosp, Div Appl Tumor Biol, Inst Pathol, D-69120 Heidelberg, Germany. [Bruder, Elisabeth] Univ Basel Hosp, Inst Pathol, CH-4031 Basel, Switzerland. [Thome, Martin A.; Gutt, Carsten N.] Univ Heidelberg Hosp, Dept Gen Abdominal & Transplant Surg, D-69120 Heidelberg, Germany. [Niggli, Felix; Koesters, Robert] Childrens Hosp, CH-8032 Zurich, Switzerland. [Perantoni, Alan O.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Koesters, Robert] Univ Heidelberg Hosp, Inst Human Genet, D-69120 Heidelberg, Germany. RP Koesters, R (reprint author), Univ Heidelberg Hosp, Div Appl Tumor Biol, Inst Pathol, Neuenheimer Feld 220-221, D-69120 Heidelberg, Germany. EM robert.koesters@med.uni-heidelberg.de RI von Knebel Doeberitz, Magnus/D-2372-2016 OI von Knebel Doeberitz, Magnus/0000-0002-0498-6781 FU Intramural NIH HHS [ZIA BC005093-31] NR 43 TC 9 Z9 9 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD JAN-FEB PY 2010 VL 13 IS 1 BP 1 EP 8 DI 10.2350/08-03-0443.1 PG 8 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 574YM UT WOS:000276030100001 PM 19348510 ER PT J AU Meany, HJ Sackett, DL Maris, JM Ward, Y Krivoshik, A Cohn, SL Steinberg, SM Balis, FM Fox, E AF Meany, Holly J. Sackett, Dan L. Maris, John M. Ward, Yvona Krivoshik, Andrew Cohn, Susan L. Steinberg, Seth M. Balis, Frank M. Fox, Elizabeth TI Clinical Outcome in Children With Recurrent Neuroblastoma Treated With ABT-751 and Effect of ABT-751 on Proliferation of Neuroblastoma Cell Lines and on Tubulin Polymerization In Vitro SO PEDIATRIC BLOOD & CANCER LA English DT Article DE ABT-751; cytotoxicity; neuroblastoma; pediatric; tubulin ID PEDIATRIC-PATIENTS; DIVERSE PANEL; SOLID TUMORS; CYTOTOXICITY; E7010; MICROTUBULES; SULFONAMIDE; INHIBITION; MICROSCOPY; PROTEINS AB Background. ABT-751, an orally bioavailable sulfonamide, binds beta-tubulin to inhibit microtubule polymerization. We described response and event-free survival (EFS) in children with neuroblastoma and other solid tumors receiving ABT-751, assessed in vitro cytotoxicity of ABT-751 and evaluated the effect of ABT-751 on tubulin polymerization in peripheral blood mononuclear cells (PBMC) and pediatric tumor cell lines. Procedure. Patients with neuroblastoma (n = 50) or other solid tumors (n = 26) enrolled on the ABT-751 pediatric phase I and pilot trials were reviewed. The sulforhodamine B (SRB) and ACEA Real-Time Cell Electronic Sensing (RT-CES) assays were used to determine the in vitro cytotoxicity. Pharmacodynamic effects on tubulin polymerization/depolymerization were assessed by Western blot and confocal microscopy using antibodies specific for post-translational modifications of polymerized tubulin. Results. Forty-five patients with neuroblastoma were evaluated for anti-tumor response. No complete or partial responses were documented. The median EFS was 9.3 weeks for children with neuroblastoma and 3.3 weeks for children other solid tumors (P<0.0001). The ABT-751 IC(50) was 0.6-2.6 mcM in neuroblastoma and 0.7-4.6mcM in other solid tumor cell lines. Following drug exposure, polymerized tubulin decreased in a concentration- and time-dependent manner in cell lines. Conclusions. In children treated with ABT-751, the EFS is longer in children with neuroblastoma as compared to other diagnoses. In vitro, ABT-751 was cytotoxic at concentrations tolerable in children. Effects of ABT-751 on polymerization and microtubule structure were time- and dose-dependent but not dependent on tumor type. Pediatr Blood Cancer 2010;54:47-54. (C) 2009 Wiley-Liss, Inc. C1 [Meany, Holly J.] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. [Meany, Holly J.; Balis, Frank M.; Fox, Elizabeth] NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Ward, Yvona] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Krivoshik, Andrew] Abbott Labs, Abbott Pk, IL 60064 USA. [Cohn, Susan L.] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Meany, HJ (reprint author), Childrens Natl Med Ctr, Dept Hematol Oncol, Michigan Ave NW, Washington, DC 20010 USA. EM hmeany@cnmc.org OI Cohn, Susan/0000-0001-5749-7650 FU NIH; National Cancer Institute; Center for Cancer Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by intramural funds of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 30 TC 13 Z9 13 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2010 VL 54 IS 1 BP 47 EP 54 DI 10.1002/pbc.22267 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 525ON UT WOS:000272225800011 PM 19731320 ER PT J AU Raygada, M Arthur, DC Wayne, AS Rennert, OM Toretsky, JA Stratakis, CA AF Raygada, Margarita Arthur, Diane C. Wayne, Alan S. Rennert, Owen M. Toretsky, Jeffrey A. Stratakis, Constantine A. TI Juvenile Xanthogranuloma in a Child With Previously Unsuspected Neurofibromatosis Type 1 and Juvenile Myelomonocytic Leukemia SO PEDIATRIC BLOOD & CANCER LA English DT Article DE Cafe-au-lait spots; hepatomegaly; juvenile myelomonocytic leukemia; juvenile xanthogranuloma; neurofibromatosis 1 AB The association of neurofibromatosis 1 (NF1), juvenile xanthogranulomas (JXG), and juvenile myelomonocytic leukemia (JMML) has been previously reported. We describe herein this triad in a Caucasian male infant with a pathogenic Mutation in the NF1 gene (neurofibromin). The clinical course from initial presentation to final diagnosis is detailed; the physical features and hematologic characteristics are discussed. The patient underwent bone marrow transplantation and is currently in remission. Children with concurrent cutaneous cafe-au-lait and JXG lesions should be evaluated and monitored closely for the possible development of JMML. Pediatr Blood Cancer 2010;54:173-175. (C) 2009Wiley-Liss, Inc. C1 [Raygada, Margarita; Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Bethesda, MD 20892 USA. [Arthur, Diane C.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Wayne, Alan S.] NCI, Pediat Oncol Branch, Hatfield Clin Res Ctr 10CRC, Bethesda, MD 20892 USA. [Toretsky, Jeffrey A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Toretsky, Jeffrey A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Pediat, Washington, DC USA. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Hatfield Clin Res Ctr 10CRC, Bethesda, MD 20892 USA. RP Raygada, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, 10 Ctr Dr MSC 1831 Room 10N256, Bethesda, MD 20892 USA. EM mr346j@nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research; National Institute of Child Health and Human Development FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Grant sponsor: National Institute of Child Health and Human Development. NR 10 TC 19 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2010 VL 54 IS 1 BP 173 EP 175 DI 10.1002/pbc.22297 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 525ON UT WOS:000272225800035 PM 19785027 ER PT J AU Willson, DF Dean, JM Meert, KL Newth, CJL Anand, KJS Berger, J Harrison, R Zimmerman, J Carcillo, J Pollack, M Holubkov, R Jenkins, TL Nicholson, C AF Willson, Douglas F. Dean, J. Michael Meert, Kathleen L. Newth, Christopher J. L. Anand, Kanwaljeet J. S. Berger, John Harrison, Rick Zimmerman, Jerry Carcillo, Joseph Pollack, Murray Holubkov, Richard Jenkins, Tammara L. Nicholson, Carol CA Eunice Kennedy Shriver Natl Inst C Human Dev Collaborative Pediat Cri TI Collaborative Pediatric Critical Care Research Network: Looking back and moving forward SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE Collaborative Pediatric Critical Care Research Network; NICHD; bereavement; corticosteroids; sepsis; severity scoring systems; metoclopramide; zinc; selenium; glutamine; pertussis; opioid tolerance; withdrawal; pulmonary hypertension; decision support; weaning; cardiac arrest; hypothermia; asthma ID RANDOMIZED CONTROLLED-TRIAL; ACUTE LUNG INJURY; CORTICOSTEROID-BINDING GLOBULIN; ENRICHED ENTERAL NUTRITION; ORAL REHYDRATION THERAPY; WHOLE-BODY HYPOTHERMIA; LOW-BIRTH-WEIGHT; INTENSIVE-CARE; CARDIAC-ARREST; UNITED-STATES AB Objective. To update the pediatric critical care community on the progress of the Collaborative Pediatric Critical Care Research Network and plans for the future. Setting: The six sites, seven hospitals of the Collaborative Pediatric Critical Care Research Network. Results. From the time of its inception in August 2005, the Network has engaged in a number of observational and interventional trials, several of which are ongoing. Additional studies are in the planning stages. To date, these studies have resulted in the publication of six manuscripts and five abstracts, with five additional manuscripts accepted and in press. Conclusion: The Network remains committed to its stated goal "to initiate a multicentered program designed to investigate the safety and efficacy of treatment and management strategies to care for critically ill children, as well as the pathophysiologic basis of critical illness and injury in childhood." (Pediatr Crit Care Med 2010; 11:1-6) C1 [Willson, Douglas F.] Univ Virginia, Dept Pediat, Childrens Hosp, Charlottesville, VA 22903 USA. [Dean, J. Michael; Holubkov, Richard] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. [Meert, Kathleen L.] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA. [Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. [Anand, Kanwaljeet J. S.] Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72202 USA. [Anand, Kanwaljeet J. S.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Berger, John; Pollack, Murray] Childrens Natl Med Ctr, Dept Pediat, Charlottesville, VA USA. [Harrison, Rick] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Zimmerman, Jerry] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA. [Carcillo, Joseph] Childrens Hosp Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15213 USA. [Jenkins, Tammara L.; Nicholson, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Bethesda, MD USA. RP Willson, DF (reprint author), Univ Virginia, Dept Pediat, Childrens Hosp, Charlottesville, VA 22903 USA. EM dfw4m@virginia.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10HD050096, U10HD049981, U10HD500009, U10HD049945, U10HD049983, U10H0050012, U01HD049934]; Department of Health and Human Services FX This work was supported, in part, by cooperative agreements (U10HD050096, U10HD049981, U10HD500009, U10HD049945, U10HD049983 U10H0050012 and U01HD049934) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Department of Health and Human Services. NR 74 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JAN PY 2010 VL 11 IS 1 BP 1 EP 6 DI 10.1097/PCC.0b013e181c1302 PG 6 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 541FX UT WOS:000273401800001 PM 19794321 ER PT J AU Read, JS Samuel, NM Srijayanth, P Dharmarajan, S Van Hook, HM Jacob, M Junankar, V Bethel, J Yu, E Stoszek, SK AF Read, Jennifer S. Samuel, N. M. Srijayanth, Parameshwari Dharmarajan, Shoba Van Hook, Hannah M. Jacob, Mini Junankar, Viju Bethel, James Yu, Eunice Stoszek, Sonia K. CA PMTCT Project TI Infants of Human Immunodeficiency Virus Type 1-Infected Women in Rural South India SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE infant feeding; HIV-1; mother-to-child transmission; India ID TO-CHILD TRANSMISSION; BREAST-MILK; HIV-1 AB Background: We assessed the infant feeding choices of HIV-1-infected women in rural Tamil Nadu, India, and risk factors for mother-to-child transmission of HIV-1. Methods: The study population comprised live born infants of HIV-1-infected women from the antenatal clinics of 2 public hospitals in rural Tamil Nadu, India who were enrolled in a prospective cohort study. All women enrolled in the cohort were offered antiretroviral prophylaxis and infant feeding counseling based on WHO/UNAIDS/UNICEF training materials. Infant study visits were scheduled at birth (within the first 24 hours of life), at 1 week, 1 month, and 2 months after birth, and then every 2 months between 4 and 12 months of age. Results: One-third of women did not breast-feed their infants. Of those who initiated breast-feeding, the median duration of breast-feeding was approximately 3 months. Among those infants who initiated breast-feeding, the proportion exclusively breast-feeding declined from approximately 70% during the first week of life to 0% by the 8 month visit. The observed rate of mother-to-child transmission of HIV-1 in the entire cohort was 6.5% (95% CI: 1.4%-17.9%). The observed HIV-1 incidence among breast-fed infants was 0% (95% CI: 0%-8.9%). Conclusion: The overall transmission rate was relatively low, suggesting effectiveness of antiretroviral transmission prophylaxis. the infant feeding choices made may reflect knowledge gained through the educational program and infant feeding counseling provided. Ensuring HIV-1-infected women receive appropriate HIV-1 treatment (for those who meet criteria for treatment) and access to known efficacious interventions to prevent mother-to-child transmission of HIV-1, are essential. C1 [Read, Jennifer S.] NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. [Samuel, N. M.; Srijayanth, Parameshwari; Dharmarajan, Shoba; Jacob, Mini] Tamil Nadu Dr MGR Med Univ, Dept Expt Med, Madras, Tamil Nadu, India. [Van Hook, Hannah M.; Junankar, Viju; Bethel, James; Yu, Eunice] WESTAT Corp, Rockville, MD 20850 USA. RP Read, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11C,6100 Execut Blvd MSC 7510, Bethesda, MD 20892 USA. EM jennifer_read@nih.gov FU National Institutes of Health [N01-3-3345] FX Supported by the National Institutes of Health (NICHD Contract #N01-3-3345). NR 13 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2010 VL 29 IS 1 BP 14 EP 17 DI 10.1097/INF.0b013e3181b20ffc PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 538KT UT WOS:000273184100004 PM 19910839 ER PT J AU Ferkol, T Zeitlin, P Abman, S Blaisdell, CJ O'Brodovich, H AF Ferkol, Thomas Zeitlin, Pamela Abman, Steven Blaisdell, Carol J. O'Brodovich, Hugh TI NHLBI Training Workshop Report: The Vanishing Pediatric Pulmonary Investigator and Recommendations for Recovery SO PEDIATRIC PULMONOLOGY LA English DT Article DE clinician researcher; training pipeline ID PULMONOLOGY; FUTURE AB The adequacy of the pipeline of advanced pulmonary fellows to supply appropriately trained and committed researchers to enter academic careers was the major topic of a recently held National Heart Lung and Blood Institute NHLBI Workshop: Respiratory Medicine-Related Research Training for Adult and Pediatric Fellows. The special challenges and opportunities for the academic pediatric pulmonary trainee were discussed as part of this workshop and are discussed as a companion paper to the report by the full workshop. Surveys were conducted of pediatric chairs of academic departments and pediatric pulmonary training directors in the United States to examine the current status and opportunities for the pediatric pulmonary trainee. Strategies for recruitment and retention of talented young trainees and junior faculty are proposed. Pediatr Pulmonol. 2010; 45:25-33. (C) 2009 Wiley-Liss, Inc. C1 [Blaisdell, Carol J.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. [Ferkol, Thomas] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Zeitlin, Pamela] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. [Abman, Steven] Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA. [O'Brodovich, Hugh] Stanford Sch Med, Dept Pediat, Stanford, CA USA. RP Blaisdell, CJ (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr 10042, Bethesda, MD 20892 USA. EM blaisdellej@nhlbi.nih.gov NR 7 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD JAN PY 2010 VL 45 IS 1 BP 25 EP 33 DI 10.1002/ppul.21155 PG 9 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 544BA UT WOS:000273625000003 PM 20025052 ER PT J AU Elnitski, L AF Elnitski, Laura TI FUNCTIONAL ANALYSES OF CIS-REGULATORY ELEMENTS IN THE CFTR LOCUS AND SURROUNDING REGIONS SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Elnitski, Laura] NHGRI, Rockville, MD USA. NR 3 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 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PY 2010 SU 33 BP 183 EP 184 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 664UQ UT WOS:000282988800055 ER PT J AU Natarajan, G Shankaran, S McDonald, SA Das, A Stoll, BJ Higgins, RD Thorsen, P Skogstrand, K Hougaard, DM Carlo, WA AF Natarajan, Girija Shankaran, Seetha McDonald, Scott A. Das, Abhik Stoll, Barbara J. Higgins, Rosemary D. Thorsen, Poul Skogstrand, Kristin Hougaard, David M. Carlo, Waldemar A. CA Nichd Neonatal Res Network TI Circulating beta Chemokine and MMP 9 as Markers of Oxidative Injury in Extremely Low Birth Weight Infants SO PEDIATRIC RESEARCH LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FETAL INFLAMMATORY RESPONSE; BRONCHOPULMONARY DYSPLASIA; MATRIX METALLOPROTEINASES; PRETERM INFANTS; LUNG INFLAMMATION; TISSUE INHIBITORS; GESTATIONAL-AGE; LAVAGE FLUID; NEWBORN AB Matrix metalloproteinases (MMPs) and chemokines seem to be induced by hyperoxia in preclinical studies. We hypothesized that O(2) exposure immediately after birth is associated with altered blood spot MMP 9 and beta chemokine concentrations. The following analytes were measured on blood spots on d 1 and 3 of life, using luminex technology in 1059 infants (birth weights <1000 g) in the NICHD Neonatal Research Network: MMP 9, monocyte chemoattractant protein 1 (MCP 1), macrophage inflammatory proteins (1 alpha and beta), and regulated upon activation, normal t cell expressed and secreted (RANTES). Infants administered 0, continually from 6 to 24 h of life (n = 729), when compared with those with <6 h exposure (n = 330), had significantly lower mean birth weight and higher rate of respiratory distress syndrome (p < 0.002). On d 3, MCP 1 was higher and RANTES lower among infants with early prolonged O(2) exposure. After adjusting for covariates, prolonged early O(2) exposure retained a statistically significant association with higher MCP 1 on d 3 (p = 0.003). The consistent association between O(2) exposure and MCP I among extremely preterm infants suggests that further investigation of its role in oxidative injury is warranted. (Pediatr Res 67: 77-82, 2010) C1 [Natarajan, Girija; Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [McDonald, Scott A.] RTI Int, Stat & Epidemiol, Res Triangle Pk, NC 27709 USA. [Das, Abhik] RTI Int, Stat & Epidemiol, Rockville, MD 20852 USA. [Stoll, Barbara J.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Thorsen, Poul] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. [Thorsen, Poul] Univ Aarhus, Dept Epidemiol & Social Med, DK-8000 Aarhus, Denmark. [Skogstrand, Kristin; Hougaard, David M.] Statens Serum Inst, Dept Clin Biochem & Immunol, DK-2300 Copenhagen, Denmark. [Carlo, Waldemar A.] Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. RP Natarajan, G (reprint author), Childrens Hosp Michigan, Div Neonatol, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM gnatara@med.wayne.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Department of Health and Human Services [U10 HD21385, U10 HD40689, U10 HD27871, U10 HD21373, U10 HD36790, U10 HD40461, U10 HD34216, U10 HD21397, U10 HD27904, U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10 HD27880, U10 HD27851, R03 HD054420]; National Institutes of Health [GCRC M01 RR 08084, MW RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, 11001 RR 00039, 5 M01 RR00044] FX Supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Department of Health and Human Services Grants U10 HD21385, U10 HD40689, U10 HD27871, U10 HD21373, U10 HD36790, U10 HD40461, U10 HD34216, U10 HD21397, U10 HD27904. U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10 HD27880, U10 HD27851, and R03 HD054420 and National Institutes of Health Grants GCRC M01 RR 08084, MW RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, 11001 RR 00039, and 5 M01 RR00044. NR 41 TC 7 Z9 8 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2010 VL 67 IS 1 BP 77 EP 82 PG 6 WC Pediatrics SC Pediatrics GA 535OL UT WOS:000272980000014 PM 19755933 ER PT J AU Merikangas, KR He, JP Brody, D Fisher, PW Bourdon, K Koretz, DS AF Merikangas, Kathleen Ries He, Jian-Ping Brody, Debra Fisher, Prudence W. Bourdon, Karen Koretz, Doreen S. TI Prevalence and Treatment of Mental Disorders Among US Children in the 2001-2004 NHANES SO PEDIATRICS LA English DT Article DE mental disorders; children; epidemiology; services; National ealth and Nutrition Examination Survey ID DIAGNOSTIC INTERVIEW SCHEDULE; ADOLESCENT PSYCHIATRIC-DISORDERS; VERSION 2.3 DISC-2.3; SUPPLEMENT NCS-A; III-R DISORDERS; HEALTH-SERVICES; PUERTO-RICO; PSYCHOPATHOLOGY; EPIDEMIOLOGY; CHILDHOOD AB OBJECTIVE: This article presents the 12-month prevalence estimates of specific mental disorders, their social and demographic correlates, and service use patterns in children and adolescents from the National Health and Nutrition Examination Survey, a nationally representative probability sample of noninstitutionalized US civilians. METHODS: The sample includes 3042 participants 8 to 15 years of age from cross-sectional surveys conducted from 2001 to 2004. Data on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for mental disorders were derived from administration of selected modules of the National Institute of Mental Health Diagnostic Interview Schedule for Children, version IV, a structured diagnostic interview administered by lay interviewers to assess psychiatric diagnoses of children and adolescents. RESULTS: Twelve-month prevalence rates of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined disorders in this sample were 8.6% for attention-deficit/hyperactivity disorder, 3.7% for mood disorders, 2.1% for conduct disorder, 0.7% for panic disorder or generalized anxiety disorder, and 0.1% for eating disorders. Boys had 2.1 times greater prevalence of attention-deficit/hyperactivity disorder than girls, girls had twofold higher rates of mood disorders than boys, and there were no gender differences in the rates of anxiety disorders or conduct disorder. Only approximately one half of those with one of the disorders assessed had sought treatment with a mental health professional. CONCLUSION: These data constitute a first step in building a national database on mental health in children and adolescents. Pediatrics 2010;125:75-81 C1 [Merikangas, Kathleen Ries; He, Jian-Ping] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. [Bourdon, Karen] NIMH, Epidemiol Branch, Bethesda, MD 20892 USA. [Brody, Debra] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Fisher, Prudence W.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Koretz, Doreen S.] Harvard Univ, Off Provost, Cambridge, MA 02138 USA. RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Bldg 35,Room 1A201,35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM kathleen.merikangas@nih.gov FU Intramural NIH HHS [Z01 MH002870-02, Z01 MH002870-03, ZIA MH002870-04] NR 53 TC 288 Z9 293 U1 5 U2 43 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2010 VL 125 IS 1 BP 75 EP 81 DI 10.1542/peds.2008-2598 PG 7 WC Pediatrics SC Pediatrics GA 540PR UT WOS:000273348000010 PM 20008426 ER PT J AU Bocchini, JA Bradley, JS Brady, MT Bernstein, HH Byington, CL Fisher, MC Glode, MP Jackson, MA Keyserling, HL Kimberlin, DW Orenstein, WA Schutze, GE Willoughby, RE Bell, BP Bortolussi, R Clover, RD Fischer, MA Gorman, RL Lee, L Pratt, RD Read, JS Gellin, BG Starke, JR Swanson, J Meissner, HC Rubin, LG Pickering, LK Baker, CJ Long, SS Frantz, J AF Bocchini, Joseph A., Jr. Bradley, John S. Brady, Michael T. Bernstein, Henry H. Byington, Carrie L. Fisher, Margaret C. Glode, Mary P. Jackson, Mary Anne Keyserling, Harry L. Kimberlin, David W. Orenstein, Walter A. Schutze, Gordon E. Willoughby, Rodney E., Jr. Bell, Beth P. Bortolussi, Robert Clover, Richard D. Fischer, Marc A. Gorman, Richard L. Lee, Lucia Pratt, R. Douglas Read, Jennifer S. Gellin, Bruce G. Starke, Jeffrey R. Swanson, Jack Meissner, H. Cody Rubin, Lorry G. Pickering, Larry K. Baker, Carol J. Long, Sarah S. Frantz, Jennifer CA Comm Infect Dis TI Policy Statement-Recommended Childhood and Adolescent Immunization Schedules-United States, 2010 SO PEDIATRICS LA English DT Article C1 [Bell, Beth P.; Fischer, Marc A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Bortolussi, Robert] Canadian Paediat Soc, Ottawa, ON, Canada. [Clover, Richard D.] Amer Acad Family Phys, Leawood, KS USA. [Gorman, Richard L.] NIH, Bethesda, MD USA. [Lee, Lucia; Pratt, R. Douglas] US FDA, Rockville, MD 20857 USA. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. OI Byington, Carrie/0000-0002-7350-9495 NR 3 TC 10 Z9 11 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2010 VL 125 IS 1 BP 195 EP 196 DI 10.1542/peds.2009-3194 PG 2 WC Pediatrics SC Pediatrics GA 540PR UT WOS:000273348000027 ER PT J AU Hintz, SR Bann, CM Ambalavanan, N Cotten, M Das, A Higgins, RD AF Hintz, Susan R. Bann, Carla M. Ambalavanan, Namasivayam Cotten, Michael Das, Abhik Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst C TI Predicting Time to Hospital Discharge for Extremely Preterm Infants SO PEDIATRICS LA English DT Article DE discharge; extremely preterm infants; health service use; hospitalization; predictive testing ID BIRTH-WEIGHT INFANTS; WEEKS GESTATION; NEURODEVELOPMENTAL OUTCOMES; NECROTIZING ENTEROCOLITIS; INDOMETHACIN PROPHYLAXIS; RESOURCE USE; AGE; MORBIDITY; STAY; COST AB BACKGROUND: As extremely preterm infant mortality rates have decreased, concerns regarding resource use have intensified. Accurate models for predicting time to hospital discharge could aid in resource planning, family counseling, and stimulate quality-improvement initiatives. OBJECTIVES: To develop, validate, and compare several models for predicting the time to hospital discharge for infants <27 weeks' estimated gestational age, on the basis of time-dependent covariates as well as the presence of 5 key risk factors as predictors. PATIENTS AND METHODS: We conducted a retrospective analysis of infants <27 weeks' estimated gestational age who were born between July 2002 and December 2005 and survived to discharge from a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network site. Time to discharge was modeled as continuous (postmenstrual age at discharge) and categorical (early and late discharge) variables. Three linear and logistic regression models with time-dependent covariate inclusion were developed (perinatal factors only, perinatal + early-neonatal factors, and perinatal + early-neonatal + later factors). Models for early and late discharge that used the cumulative presence of 5 key risk factors as predictors were also evaluated. Predictive capabilities were compared by using the coefficient of determination (R(2)) for the linear models and the area under the curve (AUC) of the receiver operating characteristic curve for the logistic models. RESULTS: Data from 2254 infants were included. Prediction of postmenstrual age at discharge was poor. However, models that incorporated later clinical characteristics were more accurate in predicting early or late discharge (AUC: 0.76-0.83 [full models] vs 0.56-0.69 [perinatal factor models]). In simplified key-risk-factors models, the predicted probabilities for early and late discharge compared favorably with the observed rates. Furthermore, the AUC (0.75-0.77) was similar to those of the models that included the full factor set. CONCLUSIONS: Prediction of early or late discharge is poor if only perinatal factors are considered, but it improves substantially with knowledge of later-occurring morbidities. Predictive models that use a few key risk factors are comparable to the full models and may offer a clinically applicable strategy. Pediatrics 2010; 125: e146-e154 C1 [Hintz, Susan R.] Stanford Univ, Sch Med, Div Neonatol, Palo Alto, CA 94304 USA. [Hintz, Susan R.; Bann, Carla M.; Ambalavanan, Namasivayam; Cotten, Michael; Das, Abhik; Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Neonatal Res Network, Bethesda, MD USA. [Bann, Carla M.; Das, Abhik] Res Triangle Inst Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Ambalavanan, Namasivayam] Univ Alabama, Dept Pediat, Birmingham, AL USA. [Cotten, Michael] Duke Univ, Dept Pediat, Durham, NC 27706 USA. RP Hintz, SR (reprint author), Stanford Univ, Sch Med, Div Neonatol, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. EM srhintz@stanford.edu OI Ambalavanan, Namasivayam/0000-0003-0731-9092 FU Brown University, Women & Infants Hospital of Rhode Island [U10 HD27904]; Case Western Reserve University, Rainbow Babies & Children's Hospital [GCRC M01 RR80, U10 HD21364]; Duke University Hospital, Alamance Regional Medical Center, and Durham Regional Hospital [GCRC M01 RR30, U10 HD40492]; Children's Health Care of Atlanta, Grady Memorial Hospital, and Emory Crawford Long Hospital [GCRC M01 RR39, U10 HD27851]; Indiana University Hospital, Methodist Hospital, Riley Hospital for Children, and Wishard Health Services [GCRC M01 RR750, U10 HD27856]; CCRC; NICHD; RTI International [U01 HD36790]; Stanford University, El Camino Hospital, and Lucile Packard Children's Hospital [GCRC M01 RR70, U10 HD27880]; University of Alabama at Birmingham Health System and Children's Hospital of Alabama [GCRC M01 RR32, U10 HD34216]; Shirley S. Cosby, RN, BSN; University of California San Diego Medical Center and Sharp Mary Birch Hospital for Women [U10 HD40461]; University of Cincinnati, University Hospital, Cincinnati Children's Hospital Medical Center, and Good Samaritan Hospital [GCRC M01 RR8084, U10 HD27853]; University of Miami, Holtz Children's Hospital [GCRC M01 RR16587, U10 HD21397]; University of Rochester Medical Center and Golisano Children's Hospita [GCRC M01 RR44, U10 HD40521]; Parkland Health & Hospital System and Children's Medical Center Dallas [GCRC M01 RR633, U10 HD40689]; Children's Memorial Hermann Hospital, and Lyndon Baines Johnson General Hospital/Harris County Hospital District [U10 HD21373]; Wake Forest University Baptist Medical Center, Forsyth Medical Center, and Brenner Children's Hospital [GCRC M01 RR7122, U10 HD40498]; Wayne State University, Hutzel Women's Hospital, and Children's Hospital of Michigan [U10 HD21385]; Yale-New Haven Children's Hospital [M01 RR6022, U10 HD27871] FX Peters, RN, CCRP; Wayne State Universit, Hutzel Women's Hospital, and Children's Hospital of Michigan (U10 HD21385): Seetha Shankaran, MD, Rebecca Bara, RN, BSN, and Geraldine Muran, RN, BSN; and Yale University, Yale-New Haven Children's Hospital (GCRC M01 RR6022 and U10 HD27871): Richard A. Ehrenkranz, MD, Patricia Gettner, RN, and Monica Konstantino, RN, BSN. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. NR 28 TC 21 Z9 21 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2010 VL 125 IS 1 BP E146 EP E154 DI 10.1542/peds.2009-0810 PG 9 WC Pediatrics SC Pediatrics GA 540PR UT WOS:000273348000047 PM 20008430 ER PT J AU Schmidt, E Bak, M Kufta, C Hambrecht, T AF Schmidt, Edward Bak, Martin Kufta, Conrad Hambrecht, Terry TI On "Visual prosthesis" by Schiller and Tehovnik (2008) SO PERCEPTION LA English DT Letter ID HUMAN OCCIPITAL CORTEX; INTRACORTICAL MICROSTIMULATION; ELECTRICAL-STIMULATION; PARYLENE; BLIND C1 [Schmidt, Edward; Bak, Martin; Kufta, Conrad; Hambrecht, Terry] NIH, Bethesda, MD 20892 USA. RP Schmidt, E (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 1 U1 0 U2 1 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2010 VL 39 IS 3 BP 433 EP 435 DI 10.1068/p6467 PG 3 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 599IV UT WOS:000277905800014 PM 20465179 ER PT J AU Simon, R AF Simon, Richard TI Clinical trial designs for evaluating the medical utility of prognostic and predictive biomarkers in oncology SO PERSONALIZED MEDICINE LA English DT Review DE adaptive design; biomarker; clinical trial design; predictive; prognostic; validation ID EARLY BREAST-CANCER; COLORECTAL-CANCER; VALIDATION; ASSAY; RECURRENCE; MICROARRAY; CHALLENGES; EFFICIENCY; SIGNATURE; TAMOXIFEN AB Physicians need improved tools for selecting treatments for individual patients. Many diagnostic entities hat were traditionally viewed as individual diseases are heterogeneous in their molecular pathogenesis and treatment responsiveness. This results in the treatment of many patients with ineffective drugs, incursion of substantial medical costs for the treatment of patients who do not benefit and the conducting of large clinical trials to identify small, average treatment benefits for heterogeneous groups of patients. In oncology, new genomic technologies provide powerful tools for the selection of patients who require systemic treatment and are most (or least) likely to benefit from a molecularly targeted therapeutic. In the large amount of literature on biomarkers, there is considerable uncertainty and confusion regarding the specifics involved in the development and evaluation of prognostic and predictive biomarker diagnostics. There is a lack of appreciation that the development of drugs with companion diagnostics increases the complexity of clinical development. Adapting to the fundamental importance of tumor heterogeneity and achieving the benefits of personalized oncology for patients and healthcare costs will require paradigm changes for clinical and statistical investigators in academia, industry and regulatory agencies. In this review, I attempt to address some of these issues and provide guidance on the design of clinical trials for evaluating the clinical utility and robustness of prognostic and predictive biomarkers. C1 NCI, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, 900 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 39 TC 57 Z9 58 U1 3 U2 11 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD JAN PY 2010 VL 7 IS 1 BP 33 EP 47 DI 10.2217/PME.09.49 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 543MS UT WOS:000273582900009 PM 20383292 ER PT S AU Ferrucci, LM Cross, AJ Gunter, MJ Ahn, J Mayne, ST Ma, XM Chanock, SJ Yeager, M Graubard, BI Berndt, SI Huang, WY Hayes, RB Sinha, R AF Ferrucci, Leah M. Cross, Amanda J. Gunter, Marc J. Ahn, Jiyoung Mayne, Susan T. Ma, Xiaomei Chanock, Stephen J. Yeager, Meredith Graubard, Barry I. Berndt, Sonja I. Huang, Wen-Yi Hayes, Richard B. Sinha, Rashmi BE Simopoulous, AP Milner, JA TI Xenobiotic Metabolizing Genes, Meat-Related Exposures, and Risk of Advanced Colorectal Adenoma SO PERSONALIZED NUTRITION: TRANSLATING NUTRIGENETIC/NUTRIGENOMIC RESEARCH INTO DIETARY GUIDELINES SE World Review of Nutrition and Dietetics LA English DT Article; Book Chapter ID POLYCYCLIC AROMATIC-HYDROCARBONS; EPOXIDE HYDROLASE POLYMORPHISMS; N-NITROSO COMPOUNDS; CANCER RISK; RED MEAT; CIGARETTE-SMOKING; ACETYLTRANSFERASE GENES; ENZYME POLYMORPHISMS; HETEROCYCLIC AMINES; CYP2A6 ACTIVITY C1 [Ferrucci, Leah M.; Cross, Amanda J.; Chanock, Stephen J.; Yeager, Meredith; Graubard, Barry I.; Berndt, Sonja I.; Huang, Wen-Yi; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ferrucci, Leah M.; Mayne, Susan T.; Ma, Xiaomei] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Gunter, Marc J.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY 10461 USA. [Ahn, Jiyoung; Hayes, Richard B.] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY 10016 USA. RP Sinha, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM sinhar@mail.nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU Intramural NIH HHS; NCI NIH HHS [TU2 CA105666, TU2 CA105666-01] NR 65 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-8055-9427-1 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2010 VL 101 BP 34 EP 45 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BOY58 UT WOS:000278067400005 PM 20436251 ER PT S AU Starlard-Davenport, A Tryndyak, V Kosyk, O Ross, SR Rusyn, I Beland, FA Pogribny, IP AF Starlard-Davenport, Athena Tryndyak, Volodymyr Kosyk, Oksana Ross, Sharon R. Rusyn, Ivan Beland, Frederick A. Pogribny, Igor P. BE Simopoulous, AP Milner, JA TI Dietary Methyl Deficiency, microRNA Expression and Susceptibility to Liver Carcinogenesis SO PERSONALIZED NUTRITION: TRANSLATING NUTRIGENETIC/NUTRIGENOMIC RESEARCH INTO DIETARY GUIDELINES SE World Review of Nutrition and Dietetics LA English DT Article; Book Chapter ID HUMAN HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR; CYCLOOXYGENASE-2 EXPRESSION; GENE-EXPRESSION; BREAST-CANCER; IN-VIVO; APOPTOSIS; CELLS; ACTIVATION; MIR-122 C1 [Starlard-Davenport, Athena; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Kosyk, Oksana; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Ross, Sharon R.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI Rusyn, Ivan/S-2426-2016 FU NIEHS NIH HHS [R01 ES015241] NR 48 TC 4 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-8055-9427-1 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2010 VL 101 BP 123 EP 130 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BOY58 UT WOS:000278067400013 PM 20436259 ER PT J AU Terracciano, A AF Terracciano, Antonio TI Secular Trends and Personality: Perspectives From Longitudinal and Cross-Cultural Studies-Commentary on Trzesniewski & Donnellan (2010) SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE LA English DT Editorial Material DE personality; trust; Neuroticism; cohort effect; culture ID NATIONAL CHARACTER; AGE; TRAITS; METAANALYSIS; DEPRESSION; ANXIETY; PERIOD AB According to cross-temporal meta-analyses (Twenge, 2000, 2001), social trends over the last decades have powerfully influenced the personality profiles of children and students, with effects accounting for 20% of the variance of Neuroticism and Extraversion. However, Trzesniewski and Donnellan (2010, this issue), who examined a large and representative U.S. high-school student sample, found little evidence of secular trends. In this commentary, I emphasize the distinction between cohort and period effects and review findings from longitudinal and cross-cultural studies on the role of social trends and other cultural influences on personality traits. Analyses of adult personality scores from the Baltimore Longitudinal Study of Aging provide little support for powerful secular effects on Neuroticism and Extraversion; evidence supports a secular trend of declining trust, along with additional small effects on other facets of personality. Analyses of personality scores from around the world suggest that social and cultural differences account for about 5% of the variance on major dimensions of personality. The integration of findings from multiple perspectives provides useful insights into the role of the environment on personality traits. C1 NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP Terracciano, A (reprint author), NIA, Lab Personal & Cognit, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM terraccianoa@mail.nih.gov RI terracciano, antonio/B-1884-2008 NR 23 TC 9 Z9 9 U1 3 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1745-6916 J9 PERSPECT PSYCHOL SCI JI Perspect. Psychol. Sci. PD JAN PY 2010 VL 5 IS 1 BP 93 EP 96 DI 10.1177/1745691609357017 PG 4 WC Psychology, Multidisciplinary SC Psychology GA 556UN UT WOS:000274618500010 PM 26162067 ER PT J AU Konno, Y Moore, R Kamiya, N Negishi, M AF Konno, Yoshihiro Moore, Rick Kamiya, Nobuhiro Negishi, Masahiko TI Nuclear xenobiotic receptor PXR-null mouse exhibits hypophosphatemia and represses the Na/Pi-cotransporter SLC34A2 SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE bone mineral density; hypophosphatemia; phosphate transporter; PXR; PXR-null mouse; SLC34A2 ID PREGNANE-X-RECEPTOR; DRUG-INDUCED OSTEOMALACIA; CYP24 EXPRESSION; GENE; RICKETS; HYPERCALCIURIA; MUTATIONS; METABOLISM; HOMEOSTASIS; ACTIVATION AB Objective We previously found that the lack of nuclear xenobiotic receptor, PXR, decreases femoral bone mineral density (BMD) in Pxr(-/-) mice. Our present study aims to elucidate the inherited phenotype that correlates with the decreased BMD and to identify the PXR-regulated gene that may link with this phenotype. Methods Pxr(+/+) and Pxr(-/-) mice were used to measure the serum levels of inorganic phosphate (Pi), calcium and vitamin D(3). Real time PCR and western blots were used to determine the intestinal and renal expressions of Pi and calcium transporters and various other genes involved in bone homeostasis. Cell-based reporter and gel shift assays were performed to characterize the promoter of the identified PXR-regulated gene. Results In both Pxr(-/-) male and female mice, lumbar, sternum, and skull were all also found to have decreased their BMD values. Serum Pi levels, but not calcium levels, are attenuated in Pxr(-/-) mice, exhibiting a phenotype of hypophosphatemia. Among the members of the Na/Pi contransporter family, only the SLC34A2 mRNA and protein are repressed in Pxr(-/-) mice. PXR can directly activate the transcription of the SLC34A2 gene through an ER6 motif on its promoter. Conclusion Pxr(-/-) mice show the inherited phenotype of hypophosphatemia. The lack of PXR results in a severe repression of the Na/Pi cotransporter NaPi-IIb/Npt2b (SLC34A2), thus leading Pxr(-/-) males and females to develop a type of hypophosphatemia. Pharmacogenetics and Genomics 20:9-17 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Konno, Yoshihiro; Moore, Rick; Kamiya, Nobuhiro; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU NIH [Z01ES71005-01]; NIEHS FX Dr Hua Xu is greatly appreciated for allowing us to use her SLC34A2 antibody. The authors thank the NIEHS histology and DNA for sequencing cores. This study was supported by the Intramural Research Program (Z01ES71005-01) of the NIH and NIEHS. NR 31 TC 6 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JAN PY 2010 VL 20 IS 1 BP 9 EP 17 DI 10.1097/FPC.0b013e328333bb28 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 540CF UT WOS:000273307600002 PM 19898264 ER PT J AU Azzato, EM Chen, RA Wacholder, S Chanock, SJ Klebanoff, MA Caporaso, NE AF Azzato, Elizabeth M. Chen, Renee A. Wacholder, Sholom Chanock, Stephen J. Klebanoff, Mark A. Caporaso, Neil E. TI Maternal EPHX1 polymorphisms and risk of phenytoin-induced congenital malformations SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE congenital malformations; EPHX1; fetal hydantoin syndrome; pharmacogenetics; phenytoin ID FETAL HYDANTOIN SYNDROME; SUPEROXIDE-DISMUTASE; CYTOCHROME P4502C9; OXIDATIVE STRESS; IN-VITRO; TERATOGENICITY; EXPRESSION; EMPHASIS; CATALASE AB Objectives The teratogenic effects of the anti-epileptic drug phenytoin have been linked to genetic differences in phenytoin disposition. The goal of this study was to assess the effect of maternal genotype of functional polymorphisms in two genes involved in phenytoin metabolism, CYP2C9 (R144C, 1395L) and EPHX1 (Y113H, H139R), on the presence of major craniofacial abnormalities (CFAs) in the child. Methods We used data from the Collaborative Perinatal Project (11959-1974), a study involving 42 000 mothers and 55 000 children to assess the effect of maternal genotype. We studied 174 pregnancies in 155 women who used phenytoin throughout their pregnancy, gave birth to a live child and had available stored blood specimens suitable for DNA extraction. Results Nineteen children had CFA. In a logistic regression model adjusted for history of phenytoin use during the first trimester and maternal epilepsy (N=157 pregnancies), the maternal EPHX1 113 H [per rare allele odds ratio (OR): 2.43, 95% confidence interval (CI): 1.16-5.10, P=0.02] and 139 R (per rare allele OR: 2.33, 95% CI: 1.09-5.00, P=0.03) alleles were associated with CFAs in the child. The maternal EPHX1 Y113/H139 (common) haplotype showed a significant protective association with CFAs in the child (OR: 0.29, 95% CI: 0.12-0.68, P=0.004), when compared to other haplotypes. CYP2C9 genotype was not related to fetal endpoints. Conclusion Maternal EPHX1 genotype may be associated with risk of fetal anomalies among pregnant women taking phenytoin. Future study is required to confirm these results in larger, independent populations. Pharmacogenetics and Genomics 20:58-63 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Azzato, Elizabeth M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. [Klebanoff, Mark A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Rockville, MD 20852 USA. [Chen, Renee A.; Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,DHHS, Gaithersburg, MD USA. [Azzato, Elizabeth M.] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England. RP Azzato, EM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 7106, Rockville, MD 20852 USA. EM azzatoe2@mail.nih.gov FU NIH; NICHD; NCI; Pfizer Inc; National Cancer Institute; NIH-University of Cambridge Graduate Partnership Program FX The authors would like to thank Dr Jonathan Tyrer for his assistance in generating haplotype frequencies. This research was supported in part by the Intramural Research Program of the NIH, the NICHD and the NCI. EMA was funded through the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc. (via a grant to the Foundation for NIH from Pfizer Inc.) and is currently supported by the National Cancer Institute and the NIH-University of Cambridge Graduate Partnership Program. NR 25 TC 9 Z9 10 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JAN PY 2010 VL 20 IS 1 BP 58 EP 63 DI 10.1097/FPC.0b013e328334b6a3 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 540CF UT WOS:000273307600007 PM 19952982 ER PT J AU Sissung, TM English, BC Venzon, D Figg, WD Deeken, JF AF Sissung, Tristan M. English, Bevin C. Venzon, David Figg, William D. Deeken, John F. TI Clinical pharmacology and pharmacogenetics in a genomics era: the DMET platform SO PHARMACOGENOMICS LA English DT Review DE DMET; genome-wide association study; pharmacogenetics; pharmacokinetics; toxicity ID PLATINUM-BASED CHEMOTHERAPY; CANCER-PATIENTS; LYMPHOBLASTIC-LEUKEMIA; POLYMORPHISM PREDICTS; GENETIC POLYMORPHISMS; COLORECTAL-CANCER; PROSTATE-CANCER; BREAST-CANCER; ASSOCIATION; IRINOTECAN AB While no genome-wide pharmacogenetics study has yet been published, the field of pharmacogenetics is moving towards exploratory, large-scale analyses of the interaction between genetic variation and drug treatment. The Drug Metabolizing Enzymes and Transporters (DMET) platform offers a standardized set of 1936 variants in 225 genes related to drug absorption, distribution, metabolism and elimination that is useful to scan the genome for previously unknown associations between variation in absorption, distribution, metabolism and elimination genes and pharmacokinetic and pharmacodynamic outcomes of drug treatment. The purpose of this review is to put the DMET platform into context within the current study designs that have been used in pharmacogenetics, and to explore the role that DMET has played - and will play - in future pharmacogenetics studies. C1 [Sissung, Tristan M.; English, Bevin C.; Venzon, David; Figg, William D.] NCI, Bethesda, MD 20892 USA. [Deeken, John F.] George Washington Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20037 USA. RP Figg, WD (reprint author), NCI, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU NIH, National Cancer Institute, Bethesda, MD, USA FX Tristan Sissung, William Figg and John Deeken served as consultants for Affymetrix and reviewed the accuracy and relevance of genes and genetic variants included on the DMET Plus panel prior to its public release in 2008. Tristan Sissung and William Figg complied with NIH policy regarding compensation to federal employees. No further ongoing financial relationships exist between the authors and Affymetrix. This study was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Bethesda, MD, USA. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the US Government. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NR 54 TC 39 Z9 42 U1 1 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2010 VL 11 IS 1 BP 89 EP 103 DI 10.2217/PGS.09.154 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 544BE UT WOS:000273625400017 PM 20017675 ER PT J AU Lim, ST Airavaara, M Harvey, BK AF Lim, Seung T. Airavaara, Mikko Harvey, Brandon K. TI Viral vectors for neurotrophic factor delivery: A gene therapy approach for neurodegenerative diseases of the CNS SO PHARMACOLOGICAL RESEARCH LA English DT Review DE Neurotrophic factor; Neurodegeneration; Gene therapy; Viral vector; Adeno-associated virus; AAV; Lentivirus; Herpes virus; HSV; Adenovirus; Parkinson's disease; Alzheimer's disease; Amyotrophic lateral sclerosis; Stroke; Epilepsy; Huntington's disease; Central nervous system; Transgene; Clinical trial ID NERVE GROWTH-FACTOR; ADENOASSOCIATED VIRUS VECTORS; AMYOTROPHIC-LATERAL-SCLEROSIS; DOPAMINERGIC NEURON DEGENERATION; INTEGRATING LENTIVIRAL VECTORS; SEPTAL CHOLINERGIC NEURONS; BASAL FOREBRAIN NEURONS; PHASE-1 CLINICAL-TRIAL; RAT PARKINSON MODEL; HUNTINGTONS-DISEASE AB The clinical manifestation of most diseases of the central nervous system results from neuronal dysfunction or loss. Diseases such as stroke, epilepsy and neurodegeneration (e.g. Alzheimer's disease and Parkinson's disease) share common cellular and molecular mechanisms (e.g. oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction) that contribute to the loss of neuronal function. Neurotrophic factors (NTFs) are secreted proteins that regulate multiple aspects of neuronal development including neuronal maintenance, survival, axonal growth and synaptic plasticity. These properties of NTFs make them likely candidates for preventing neurodegeneration and promoting neuroregeneration. One approach to delivering NTFs to diseased cells is through viral vector-mediated gene delivery. Viral vectors are now routinely used as tools for studying gene function as well as developing gene-based therapies for a variety of diseases. Currently, many clinical trials using viral vectors in the nervous system are underway or completed, and seven of these trials involve NTFs for neurodegeneration. In this review, we discuss viral vector-mediated gene transfer of NTFs to treat neurodegenerative diseases of the central nervous system. Published by Elsevier Ltd. C1 [Airavaara, Mikko; Harvey, Brandon K.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Lim, Seung T.] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. RP Harvey, BK (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, BRC Suite 200,Rm 06A729,251 Bayview Blvd, Baltimore, MD 21224 USA. EM bharvey@intra.nida.nih.gov OI Airavaara, Mikko/0000-0002-2026-1609 FU Intramural Research Program at the National Institute on Drug Abuse. FX The authors thank Douglas Howard for his assistance with figure preparation and Dr. Barry Hoffer and Dr. Deon Harvey for their review of the manuscript. The preparation of this manuscript was supported by the Intramural Research Program at the National Institute on Drug Abuse. NR 195 TC 51 Z9 53 U1 2 U2 27 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD JAN PY 2010 VL 61 IS 1 BP 14 EP 26 DI 10.1016/j.phrs.2009.10.002 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 558AD UT WOS:000274711400003 PM 19840853 ER PT J AU Chapter, MC White, CM DeRidder, A Chadwick, W Martin, B Maudsley, S AF Chapter, Megan C. White, Caitlin M. DeRidder, Angela Chadwick, Wayne Martin, Bronwen Maudsley, Stuart TI Chemical modification of Class II G protein-coupled receptor ligands: Frontiers in the development of peptide analogs as neuroendocrine pharmacological therapies SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE G protein-coupled receptor; Secretin-like; Bioavailability; Pharmacotherapeutic; Instability; Modification ID CYCLASE-ACTIVATING POLYPEPTIDE; CORTICOTROPIN-RELEASING HORMONE; VASOACTIVE-INTESTINAL-PEPTIDE; GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; GENE-RELATED PEPTIDE; GROWTH-FACTOR-I; RAT ANTERIOR-PITUITARY; CENTRAL-NERVOUS-SYSTEM; POTENTIAL CLINICAL-APPLICATIONS AB Recent research and clinical data have begun to demonstrate the huge potential therapeutic importance of ligands that modulate the activity of the secretin-like, Class II, G protein-coupled receptors (GPCRs). Ligands that can modulate the activity of these Class II GPCRs may have important clinical roles in the treatment of a wide variety of conditions such as osteoporosis, diabetes, amyotrophic lateral sclerosis and autism spectrum disorders. While these receptors present important new therapeutic targets, the large glycoprotein nature of their cognate ligands poses many problems with respect to therapeutic peptidergic drug design. These native peptides often exhibit poor bioavailability, metabolic instability, poor receptor selectivity and resultant low potencies in vivo. Recently, increased attention has been paid to the structural modification of these peptides to enhance their therapeutic efficacy. Successful modification strategies have included D-amino acid substitutions, selective truncation, and fatty acid acylation of the peptide. Through these and other processes, these novel peptide ligand analogs can demonstrate enhanced receptor subtype selectivity, directed signal transduction pathway activation, resistance to proteolytic degradation, and improved systemic bioavailability. In the future, it is likely, through additional modification strategies such as addition of circulation-stabilizing transferrin moieties, that the therapeutic pharmacopeia of drugs targeted towards Class II secretin-like receptors may rival that of the Class I rhodopsin-like receptors that currently provide the majority of clinically used GPCR-based therapeutics. Currently, Class II-based drugs include synthesized analogs of vasoactive intestinal peptide for type 2 diabetes or parathyroid hormone for osteoporosis. Published by Elsevier Inc. C1 [Chapter, Megan C.; DeRidder, Angela; Chadwick, Wayne; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Biomed Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. [White, Caitlin M.] NIA, Metab Unit, Clin Invest Lab, Biomed Res Ctr, Baltimore, MD 21224 USA. [DeRidder, Angela; Martin, Bronwen] Univ Maryland, Sch Med, Baltimore, MD 21230 USA. RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Biomed Res Ctr, Neurosci Lab, Suite 100,Room 5C228,251 Bayview Blvd, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov FU NIH, National Institute on Aging FX This work was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 207 TC 24 Z9 25 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JAN PY 2010 VL 125 IS 1 BP 39 EP 54 DI 10.1016/j.pharmthera.2009.07.006 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 558VX UT WOS:000274777600004 PM 19686775 ER PT J AU Jain, L Gardner, ER Figg, WD Chernick, MS Kong, HH AF Jain, Lokesh Gardner, Erin R. Figg, William D. Chernick, Milica S. Kong, Heidi H. TI Lack of Association Between Excretion of Sorafenib in Sweat and Hand-Foot Skin Reaction SO PHARMACOTHERAPY LA English DT Article DE sorafenib; hand-foot skin reaction; hand-foot syndrome; sweat ID RENAL-CELL CARCINOMA; THERAPY AB Study Objective. To determine if excretion of sorafenib in sweat is associated with hand-foot skin reaction in patients receiving sorafenib. Design. Prospective pilot study. Setting. Outpatient clinic of a cancer research institution. Patients. Two patients who were receiving sorafenib and developed a hand-foot skin reaction of at least grade land two healthy subjects (controls). Intervention. Sweat production was stimulated in both the patients with hand-foot skin reaction and the healthy subjects by means of pilocarpine iontophoresis. Measurements and Main Results. Sweat samples were collected from the patients with hand-foot skin reaction and from the healthy subjects. Using liquid chromatography-tandem mass spectrometry, sorafenib concentrations were measured in the sweat samples. Sweat samples from the healthy subjects were spiked with known concentrations of sorafenib to determine the lower limit of quantification of the assay, which was determined to be 5 ng/ml. Sorafenib concentrations in the samples from the patients with hand-foot skin reaction were undetectable based on the assay's sensitivity. Conclusion. Our results suggest that hand-foot skin reaction in patients receiving sorafenib is not associated with excretion of sorafenib in sweat. Further studies are needed to understand the mechanism of hand-foot skin reaction, a treatment-limiting adverse effect of multikinase inhibitors. C1 [Jain, Lokesh; Figg, William D.] NIH, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Kong, Heidi H.] NIH, Dermatol Branch, Bethesda, MD 20892 USA. [Chernick, Milica S.] NIDDKD, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chernick, Milica S.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI, Clin Pharmacol Program, Sci Applicat Int Corp, Frederick, MD 21701 USA. RP Kong, HH (reprint author), NCI, 10 Ctr Dr,Bldg 10,Room 12N238, Bethesda, MD 20892 USA. EM konghe@mail.nih.gov RI Figg Sr, William/M-2411-2016; OI Kong, Heidi/0000-0003-4424-064X FU Intramural Research Program; National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; U.S. Department of Health and Human Services; National Cancer Institute [N01-C0-12400] FX Supported by the Intramural Research Program, National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services. Partially funded by National Cancer Institute contract N01-C0-12400 (Dr. Gardner). NR 14 TC 17 Z9 17 U1 1 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JAN PY 2010 VL 30 IS 1 BP 52 EP 56 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 542DJ UT WOS:000273471400007 PM 20030473 ER PT J AU Wielgus, AR Collier, RJ Martin, E Lih, FB Tomer, KB Chignell, CF Roberts, JE AF Wielgus, A. R. Collier, R. J. Martin, E. Lih, F. B. Tomer, K. B. Chignell, C. F. Roberts, J. E. TI Blue light induced A2E oxidation in rat eyes - experimental animal model of dry AMD SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID PIGMENT EPITHELIAL-CELLS; AGE-RELATED MACULOPATHY; HUMAN RETINAL LIPOFUSCIN; SINGLET-OXYGEN GENERATION; BEAVER DAM EYE; MACULAR DEGENERATION; BRUCHS MEMBRANE; A2E-LADEN RPE; AGING RETINA; RISK-FACTORS AB Previous studies have shown that short-wavelength blue visible light induces retinal injury and may be a risk factor for age related macular degeneration. A2E is a blue light absorbing retinal chromophore that accumulates with age. Our previous in vitro studies have determined that, although A2E itself has a low phototoxic efficiency, the oxidation products of A2E that are formed in the presence of visible light can contribute to observed retinal pigment epithelial photodamage. The purpose of this study was to investigate the effects of blue light on retinal phototoxicity and its relationship to A2E, oxidized A2E and its isomers. Sprague-Dawley albino rats were dark adapted for 24 h. Control rats remained in the dark while experimental rats were exposed to blue light (lambda = 450 nm, 3.1 mW cm(-2)) for 6 h. Isolated retinas were homogenized in Folch extraction mixture and then in chloroform. The dried extracts were reconstituted and divided for determination of organic soluble compound. Esters of fatty acids were determined with GC-MS, A2E and other chromophores using HPLC, and A2E oxidation products with LC-MS. Exposure of rat eyes to blue light did not significantly change the fatty acid composition of the retina. The A2E concentration (normalized to fatty acid content) in blue light exposed animals was found to be lower than the A2E concentration in control rats. The concentrations of all-trans-retinal-ethanolamine adduct and iso-A2E a precursor and an isomer of A2E respectively, were also lower after blue-light exposure than in the retinas of rats housed in the dark. On the other hand, the amount of oxidized forms of A2E was higher in the animals exposed to blue light. We conclude that in the rat eye, blue-light exposure promotes oxidation of A2E and iso-A2E to the products that are toxic to retinal tissue. Although high concentrations of A2E may be cytotoxic to the retina, the phototoxicity associated with blue light damage to the retina is in part a result of the formation of toxic A2E oxides. This effect may partially explain the association between blue light induced retinal injury and macular degeneration. C1 [Wielgus, A. R.; Chignell, C. F.] Natl Inst Environm Hlth Sci, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. [Collier, R. J.; Martin, E.] Alcon Res Ltd, Retinopathy Degenerat Dis Res Unit, Ft Worth, TX 76134 USA. [Lih, F. B.; Tomer, K. B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Roberts, J. E.] Fordham Univ, Dept Nat Sci, New York, NY 10023 USA. RP Wielgus, AR (reprint author), Natl Inst Environm Hlth Sci, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. EM albert.wielgus@duke.edu; jroberts@fordham.edu RI Tomer, Kenneth/E-8018-2013 FU NIH, National Institute of Environmental Health Sciences [Z01 ES050167]; Alcon Research Grant FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ARW), Z01 ES050167 (KBT) and partially by an Alcon Research Grant (JER). NR 72 TC 34 Z9 38 U1 1 U2 14 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2010 VL 9 IS 11 BP 1505 EP 1512 DI 10.1039/c0pp00133c PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 672QX UT WOS:000283603100012 PM 20922251 ER PT J AU Thurber, KR Tycko, R AF Thurber, Kent R. Tycko, Robert TI Prospects for sub-micron solid state nuclear magnetic resonance imaging with low-temperature dynamic nuclear polarization SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID HIGH-RESOLUTION NMR; C-13 NMR; FIELD; DNP AB We evaluate the feasibility of 1 H nuclear magnetic resonance (NMR) imaging with sub-micron voxel dimensions using a combination of low temperatures and dynamic nuclear polarization (DNP). Experiments are performed on nitroxide-doped glycerol-water at 9.4 T and temperatures below 40 K, using a 30 mW tunable microwave source for DNP. With DNP at 7 K, a 0.5 mu L sample yields a (1)H NMR signal-to-noise ratio of 770 in two scans with pulsed spin-lock detection and after 80 db signal attenuation. With reasonable extrapolations, we infer that (1)H NMR signals from 1 mu m(3) voxel volumes should be readily detectable, and voxels as small as 0.03 mu m(3) may eventually be detectable. Through homonuclear decoupling with a frequency-switched Lee-Goldburg spin echo technique, we obtain 830 Hz (1)H NMR linewidths at low temperatures, implying that pulsed field gradients equal to 0.4 G/d or less would be required during spatial encoding dimensions of an imaging sequence, where d is the resolution in each dimension. C1 [Thurber, Kent R.; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and by the Intramural AIDS Targeted Antiviral Program of the National Institutes of Health. NR 20 TC 12 Z9 12 U1 1 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2010 VL 12 IS 22 BP 5779 EP 5785 DI 10.1039/c0cp00157k PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 601WZ UT WOS:000278098900007 PM 20458431 ER PT J AU Uetrecht, C Watts, NR Stahl, SJ Wingfield, PT Steven, AC Heck, AJR AF Uetrecht, Charlotte Watts, Norman R. Stahl, Stephen J. Wingfield, Paul T. Steven, Alasdair C. Heck, Albert J. R. TI Subunit exchange rates in Hepatitis B virus capsids are geometry- and temperature-dependent SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID MASS-SPECTROMETRY; CORE PROTEIN; STABILITY; NEUTRALIZATION; ANTIBODIES; TERMINUS; VP4 AB Native tandem mass spectrometry reveals marked differences in the rates at which the two polymorphic forms of the HBV capsid exchange dimeric subunits with the soluble pool. C1 [Uetrecht, Charlotte; Heck, Albert J. R.] Univ Utrecht, Biomol Mass Spectrometry & Prote Grp, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands. [Uetrecht, Charlotte; Heck, Albert J. R.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands. [Watts, Norman R.; Stahl, Stephen J.; 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. [Uetrecht, Charlotte; Heck, Albert J. R.] Netherlands Prote Ctr, NL-3584 CH Utrecht, Netherlands. RP Heck, AJR (reprint author), Univ Utrecht, Biomol Mass Spectrometry & Prote Grp, Bijvoet Ctr Biomol Res, Padualaan 8, NL-3584 CH Utrecht, Netherlands. EM A.J.R.Heck@uu.nl RI Heck, Albert/D-7098-2011; Uetrecht, Charlotte/D-1883-2010 OI Heck, Albert/0000-0002-2405-4404; Uetrecht, Charlotte/0000-0002-1991-7922 FU Netherlands Proteomics Centre; National Institute of Arthritis and Musculoskeletal and Skin Diseases FX We thank Ira Palmer and Joshua Kaufman for preparation of the proteins, and Klaus H. P. Gast and R. Seckler at the Physical Biochemistry Department of Potsdam University, Germany, for performing the dynamic light scattering and circular dichroism experiments. This work was supported by the Netherlands Proteomics Centre and by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 20 TC 25 Z9 25 U1 0 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2010 VL 12 IS 41 BP 13368 EP 13371 DI 10.1039/c0cp00692k PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 664OT UT WOS:000282972400002 PM 20676421 ER PT J AU Rokic, MB Tvrdonova, V Vavra, V Jindrichova, M Obsil, T Stojilkovic, SS Zemkova, H AF Rokic, M. B. Tvrdonova, V. Vavra, V. Jindrichova, M. Obsil, T. Stojilkovic, S. S. Zemkova, H. TI Roles of Conserved Ectodomain Cysteines of the Rat P2X4 Purinoreceptor in Agonist Binding and Channel Gating SO PHYSIOLOGICAL RESEARCH LA English DT Article DE Purinergic signaling; ATP-gated receptor-channels; Disulfide bonds; Ivermectin; Deactivation ID HUMAN P2X(1) RECEPTORS; CELL-SURFACE; AMINO-ACIDS; ATP-BINDING; RESIDUES; IDENTIFICATION; IVERMECTIN; DETERMINANTS; FACILITATION; MECHANISM AB Mammalian P2X receptors contain 10 conserved cysteine residues in their ectodomains, which form five disulfide bonds (SS1-5). Here, we analyzed the relevance of these disulfide pairs in rat P2X4 receptor function by replacing one or both cysteines with alanine or threonine, expressing receptors in HEK293 cells and studying their responsiveness to ATP in the absence and presence of ivermectin, an allostenic modulator of these channels. Response to ATP was not altered when both cysteines forming the SS3 bond (C132-C159) were replaced with threonines. Replacement of SS1 (C116-C165), SS2 (C126-C149) and SS4 (C217-C227), but not SS5 (C261-C270), cysteine pairs with threonines resulted in decreased sensitivity to ATP and faster deactivation times. The maximum current amplitude was reduced in SS2, SS4 and SS5 double mutants and could be partially rescued by ivermectin in SS2 and SS5 double mutants. This response pattern was also observed in numerous single residue mutants, but receptor function was not affected when the 217 cysteine was replaced with threonine or arginine or when the 261 cysteine was replaced with alanine. These results suggest that the SS1, SS2 and SS4 bonds contribute substantially to the structure of the ligand binding pocket, while the SS5 bond located towards the transmembrane domain contributes to receptor gating. C1 [Rokic, M. B.; Tvrdonova, V.; Vavra, V.; Jindrichova, M.; Zemkova, H.] Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Prague, Czech Republic. [Obsil, T.] Charles Univ Prague, Fac Sci, Dept Phys & Macromol Chem, Prague, Czech Republic. [Stojilkovic, S. S.] NICHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD USA. RP Zemkova, H (reprint author), Acad Sci Czech Republ VVI, Inst Physiol, Videnska 1083, Prague 14220 4, Czech Republic. EM zemkova@biomed.cas.cz RI Vavra, Vojtech/C-1857-2012; Zemkova, Hana/C-1844-2012; Jindrichova, Marie/C-3401-2012; Obsil, Tomas/B-7142-2012; Tvrdonova Stillerova, Vendula/G-3060-2014; Jindrichova, Marie/H-4320-2014; ROKIC, MILOS/O-7204-2014 OI Obsil, Tomas/0000-0003-4602-1272; Tvrdonova Stillerova, Vendula/0000-0001-5295-2837; ROKIC, MILOS/0000-0002-9148-2716 FU Internal Grant Agency of Academy of Sciences [IAA500110910]; Grant Agency of the Czech Republic [305/07/0681]; Academy of Sciences of the Czech Republic [AVOZ 50110509]; Centrum for Neuroscience [LC554]; NICHD, NIH FX This study was supported by the Internal Grant Agency of Academy of Sciences (Grants No. IAA500110910), the Grant Agency of the Czech Republic (305/07/0681), the Academy of Sciences of the Czech Republic (Research Project No. AVOZ 50110509), the Centrum for Neuroscience (Research Project No. LC554) and the Intramural Research Program of the NICHD, NIH. NR 25 TC 11 Z9 14 U1 0 U2 2 PU ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY PI PRAGUE 4 PA VIDENSKA 1083, PRAGUE 4 142 20, CZECH REPUBLIC SN 0862-8408 J9 PHYSIOL RES JI Physiol. Res. PY 2010 VL 59 IS 6 BP 927 EP 935 PG 9 WC Physiology SC Physiology GA 700CW UT WOS:000285711400010 PM 20406028 ER PT S AU Iyer-Pascuzzi, AS Benfey, PN AF Iyer-Pascuzzi, Anjali S. Benfey, Philip N. BE Hennig, L Kohler, C TI Fluorescence-Activated Cell Sorting in Plant Developmental Biology SO PLANT DEVELOPMENTAL BIOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Cell sorting; GFP; FAGS; cell-type specific gene expression; root; Arabidopsis ID GENE-EXPRESSION; ROOT; MAP AB Understanding the development of an organ requires knowledge of gene, protein, and metabolite expression in the specific cell types and tissues that comprise the organ. Fluorescence-activated cell sorting (FAGS) is an efficient method to isolate specific cells of interest, and the information gained from this approach has been integral to plant developmental biology. The Benfey lab has developed this method to examine gene expression profiles of different cell types in the Arabidopsis root under both standard and stress conditions. In addition to gene expression, downstream applications of FAGS include proteomic and metabolite analysis. This is a powerful method to examine biological functions of specific cell types and tissues with a systems biology approach. C1 [Iyer-Pascuzzi, Anjali S.; Benfey, Philip N.] Duke Univ, Ctr Syst Biol, NIH, Durham, NC 27710 USA. [Iyer-Pascuzzi, Anjali S.; Benfey, Philip N.] Duke Univ, Dept Biol, Durham, NC USA. RP Iyer-Pascuzzi, AS (reprint author), Duke Univ, Ctr Syst Biol, NIH, Durham, NC 27710 USA. NR 7 TC 15 Z9 15 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-764-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 655 BP 313 EP 319 DI 10.1007/978-1-60761-765-5_21 D2 10.1007/978-1-60761-765-5 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQJ66 UT WOS:000281181000021 PM 20734270 ER PT J AU Pomeranz, MC Hah, C Lin, PC Kang, SG Finer, JJ Blackshear, PJ Jang, JC AF Pomeranz, Marcelo C. Hah, Cyrus Lin, Pei-Chi Kang, Shin Gene Finer, John J. Blackshear, Perry J. Jang, Jyan-Chyun TI The Arabidopsis Tandem Zinc Finger Protein AtTZF1 Traffics between the Nucleus and Cytoplasmic Foci and Binds Both DNA and RNA SO PLANT PHYSIOLOGY LA English DT Article ID AGROBACTERIUM-MEDIATED TRANSFORMATION; 3' UNTRANSLATED REGION; GENOME-WIDE ANALYSIS; HEAT-SHOCK GRANULES; AU-RICH ELEMENTS; MESSENGER-RNA; PROCESSING BODIES; P-BODIES; METHYL JASMONATE; STRESS GRANULES AB Processing bodies (PBs) are specialized cytoplasmic foci where mRNA turnover and translational repression can take place. Stress granules are related cytoplasmic foci. The CCCH tandem zinc finger proteins (TZFs) play pivotal roles in gene expression, cell fate specification, and various developmental processes. Human TZF binds AU-rich elements at the 3' untranslated region and recruits decapping, deadenylation, and exonucleolytic enzymes to PBs for RNA turnover. Recent genetic studies indicate that plant TZFs are involved in gene regulation and hormone-mediated environmental responses. It is unknown if plant TZFs can bind RNA and be localized to PBs or stress granules. The Arabidopsis (Arabidopsis thaliana) AtTZF1/AtCTH/AtC3H23 was identified as a sugar-sensitive gene in a previous microarray study. It is characterized by a TZF motif that is distinct from the human TZF. Higher plants such as Arabidopsis and rice (Oryza sativa) each have a gene family containing this unique TZF motif. Here, we show that AtTZF1 can traffic between the nucleus and cytoplasmic foci. AtTZF1 colocalizes with markers of PBs, and the morphology of these cytoplasmic foci resembles that of mammalian PBs and stress granules. AtTZF1-associated cytoplasmic foci are dynamic and tissue specific. They can be induced by dark and wound stresses and are preferentially present in actively growing tissues and stomatal precursor cells. Since AtTZF1 can bind both DNA and RNA in vitro, it raises the possibility that AtTZF1 might be involved in DNA and/or RNA regulation. C1 [Pomeranz, Marcelo C.; Hah, Cyrus; Kang, Shin Gene; Finer, John J.; Jang, Jyan-Chyun] Ohio State Univ, Dept Hort & Crop Sci, Columbus, OH 43210 USA. [Pomeranz, Marcelo C.; Hah, Cyrus; Lin, Pei-Chi; Kang, Shin Gene; Jang, Jyan-Chyun] Ohio State Univ, Ctr Plant Biotechnol, Columbus, OH 43210 USA. [Lin, Pei-Chi; Jang, Jyan-Chyun] Ohio State Univ, Dept Plant Cellular & Mol Biol, Columbus, OH 43210 USA. [Finer, John J.] Ohio State Univ, Ohio Agr Res & Dev Ctr, Wooster, OH 44691 USA. [Blackshear, Perry J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Durham, NC 27710 USA. RP Jang, JC (reprint author), Ohio State Univ, Dept Hort & Crop Sci, Columbus, OH 43210 USA. EM jang.40@osu.edu RI Finer, John/N-4713-2014 OI Finer, John/0000-0001-8004-5468 FU National Science Foundation [IOB-0543751] FX This work was supported by the National Science Foundation (grant no. IOB-0543751 to J.-C.J.). NR 94 TC 68 Z9 71 U1 2 U2 19 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JAN PY 2010 VL 152 IS 1 BP 151 EP 165 DI 10.1104/pp.109.145656 PG 15 WC Plant Sciences SC Plant Sciences GA 537XQ UT WOS:000273148100012 PM 19897605 ER PT J AU Narendra, DP Jin, SM Tanaka, A Suen, DF Gautier, CA Shen, J Cookson, MR Youle, RJ AF Narendra, Derek P. Jin, Seok Min Tanaka, Atsushi Suen, Der-Fen Gautier, Clement A. Shen, Jie Cookson, Mark R. Youle, Richard J. TI PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin SO PLOS BIOLOGY LA English DT Article ID SUBSTANTIA-NIGRA NEURONS; LOSS-OF-FUNCTION; SUBCELLULAR-LOCALIZATION; RECESSIVE PARKINSONISM; OXIDATIVE STRESS; PROTECTS NEURONS; DNA DELETIONS; CELL-DEATH; COMPLEX-I; DISEASE AB Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown. Here, we show that expression of PINK1 on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels of PINK1 on healthy, polarized mitochondria, while facilitating the rapid accumulation of PINK1 on mitochondria that sustain damage. PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 and Parkin disrupt Parkin recruitment and Parkin-induced mitophagy at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila melanogaster. In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination. C1 [Narendra, Derek P.; Jin, Seok Min; Tanaka, Atsushi; Suen, Der-Fen; Youle, Richard J.] Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD USA. [Gautier, Clement A.; Shen, Jie] Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Program Neurosci,Sch Med, Boston, MA 02115 USA. [Cookson, Mark R.] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. RP Narendra, DP (reprint author), Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD USA. EM youler@ninds.nih.gov FU National Institutes of Health (NIH); JSPS [R01NS41779] FX This work was supported by a National Institutes of Health (NIH)-Cambridge scholarship (to DPN), a JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers (to AT), NIH grant R01NS41779 (to JS), and the intramural research program at the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 59 TC 860 Z9 876 U1 30 U2 115 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2010 VL 8 IS 1 AR e1000298 DI 10.1371/journal.pbio.1000298 PG 21 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 564ZH UT WOS:000275256800011 PM 20126261 ER PT J AU Thiagarajan, TC Lebedev, MA Nicolelis, MA Plenz, D AF Thiagarajan, Tara C. Lebedev, Mikhail A. Nicolelis, Miguel A. Plenz, Dietmar TI Coherence Potentials: Loss-Less, All-or-None Network Events in the Cortex SO PLOS BIOLOGY LA English DT Article ID LOCAL-FIELD POTENTIALS; NEURONS IN-VIVO; PRIMARY VISUAL-CORTEX; PRIMATE MOTOR CORTEX; CAT CEREBRAL-CORTEX; CORTICAL-NEURONS; COINCIDENCE DETECTION; SENSORIMOTOR CORTEX; PROPAGATING WAVES; PARIETAL CORTEX AB Transient associations among neurons are thought to underlie memory and behavior. However, little is known about how such associations occur or how they can be identified. Here we recorded ongoing local field potential (LFP) activity at multiple sites within the cortex of awake monkeys and organotypic cultures of cortex. We show that when the composite activity of a local neuronal group exceeds a threshold, its activity pattern, as reflected in the LFP, occurs without distortion at other cortex sites via fast synaptic transmission. These large-amplitude LFPs, which we call coherence potentials, extend up to hundreds of milliseconds and mark periods of loss-less spread of temporal and amplitude information much like action potentials at the single-cell level. However, coherence potentials have an additional degree of freedom in the diversity of their waveforms, which provides a high-dimensional parameter for encoding information and allows identification of particular associations. Such nonlinear behavior is analogous to the spread of ideas and behaviors in social networks. C1 [Thiagarajan, Tara C.; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Lebedev, Mikhail A.; Nicolelis, Miguel A.] Duke Univ, Dept Neurobiol, Ctr Neuroengn, Durham, NC USA. RP Thiagarajan, TC (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. EM plenzd@mail.nih.gov RI Lebedev, Mikhail/H-5066-2016 OI Lebedev, Mikhail/0000-0003-0355-8723 FU Division of Intramural Research Program of the National Institute of Mental Health, National Institutes of Health; Defense Advanced Research Projects Agency (DARPA) FX TCT and DP were supported by the Division of Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. MAL and MAN were supported by Defense Advanced Research Projects Agency (DARPA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 81 TC 24 Z9 24 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2010 VL 8 IS 1 AR e1000278 DI 10.1371/journal.pbio.1000278 PG 18 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 564ZH UT WOS:000275256800007 PM 20084093 ER PT J AU Dickson, J Gowher, H Strogantsev, R Gaszner, M Hair, A Felsenfeld, G West, AG AF Dickson, Jacqueline Gowher, Humaira Strogantsev, Ruslan Gaszner, Miklos Hair, Alan Felsenfeld, Gary West, Adam G. TI VEZF1 Elements Mediate Protection from DNA Methylation SO PLOS GENETICS LA English DT Article ID BETA-GLOBIN INSULATOR; ZINC-FINGER PROTEIN; CPG ISLAND; EPIGENETIC MODIFICATIONS; TRANSCRIPTION FACTOR; ENHANCER BLOCKING; GENE PROMOTER; HUMAN GENOME; CHROMATIN; BARRIER AB There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm beta-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin state. C1 [Dickson, Jacqueline; Strogantsev, Ruslan; Hair, Alan; West, Adam G.] Univ Glasgow, Western Infirm, Fac Med, Sect Pathol & Gene Regulat, Glasgow G11 6NT, Lanark, Scotland. [Gowher, Humaira; Gaszner, Miklos; Felsenfeld, Gary; West, Adam G.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dickson, J (reprint author), Univ Glasgow, Western Infirm, Fac Med, Sect Pathol & Gene Regulat, Glasgow G11 6NT, Lanark, Scotland. EM gary.felsenfeld@nih.gov; a.west@clinmed.gla.ac.uk OI West, Adam/0000-0003-3502-7804 FU Association for International Cancer Research [05-433]; European Commission [MIRG-CT-2004-006684]; UK Medical Research Council [G0400180]; NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by grants from the Association for International Cancer Research (05-433), the European Commission (MIRG-CT-2004-006684), the UK Medical Research Council (G0400180), and the intramural research program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 58 Z9 60 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2010 VL 6 IS 1 AR e1000804 DI 10.1371/journal.pgen.1000804 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 551GF UT WOS:000274194300012 PM 20062523 ER PT J AU Haugen, AC Di Prospero, NA Parker, JS Fannin, RD Chou, J Meyer, JN Halweg, C Collins, JB Durr, A Fischbeck, K Van Houten, B AF Haugen, Astrid C. Di Prospero, Nicholas A. Parker, Joel S. Fannin, Rick D. Chou, Jeff Meyer, Joel N. Halweg, Christopher Collins, Jennifer B. Durr, Alexandra Fischbeck, Kenneth Van Houten, Bennett TI Altered Gene Expression and DNA Damage in Peripheral Blood Cells from Friedreich's Ataxia Patients: Cellular Model of Pathology SO PLOS GENETICS LA English DT Article ID TRIPLET-REPEAT EXPANSION; IRON-SULFUR CLUSTERS; OXIDATIVE STRESS; IN-VIVO; HYDROGEN-PEROXIDE; MITOCHONDRIAL; FRATAXIN; PROTEINS; CARDIOMYOPATHY; TRANSCRIPTION AB The neurodegenerative disease Friedreich's ataxia ( FRDA) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene. In this disease, transcription of frataxin, a mitochondrial protein involved in iron homeostasis, is impaired, resulting in a significant reduction in mRNA and protein levels. Global gene expression analysis was performed in peripheral blood samples from FRDA patients as compared to controls, which suggested altered expression patterns pertaining to genotoxic stress. We then confirmed the presence of genotoxic DNA damage by using a gene-specific quantitative PCR assay and discovered an increase in both mitochondrial and nuclear DNA damage in the blood of these patients (p<0.0001, respectively). Additionally, frataxin mRNA levels correlated with age of onset of disease and displayed unique sets of gene alterations involved in immune response, oxidative phosphorylation, and protein synthesis. Many of the key pathways observed by transcription profiling were downregulated, and we believe these data suggest that patients with prolonged frataxin deficiency undergo a systemic survival response to chronic genotoxic stress and consequent DNA damage detectable in blood. In conclusion, our results yield insight into the nature and progression of FRDA, as well as possible therapeutic approaches. Furthermore, the identification of potential biomarkers, including the DNA damage found in peripheral blood, may have predictive value in future clinical trials. C1 [Haugen, Astrid C.; Halweg, Christopher] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Di Prospero, Nicholas A.; Fischbeck, Kenneth] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. [Parker, Joel S.] Express Anal, Durham, NC USA. [Fannin, Rick D.; Chou, Jeff; Collins, Jennifer B.] NIEHS, Lab Toxicogen, Res Triangle Pk, NC 27709 USA. [Meyer, Joel N.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. [Durr, Alexandra] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Paris, France. [Durr, Alexandra] Hop La Pitie Salpetriere, Dept Genet & Embryol, Paris, France. [Van Houten, Bennett] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Van Houten, Bennett] Univ Pittsburgh, Hillman Canc Ctr, Univ Pittsburgh Canc Inst, Pittsburgh, PA USA. RP Haugen, AC (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. EM vanhoutenb@upmc.edu FU NIH FX This work was supported by a Bench to Bedside award by the Office of Rare Diseases, NIH, to BVH. Some of this work was supported by NIH intramural research to KF, NADP, and BVH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 70 TC 39 Z9 40 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2010 VL 6 IS 1 AR e1000812 DI 10.1371/journal.pgen.1000812 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 551GF UT WOS:000274194300020 PM 20090835 ER PT J AU Khil, PP Camerini-Otero, RD AF Khil, Pavel P. Camerini-Otero, R. Daniel TI Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map SO PLOS GENETICS LA English DT Article ID CLASS-II REGION; MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN MEIOTIC RECOMBINATION; HOTSPOT CONVERSION PARADOX; HUMAN GENOME; LINKAGE DISEQUILIBRIUM; HOT-SPOTS; MARKER ASSOCIATION; POPULATION HISTORY; HAPLOTYPE MAP AB Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers. C1 [Khil, Pavel P.; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Khil, PP (reprint author), NIDDK, Genet & Biochem Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM camerini@ncifcrf.gov RI Sincan, Murat /A-3794-2010; OI Khil, Pavel/0000-0002-4903-8777 FU NIDDK FX This research was supported by the NIDDK Intramural Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 66 TC 13 Z9 13 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2010 VL 6 IS 1 AR e1000831 DI 10.1371/journal.pgen.1000831 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 551GF UT WOS:000274194300037 PM 20126534 ER PT J AU Nakamura, K Kogame, T Oshiumi, H Shinohara, A Sumitomo, Y Agama, K Pommier, Y Tsutsui, KM Tsutsui, K Hartsuiker, E Ogi, T Takeda, S Taniguchi, Y AF Nakamura, Kyoko Kogame, Toshiaki Oshiumi, Hiroyuki Shinohara, Akira Sumitomo, Yoshiki Agama, Keli Pommier, Yves Tsutsui, Kimiko M. Tsutsui, Ken Hartsuiker, Edgar Ogi, Tomoo Takeda, Shunichi Taniguchi, Yoshihito TI Collaborative Action of Brca1 and CtIP in Elimination of Covalent Modifications from Double-Strand Breaks to Facilitate Subsequent Break Repair SO PLOS GENETICS LA English DT Article ID DNA-END RESECTION; SUSCEPTIBILITY GENE BRCA1; HOMOLOGOUS RECOMBINATION; VERTEBRATE CELLS; TOPOISOMERASE-I; SACCHAROMYCES-CEREVISIAE; IONIZING-RADIATION; DAMAGE RESPONSE; COMPLEX; PROTEIN AB Topoisomerase inhibitors such as camptothecin and etoposide are used as anti-cancer drugs and induce double-strand breaks (DSBs) in genomic DNA in cycling cells. These DSBs are often covalently bound with polypeptides at the 3' and 5' ends. Such modifications must be eliminated before DSB repair can take place, but it remains elusive which nucleases are involved in this process. Previous studies show that CtIP plays a critical role in the generation of 3' single-strand overhang at "clean" DSBs, thus initiating homologous recombination (HR)-dependent DSB repair. To analyze the function of CtIP in detail, we conditionally disrupted the CtIP gene in the chicken DT40 cell line. We found that CtIP is essential for cellular proliferation as well as for the formation of 3' single-strand overhang, similar to what is observed in DT40 cells deficient in the Mre11/Rad50/Nbs1 complex. We also generated DT40 cell line harboring CtIP with an alanine substitution at residue Ser332, which is required for interaction with BRCA1. Although the resulting CtIP(S332A/-/-) cells exhibited accumulation of RPA and Rad51 upon DNA damage, and were proficient in HR, they showed a marked hypersensitivity to camptothecin and etoposide in comparison with CtIP(+/-/-) cells. Finally, CtIP(S332A/-/-)BRCA1(-/-) and CtIP(+/-/-)BRCA1(-/-) showed similar sensitivities to these reagents. Taken together, our data indicate that, in addition to its function in HR, CtIP plays a role in cellular tolerance to topoisomerase inhibitors. We propose that the BRCA1-CtIP complex plays a role in the nuclease-mediated elimination of oligonucleotides covalently bound to polypeptides from DSBs, thereby facilitating subsequent DSB repair. C1 [Nakamura, Kyoko; Kogame, Toshiaki; Sumitomo, Yoshiki; Takeda, Shunichi; Taniguchi, Yoshihito] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Kyoto, Japan. [Oshiumi, Hiroyuki; Shinohara, Akira] Osaka Univ, Grad Sch Sci, Inst Prot Res, Osaka, Japan. [Agama, Keli; Pommier, Yves] NCI, Mol Pharmacol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Tsutsui, Kimiko M.; Tsutsui, Ken] Okayama Univ, Dept Neurogenom, Dept Genome Dynam, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan. [Hartsuiker, Edgar] Bangor Univ, NW Canc Res Fund Inst, Bangor, Gwynedd, Wales. [Ogi, Tomoo] Nagasaki Univ, Atom Bomb Dis Inst, Dept Mol Med, Nagasaki 852, Japan. RP Nakamura, K (reprint author), Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Kyoto, Japan. EM taniguchi@rg.med.kyoto-u.ac.jp RI OSHIUMI, HIROYUKI/G-1645-2012; Nakamura, Kyoko/B-4184-2013; Taniguchi, Yoshihito/L-5746-2013; OI Ogi, Tomoo/0000-0002-5492-9072 FU Japanese Promoting Science and Technology [17013039] FX This work was supported by the grants from the Japanese Promoting Science and Technology (17013039). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 40 Z9 41 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2010 VL 6 IS 1 AR e1000828 DI 10.1371/journal.pgen.1000828 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 551GF UT WOS:000274194300034 PM 20107609 ER PT J AU Klatt, NR Shudo, E Ortiz, AM Engram, JC Paiardini, M Lawson, B Miller, MD Else, J Pandrea, I Estes, JD Apetrei, C Schmitz, JE Ribeiro, RM Perelson, AS Silvestri, G AF Klatt, Nichole R. Shudo, Emi Ortiz, Alex M. Engram, Jessica C. Paiardini, Mirko Lawson, Benton Miller, Michael D. Else, James Pandrea, Ivona Estes, Jacob D. Apetrei, Cristian Schmitz, Joern E. Ribeiro, Ruy M. Perelson, Alan S. Silvestri, Guido TI CD8+Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells SO PLOS PATHOGENS LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; HIV-1 INFECTION; TYPE-1 INFECTION; SOOTY MANGABEYS; ANTIRETROVIRAL THERAPY; AIDS PATHOGENESIS; VACCINE DESIGN; CLEARANCE RATE; NK CELLS AB While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short-or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication. C1 [Klatt, Nichole R.; Ortiz, Alex M.; Engram, Jessica C.; Paiardini, Mirko; Silvestri, Guido] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Klatt, Nichole R.; Lawson, Benton; Else, James; Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Shudo, Emi; Ribeiro, Ruy M.; Perelson, Alan S.] Los Alamos Natl Lab, Los Alamos, NM USA. [Miller, Michael D.] Gilead Sci Inc, Foster City, CA 94404 USA. [Pandrea, Ivona; Apetrei, Cristian] Tulane Univ, Tulane Natl Primate Res Ctr, New Orleans, LA 70118 USA. [Pandrea, Ivona; Apetrei, Cristian] Tulane Univ, Tulane Hlth Sci Ctr, New Orleans, LA 70118 USA. [Estes, Jacob D.] Sci Applicat Int Corp Frederick Inc, Natl Canc Inst, AIDS & Canc Virus Program, Frederick, MD USA. [Schmitz, Joern E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Klatt, NR (reprint author), Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM gsilvest@mail.med.upenn.edu OI Ribeiro, Ruy/0000-0002-3988-8241 FU NIH [AI66998, AI28433, RR06555, P20-RR18754, AI065335, RR-00165]; U.S. Department of Energy [AC52-06NA25396] FX This work was supported by NIH grants AI66998 (to GS), AI28433, RR06555, and P20-RR18754 (to ASP), AI065335 (to JES), and RR-00165 (Yerkes National Primate Research Center). Portions of this work were done under the auspices of the U.S. Department of Energy under contract DE-AC52-06NA25396. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 84 Z9 85 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2010 VL 6 IS 1 AR e1000747 DI 10.1371/journal.ppat.1000747 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 551RQ UT WOS:000274227100036 PM 20126441 ER PT J AU Valmas, C Grosch, MN Schumann, M Olejnik, J Martinez, O Best, SM Krahling, V Basler, CF Muhlberger, E AF Valmas, Charalampos Grosch, Melanie N. Schuemann, Michael Olejnik, Judith Martinez, Osvaldo Best, Sonja M. Kraehling, Verena Basler, Christopher F. Muehlberger, Elke TI Marburg Virus Evades Interferon Responses by a Mechanism Distinct from Ebola Virus SO PLOS PATHOGENS LA English DT Article ID VESICULAR STOMATITIS-VIRUS; MATRIX PROTEIN VP40; NF-KAPPA-B; TYROSINE KINASE JAK1; I-INTERFERON; VP35 PROTEIN; V-PROTEIN; NUCLEAR ACCUMULATION; SIGNAL-TRANSDUCTION; ANTIVIRAL RESPONSE AB Previous studies have demonstrated that Marburg viruses (MARV) and Ebola viruses (EBOV) inhibit interferon (IFN)-alpha/beta signaling but utilize different mechanisms. EBOV inhibits IFN signaling via its VP24 protein which blocks the nuclear accumulation of tyrosine phosphorylated STAT1. In contrast, MARV infection inhibits IFN alpha/beta induced tyrosine phosphorylation of STAT1 and STAT2. MARV infection is now demonstrated to inhibit not only IFN alpha/beta but also IFN gamma-induced STAT phosphorylation and to inhibit the IFN alpha/beta and IFN gamma-induced tyrosine phosphorylation of upstream Janus (Jak) family kinases. Surprisingly, the MARV matrix protein VP40, not the MARV VP24 protein, has been identified to antagonize Jak and STAT tyrosine phosphorylation, to inhibit IFN alpha/beta or IFN gamma-induced gene expression and to inhibit the induction of an antiviral state by IFN alpha/beta. Global loss of STAT and Jak tyrosine phosphorylation in response to both IFN alpha/beta and IFN gamma is reminiscent of the phenotype seen in Jak1-null cells. Consistent with this model, MARV infection and MARV VP40 expression also inhibit the Jak1-dependent, IL-6-induced tyrosine phosphorylation of STAT1 and STAT3. Finally, expression of MARV VP40 is able to prevent the tyrosine phosphorylation of Jak1, STAT1, STAT2 or STAT3 which occurs following overexpression of the Jak1 kinase. In contrast, MARV VP40 does not detectably inhibit the tyrosine phosphorylation of STAT2 or Tyk2 when Tyk2 is over-expressed. Mutation of the VP40 late domain, essential for efficient VP40 budding, has no detectable impact on inhibition of IFN signaling. This study shows that MARV inhibits IFN signaling by a mechanism different from that employed by the related EBOV. It identifies a novel function for the MARV VP40 protein and suggests that MARV may globally inhibit Jak1-dependent cytokine signaling. C1 [Valmas, Charalampos; Martinez, Osvaldo; Basler, Christopher F.] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA. [Grosch, Melanie N.; Olejnik, Judith; Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Grosch, Melanie N.; Olejnik, Judith; Muehlberger, Elke] Natl Emerging Infect Dis Labs Inst, Boston, MA USA. [Grosch, Melanie N.; Schuemann, Michael; Olejnik, Judith; Kraehling, Verena; Muehlberger, Elke] Univ Marburg, Dept Virol, Marburg, Germany. [Best, Sonja M.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Valmas, C (reprint author), Mt Sinai Sch Med, Dept Microbiol, New York, NY USA. EM chris.basler@mssm.edu; muehlber@bu.edu RI Valmas, Charalampos/E-7269-2010; OI Martinez, Osvaldo/0000-0001-7335-4342; Muhlberger, Elke/0000-0003-3547-9376 FU German Research Foundation [SFB 535]; Boston University; National Institutes of Health (NIH) [AI059536, AI057158]; National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by funds from the German Research Foundation (SFB 535) and by start-up funds from Boston University to E. M., and by National Institutes of Health (NIH) grants AI059536 and AI057158 (Northeast Biodefense Center-Lipkin) to C. F. B. S. M. B. was supported by the intramural research program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 80 TC 77 Z9 79 U1 0 U2 18 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2010 VL 6 IS 1 AR e1000721 DI 10.1371/journal.ppat.1000721 PG 16 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 551RQ UT WOS:000274227100012 PM 20084112 ER PT S AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, Ferenc Basser, Peter J. Hecht, Anne-Marie Geissler, Erik BE Patrickios, CS TI Counterion and pH-Mediated Structural Changes in Charged Biopolymer Gels SO POLYMER NETWORKS: SYNTHESIS, PROPERTIES, THEORY AND APPLICATIONS SE Macromolecular Symposia LA English DT Proceedings Paper CT 19th Polymer-Networks-Group Meeting CY JUN 22-26, 2008 CL Larnaca, CYPRUS SP Univ Cyprus, Polymer Networks Group, European Assoc Chem & Mol Sci (EuCheMS), Cyprus Res Promot Fdn, Medochemie Ltd DE DNA gel; ion exchange; osmotic pressure; small-angle neutron scattering; volume transition ID THERMODYNAMIC OBSERVATIONS; NETWORKS; SWOLLEN; SCATTERING; PROMOTER AB DNA solutions and gels exhibit a wide range of phenomena, many of which have not yet been fully understood. In the presence of multivalent counterions, attraction between charged DNA strands occurs. Increasing the concentration of multivalent ions leads to a decrease of the osmotic pressure, and a sufficiently high ion concentration results in the precipitation of the polymer. Replacing the monovalent counterions by hydrogen ions (decreasing the pH) also produces a marked decrease of the osmotic pressure, and at low pH a phase transition takes place. In this paper we analyze osmotic swelling pressure measurements and small-angle neutron scattering (SANS) measurements made on chemically cross-linked DNA gels swollen in near physiological salt solutions. The effect of calcium ions is compared with that of decreasing the pH of the equilibrium salt solution. We demonstrate that both the concentration dependence of the osmotic pressure and the SANS response of DNA gels display significant differences in the two cases. C1 [Horkay, Ferenc; Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Phys Biol, NIH, 13 South Dr, Bethesda, MD 20892 USA. [Hecht, Anne-Marie; Geissler, Erik] Univ Grenoble 1, CNRS UMR, Spectrometrie Phys Lab, F-38402 Grenoble, France. RP Horkay, F (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Phys Biol, NIH, 13 South Dr, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov FU Intramural Research Program of the NICHD, NIH; National Institute of Standards and Technology; U.S. Department of Commerce; National Science Foundation [DMR-0454672] FX This research was supported by the Intramural Research Program of the NICHD, NIH. The authors acknowledge the support of the National Institute of Standards and Technology, U.S. Department of Commerce for providing access to the NG3 small angle neutron scattering instrument used in this experiment. This work utilized facilities supported in part by the National Science Foundation under Agreement No. DMR-0454672. NR 23 TC 1 Z9 1 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP PY 2010 VL 291-292 BP 354 EP + DI 10.1002/masy.201050542 PG 2 WC Polymer Science SC Polymer Science GA BTT85 UT WOS:000288039200042 PM 23125517 ER PT S AU Geissler, E Hecht, AM Horkay, F AF Geissler, E. Hecht, A. -M. Horkay, F. BE Patrickios, CS TI Scaling Behavior of Hyaluronic Acid in Solution with Mono- and Divalent Ions SO POLYMER NETWORKS: SYNTHESIS, PROPERTIES, THEORY AND APPLICATIONS SE Macromolecular Symposia LA English DT Proceedings Paper CT 19th Polymer-Networks-Group Meeting CY JUN 22-26, 2008 CL Larnaca, CYPRUS SP Univ Cyprus, Polymer Networks Group, European Assoc Chem & Mol Sci (EuCheMS), Cyprus Res Promot Fdn, Medochemie Ltd DE collective diffusion; dynamic light scattering; ion distribution; ionic strength; osmotic compression modulus; polyelectrolyte solutions ID SEMIDILUTE POLYELECTROLYTE SOLUTIONS; LIGHT-SCATTERING; MOLECULAR-WEIGHT; DEPENDENCE; HYDROGELS; SALT AB The effect of the simultaneous presence of mono- and divalent cations on the thermodynamics of polyelectrolyte solutions is not fully understood. In physiological conditions, combinations of these ions affect structure formation in biopolymer systems. It is known that divalent counterions form a tight sheath around the polymer backbone, while monovalent ions are distributed in a diffuse cloud. Dynamic light scattering measurements of the collective diffusion coefficient D and the osmotic compressibility of semi-dilute hyaluronan solutions containing different ratios of sodium and calcium ions are compared with simple polyelectrolyte models. Scaling relationships are derived in terms of polymer concentration and ionic strength J of the added salt. Differences in the effects of sodium and calcium ions are expressed only through J. C1 [Geissler, E.; Hecht, A. -M.] Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, BP 87, F-38402 St Martin Dheres, France. [Horkay, F.] NICHHD, NIH, Pro Phy Biolog, Bethesda, MD 20892 USA. RP Geissler, E (reprint author), Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, BP 87, F-38402 St Martin Dheres, France. EM erik.geissler@ujf-grenoble.fr RI d2am, beamline/I-6445-2015 FU Intramural Research Program of the NICHD, NIH, USA; National Institute of Standards and Technology; U.S. Department of Commerce; European Synchrotron Radiation Facility; National Science Foundation under Agreement [DMR-0454672] FX This research was supported by the Intramural Research Program of the NICHD, NIH, USA. The authors acknowledge the support of the National Institute of Standards and Technology, U.S. Department of Commerce for providing access to the NG3 small angle neutron scattering instrument and also to the European Synchrotron Radiation Facility for access to beam line BM2. The work utilized facilities supported in part by the National Science Foundation under Agreement No. DMR-0454672. NR 15 TC 3 Z9 3 U1 3 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP PY 2010 VL 291-292 BP 362 EP + DI 10.1002/masy.201050543 PG 3 WC Polymer Science SC Polymer Science GA BTT85 UT WOS:000288039200043 PM 21984864 ER PT J AU Rehm, J Kehoe, T Gmel, G Stinson, F Grant, B Gmel, G AF Rehm, Juergen Kehoe, Tara Gmel, Gerrit Stinson, Fred Grant, Bridget Gmel, Gerhard TI Statistical modeling of volume of alcohol exposure for epidemiological studies of population health: the US example SO POPULATION HEALTH METRICS LA English DT Article AB Background: Alcohol consumption is a major risk factor in the global burden of disease, with overall volume of exposure as the principal underlying dimension. Two main sources of data on volume of alcohol exposure are available: surveys and per capita consumption derived from routine statistics such as taxation. As both sources have significant problems, this paper presents an approach that triangulates information from both sources into disaggregated estimates in line with the overall level of per capita consumption. Methods: A modeling approach was applied to the US using data from a large and representative survey, the National Epidemiologic Survey on Alcohol and Related Conditions. Different distributions (log-normal, gamma, Weibull) were used to model consumption among drinkers in subgroups defined by sex, age, and ethnicity. The gamma distribution was used to shift the fitted distributions in line with the overall volume as derived from per capita estimates. Implications for alcohol-attributable fractions were presented, using liver cirrhosis as an example. Results: The triangulation of survey data with aggregated per capita consumption data proved feasible and allowed for modeling of alcohol exposure disaggregated by sex, age, and ethnicity. These models can be used in combination with risk relations for burden of disease calculations. Sensitivity analyses showed that the gamma distribution chosen yielded very similar results in terms of fit and alcohol-attributable mortality as the other tested distributions. Conclusions: Modeling alcohol consumption via the gamma distribution was feasible. To further refine this approach, research should focus on the main assumptions underlying the approach to explore differences between volume estimates derived from surveys and per capita consumption figures. C1 [Rehm, Juergen; Kehoe, Tara; Gmel, Gerrit; Gmel, Gerhard] CAMH, Toronto, ON M5S 2S1, Canada. [Rehm, Juergen] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada. [Rehm, Juergen] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, D-01187 Dresden, Germany. [Kehoe, Tara] Univ Toronto, Dept Stat, Toronto, ON M5S 3G3, Canada. [Stinson, Fred; Grant, Bridget] NIAAA, NIH, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Rockville, MD 20852 USA. [Gmel, Gerhard] Swiss Inst Prevent Alcohol & Drug Problems, CH-1001 Lausanne, Switzerland. [Gmel, Gerhard] Univ Lausanne Hosp, Alcohol Treatment Ctr, CH-1011 Lausanne, Switzerland. [Gmel, Gerhard] Univ W England, Bristol BS16 1QY, Avon, England. RP Rehm, J (reprint author), CAMH, 33 Russell St, Toronto, ON M5S 2S1, Canada. EM jtrehm@aol.com NR 37 TC 69 Z9 69 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-7954 J9 POPUL HEALTH METR JI Popul. Health Metr. PY 2010 VL 8 AR 3 DI 10.1186/1478-7954-8-3 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V21QF UT WOS:000208221400003 PM 20202213 ER PT B AU Shek, DTL Ma, HK Merrick, J AF Shek, Daniel T. L. Ma, Hing Keung Merrick, Joav BE Shek, DTL Ma, HK Merrick, J TI PROMOTING POSITIVE DEVELOPMENT IN CHINESE ADOLESCENTS SO POSITIVE YOUTH DEVELOPMENT: EVALUATION AND FUTURE DIRECTIONS IN A CHINESE CONTEXT SE Health and Human Development LA English DT Article; Book Chapter ID HEALTH PSYCHOLOGY; PUBLIC-HEALTH; HONG-KONG; PREVENTION; YOUTH AB To promote holistic development among adolescents in Hong Kong, The Hong Kong Jockey Club Charities Trust approved HK$400 million to launch a project entitled "P.A.T.H.S. to Adulthood: A Jockey Club Youth Enhancement Scheme". The word "P.A.T.H.S." denotes Positive Adolescent Training through Holistic Social Programs. The Trust invited academics of five universities in Hong Kong to form a Research Team with The Hong Kong Polytechnic University as the lead institution to develop a multi-year universal positive youth development program to promote holistic adolescent development in Hong Kong. Besides developing the program, the Research Team also provides training for teachers and social workers who implement the program and carry out longitudinal evaluation of the project. This book is one of the evaluations of the project. C1 [Shek, Daniel T. L.] Hong Kong Polytech Univ, Dept Appl Social Sci, Hunghom, Hong Kong, Peoples R China. [Shek, Daniel T. L.] E China Normal Univ, Dept Sociol, Shanghai 200062, Peoples R China. [Shek, Daniel T. L.] Kiang Wu Nursing Coll Macau, Macao, Peoples R China. [Ma, Hing Keung] Hong Kong Baptist Univ, Dept Educ Studies, Fac Social Sci, Hong Kong, Hong Kong, Peoples R China. [Merrick, Joav] NICHHD, Bethesda, MD USA. [Merrick, Joav] Minist Social Affairs, Div Mental Retardat, Jerusalem, Israel. [Merrick, Joav] Univ Kentucky, Kentucky Childrens Hosp, Lexington, KY 40506 USA. RP Shek, DTL (reprint author), Hong Kong Polytech Univ, Dept Appl Social Sci, Hunghom, Hong Kong, Peoples R China. EM daniel.shek@polyu.edu.hk; daniel.shek@polyu.edu.hk NR 15 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-830-1 J9 HEALTH HUM DEV PY 2010 BP 7 EP 13 PG 7 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BSF99 UT WOS:000284350900003 ER PT B AU Shek, DTL Ma, HK Merrick, J AF Shek, Daniel T. L. Ma, Hing Keung Merrick, Joav BE Shek, DTL Ma, HK Merrick, J TI POSITIVE YOUTH DEVELOPMENT: EVALUATION AND FUTURE DIRECTIONS IN A CHINESE CONTEXT PREFACE SO POSITIVE YOUTH DEVELOPMENT: EVALUATION AND FUTURE DIRECTIONS IN A CHINESE CONTEXT SE Health and Human Development LA English DT Editorial Material; Book Chapter C1 [Shek, Daniel T. L.] Hong Kong Polytech Univ, Dept Appl Social Sci, Hunghom, Hong Kong, Peoples R China. [Shek, Daniel T. L.] E China Normal Univ, Shanghai, Peoples R China. [Shek, Daniel T. L.] Kiang Wu Nursing Coll Macau, Macao, Peoples R China. [Ma, Hing Keung] Hong Kong Baptist Univ, Dept Educ Studies, Kowloon Tong, Hong Kong, Peoples R China. [Ma, Hing Keung] Hong Kong Psychol Soc, Hong Kong, Hong Kong, Peoples R China. [Merrick, Joav] Univ Kentucky, Kentucky Childrens Hosp, Lexington, KY 40506 USA. [Merrick, Joav] Ben Gurion Univ Negev, Soroka Univ Med Ctr, Div Pediat, Zusman Child Dev Ctr, Beer Sheva, Israel. [Merrick, Joav] Minist Social Affairs, Div Mental Retardat, Hlth Serv, Jerusalem, Israel. [Merrick, Joav] NICHHD, Bethesda, MD USA. RP Shek, DTL (reprint author), Hong Kong Polytech Univ, Dept Appl Social Sci, Hunghom, Hong Kong, Peoples R China. EM daniel.shek@polyu.edu.hk; hkma@hkbu.edu.hk; jmerrick@zahav.net.il; daniel.shek@polyu.edu.hk; hkma@hkbu.edu.hk; jmerrick@zahav.net.il NR 0 TC 0 Z9 0 U1 0 U2 0 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-830-1 J9 HEALTH HUM DEV PY 2010 BP XI EP XVI PG 6 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BSF99 UT WOS:000284350900001 ER PT B AU Shek, DTL Ma, HK Merrick, J AF Shek, Daniel T. L. Ma, Hing Keung Merrick, Joav BE Shek, DTL Ma, HK Merrick, J TI POSITIVE YOUTH DEVELOPMENT AND PREVENTION PROGRAMS IN ADOLESCENCE IN THE CHINESE CULTURE: WHERE SHOULD WE GO? SO POSITIVE YOUTH DEVELOPMENT: EVALUATION AND FUTURE DIRECTIONS IN A CHINESE CONTEXT SE Health and Human Development LA English DT Article; Book Chapter AB Adolescent drug addiction problem, youth crime such as shoplifting and theft, adolescent mental health problem, unhealthy adolescent life styles such as smoking, early sex and moral confusion, adolescent poverty, youth unemployment and youth non-engagement, and family and parenting problems in families with adolescents are part of the modern adolescent development issues worldwide but also in Hong Kong. Positive youth development and adolescent prevention programs are basically products of the Western culture utilizing Western concepts in different disciplines (such as social work, psychology, sociology, adolescent medicine and nursing), but cultural considerations should be seriously taken into account when they are used in non-Western cultures. Unfortunately, issues of indigenization and cultural factors related to positive youth development and adolescent prevention programs have rarely been researched in the Chinese culture. In this chapter we consider the development of adolescent prevention and positive youth development programs in the Chinese culture. C1 [Shek, Daniel T. L.] Hong Kong Polytech Univ, Dept Appl Social Sci, Hunghom, Hong Kong, Peoples R China. [Shek, Daniel T. L.] E China Normal Univ, Dept Sociol, Shanghai 200062, Peoples R China. [Shek, Daniel T. L.] Kiang Wu Nursing Coll Macau, Macao, Peoples R China. [Ma, Hing Keung] Hong Kong Baptist Univ, Dept Educ Studies, Fac Social Sci, Hong Kong, Hong Kong, Peoples R China. [Merrick, Joav] NICHHD, Bethesda, MD USA. [Merrick, Joav] Minist Social Affairs, Div Mental Retardat, Off Med Director, Jerusalem, Israel. [Merrick, Joav] Univ Kentucky, Kentucky Childrens Hosp, Lexington, KY 40506 USA. RP Shek, DTL (reprint author), Hong Kong Polytech Univ, Dept Appl Social Sci, Hunghom, Hong Kong, Peoples R China. EM daniel.shek@polyu.edu.hk; hkma@hkbu.edu.hk; jmerrick@zahav.net.il; daniel.shek@polyu.edu.hk; hkma@hkbu.edu.hk; jmerrick@zahav.net.il NR 12 TC 1 Z9 1 U1 0 U2 1 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60876-830-1 J9 HEALTH HUM DEV PY 2010 BP 137 EP 143 PG 7 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BSF99 UT WOS:000284350900013 ER PT J AU Chamouton, J Hansmannel, F Bonzo, JA Clemencet, MC Chevillard, G Battle, M Martin, P Pineau, T Duncan, S Gonzalez, FJ Latruffe, N Mandard, S Nicolas-Frances, V AF Chamouton, J. Hansmannel, F. Bonzo, J. A. Clemencet, M. C. Chevillard, G. Battle, M. Martin, P. Pineau, T. Duncan, S. Gonzalez, F. J. Latruffe, N. Mandard, S. Nicolas-Frances, V. TI The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPAR alpha and HNF4 alpha in the Liver SO PPAR RESEARCH LA English DT Article ID PROLIFERATOR-ACTIVATED-RECEPTOR; THIOLASE-B GENE; HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; ADRENOLEUKODYSTROPHY-RELATED GENE; RESPONSE ELEMENTS; BETA-OXIDATION; TARGET GENE; FATTY-ACID; RAT-LIVER; LIPID-METABOLISM AB PPAR alpha and HNF4 alpha are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPAR alpha or HNF4 alpha, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B (Thb) is under the dependence of these two transcription factors. Transactivation and gel shift experiments identified a novel PPAR response element within intron 3 of the Thb gene, by which PPAR alpha but not HNF4 alpha transactivates. Intriguingly, we found that HNF4 alpha enhanced PPAR alpha/RXR alpha transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4 alpha was physically interacting with RXR alpha. RT-PCR performed with RNA from liver-specific HNF4 alpha-null mice confirmed the involvement of HNF4 alpha in the PPAR alpha-regulated induction of Thb by Wy14,643. Overall, we conclude that HNF4 alpha enhances the PPAR alpha-mediated activation of Thb gene expression in part through interaction with the obligate PPAR alpha partner, RXR alpha. C1 [Chamouton, J.; Hansmannel, F.; Clemencet, M. C.; Chevillard, G.; Latruffe, N.; Mandard, S.; Nicolas-Frances, V.] INSERM, U866, LBMN 6, Ctr Rech, F-21000 Dijon, France. [Chamouton, J.; Hansmannel, F.; Clemencet, M. C.; Chevillard, G.; Latruffe, N.; Mandard, S.; Nicolas-Frances, V.] Univ Bourgogne, Fac Sci Gabriel, LBMN, F-21000 Dijon, France. [Hansmannel, F.] Inst Pasteur, Lab Epidemiol & Sante Publ, INSERM, U744, F-59019 Lille, France. [Bonzo, J. A.; Gonzalez, F. J.] NCI, Lab Metab, Div Basic Sci, Bethesda, MD 20892 USA. [Chevillard, G.] McGill Univ, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Battle, M.; Duncan, S.] Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA. [Martin, P.; Pineau, T.] INRA, UR66, Lab Pharmacol & Toxicol, F-31931 Toulouse, France. RP Mandard, S (reprint author), INSERM, U866, LBMN 6, Ctr Rech, Blvd Gabriel, F-21000 Dijon, France. EM stephane.mandard@u-bourgogne.fr FU Ministry of Research, National Education and Technology; Regional Council of Burgundy; GDR-CNRS [2583]; French Ministry of Research, National Education and Technology; EU [LSHG-CT2004-512018]; National Institute of Diabetes and Digestive and Kidney Diseases of the US National Institutes of Health FX The authors are thankful to Dr. Arnaud Jacquel (Centre de Recherche INSERM U866, Dijon) for assisting with the AMAXA technology, Jacques Kaminski for his valuable help with the CoIP procedure and Dr. Tsutomo Matsubara for helpful advice. They would also like to thank Dr. T. Leff (Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA) for sharing DN HNF4 expression vector, Dr. B. Laine (Faculte de Medecine Henri Warembourg, Lille, France) for sharing pcDNA3.1hHNF4 alpha 2 and pcDNA3.1 D126Y HNF4 alpha 2. F. Hansmannel and G. Chevillard were recipients of a fellowship from the Ministry of Research, National Education and Technology. This work was supported by the Regional Council of Burgundy, the GDR-CNRS no2583 on peroxisome, the French Ministry of Research, National Education and Technology and the EU peroxisome project (Project No. LSHG-CT2004-512018). S. Duncan and M. Battle are supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the US National Institutes of Health. J. Chamouton and F. Hansmannel equally contributed to this work. S. Mandard and V. Nicolas-Frances are joined last authors. NR 58 TC 8 Z9 8 U1 1 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2010 AR 352957 DI 10.1155/2010/352957 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 760UH UT WOS:000290348900001 PM 21437216 ER PT J AU Cunningham, ML Collins, BJ Hejtmancik, MR Herbert, RA Travlos, GS Vallant, MK Stout, MD AF Cunningham, Michael L. Collins, Bradley J. Hejtmancik, Milton R. Herbert, Ronald A. Travlos, Gregory S. Vallant, Molly K. Stout, Matthew D. TI Effects of the PPAR alpha Agonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism SO PPAR RESEARCH LA English DT Article ID PROLIFERATOR-ACTIVATED-RECEPTOR; ZERO-DOSE CONTROL; <4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643; PEROXISOMAL ENZYME-ACTIVITIES; CORONARY-HEART-DISEASE; SPECIES-DIFFERENCES; HEPATOCELLULAR PROLIFERATION; CATALASE ACTIVITY; PHTHALATE-ESTERS; CLOFIBRIC ACID AB Gemfibrozil is a widely prescribed hypolipidemic agent in humans and a peroxisome proliferator and liver carcinogen in rats. Three-month feed studies of gemfibrozil were conducted by the National Toxicology Program (NTP) in male Harlan Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters, primarily to examine mechanisms of hepatocarcinogenicity. There was morphologic evidence of peroxisome proliferation in rats and mice. Increased hepatocyte proliferation was observed in rats, primarily at the earliest time point. Increases in peroxisomal enzyme activities were greatest in rats, intermediate in mice, and least in hamsters. These studies demonstrate that rats are most responsive while hamsters are least responsive. These events are causally related to hepatotoxicity and hepatocarcinogenicity of gemfibrozil in rodents via peroxisome proliferator activated receptor-alpha (PPAR alpha) activation; however, there is widespread evidence that activation of PPARa in humans results in expression of genes involved in lipid metabolism, but not in hepatocellular proliferation. C1 [Cunningham, Michael L.; Collins, Bradley J.; Hejtmancik, Milton R.; Herbert, Ronald A.; Travlos, Gregory S.; Vallant, Molly K.; Stout, Matthew D.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Cunningham, ML (reprint author), NIEHS, Natl Toxicol Program, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cunning1@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [1 Z01 ESO45004-11] FX This research was supported (in part) by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences under Research Project number 1 Z01 ESO45004-11 BB. The authors wish to thank Dr. Dan Marsman for contribution to the design of the studies and Drs. Alex Merrick and Chris Corton for critical review of the manuscript. NR 79 TC 3 Z9 3 U1 1 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 EI 1687-4765 J9 PPAR RES JI PPAR Res. PY 2010 AR 681963 DI 10.1155/2010/681963 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 670MJ UT WOS:000283425900001 ER PT J AU Lau, C Abbott, BD Corton, JC Cunningham, ML AF Lau, Christopher Abbott, Barbara D. Corton, J. Christopher Cunningham, Michael L. TI PPARs and Xenobiotic-Induced Adverse Effects: Relevance to Human Health SO PPAR RESEARCH LA English DT Editorial Material ID ACTIVATED RECEPTOR-ALPHA; MOUSE; INDUCTION C1 [Lau, Christopher; Abbott, Barbara D.] US EPA, Tox Assessment Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Corton, J. Christopher] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Cunningham, Michael L.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Lau, C (reprint author), US EPA, Tox Assessment Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. EM lau.christopher@epamail.epa.gov NR 12 TC 8 Z9 8 U1 0 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 EI 1687-4765 J9 PPAR RES JI PPAR Res. PY 2010 AR 954639 DI 10.1155/2010/954639 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 802XX UT WOS:000293545400001 ER PT J AU Pollock, CB Rodriguez, O Martin, PL Albanese, C Li, X Kopelovich, L Glazer, RI AF Pollock, Claire B. Rodriguez, Olga Martin, Philip L. Albanese, Chris Li, Xin Kopelovich, Levy Glazer, Robert I. TI Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptor delta Activation SO PPAR RESEARCH LA English DT Article ID BETA/DELTA PPAR-BETA/DELTA; NF-KAPPA-B; COLON CARCINOGENESIS; TRANSCRIPTIONAL REPRESSION; GASTROINTESTINAL-TRACT; CELL-PROLIFERATION; GENETIC DISRUPTION; METABOLIC SYNDROME; SIGNALING PATHWAY; LIGAND ACTIVATION AB Peroxisome proliferator-activated receptord (PPAR delta) regulates a multiplicity of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes likely create risk factors associated with the ability of PPAR delta agonists to promote tumorigenesis in some organs. In the present study, we describe a new gastric tumor mouse model that is dependent on the potent and highly selective PPARd agonist GW501516 following carcinogen administration. The progression of gastric tumorigenesis was rapid as determined by magnetic resonance imaging and resulted in highly metastatic squamous cell carcinomas of the forestomach within two months. Tumorigenesis was associated with gene expression signatures indicative of cell adhesion, invasion, inflammation, and metabolism. Increased PPAR delta expression in tumors correlated with increased PDK1, Akt, beta-catenin, and S100A9 expression. The rapid development of metastatic gastric tumors in this model will be useful for evaluating preventive and therapeutic interventions in this disease. C1 [Pollock, Claire B.; Rodriguez, Olga; Albanese, Chris; Glazer, Robert I.] Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. [Martin, Philip L.] NCI Frederick, Ctr Adv Preclin Res, SAIC, Ft Detrick, MD 21702 USA. [Li, Xin] Lombardi Comprehens Canc Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA. [Kopelovich, Levy] NCI, Chemoprevent Agent Dev & Res Grp, Canc Prevent Div, Bethesda, MD 20814 USA. RP Glazer, RI (reprint author), Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. EM glazerr@georgetown.edu FU National Institutes of Health, Bethesda, MD [R01 CA111482, N01 CN43309]; National Center for Research Facilities [C06 RR14567]; National Cancer Institute [1P30-CA-51008] FX This work was supported by Grant no. R01 CA111482 and Contract no. N01 CN43309 from the National Institutes of Health, Bethesda, MD. This investigation was conducted using the Animal Research, Histopathology and Tissue, Genomics and Epigenomics, and Preclinical Imaging Shared Resources supported by Research Facilities Improvement Grant no. C06 RR14567 from the National Center for Research Facilities, and by Cancer Center Support Grant no. 1P30-CA-51008 from the National Cancer Institute. The authors thank Yi Chien Lee for his help with the MRI. NR 76 TC 16 Z9 16 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2010 AR 571783 DI 10.1155/2010/571783 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 707CL UT WOS:000286264000001 ER PT J AU Meyerle, CB Chew, EY AF Meyerle, Catherine B. Chew, Emily Y. BE McCance, DR Maresh, M Sacks, DA TI Retinopathy in diabetes in pregnancy SO PRACTICAL MANUAL OF DIABETES IN PREGNANCY LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-PRESSURE CONTROL; MICROVASCULAR COMPLICATIONS; UNITED-STATES; HARD EXUDATE; RISK-FACTOR; PROGRESSION; MELLITUS; ASSOCIATION; TRIAL C1 [Meyerle, Catherine B.] NIH, Clin Trials Branch, NEI, Bethesda, MD 20892 USA. [Chew, Emily Y.] NIH, Div Epidemiol & Clin Applicat, NEI, Bethesda, MD 20892 USA. RP Meyerle, CB (reprint author), NIH, Clin Trials Branch, NEI, Bldg 10, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-405-17904-1 PY 2010 BP 165 EP 175 DI 10.1002/9781444315196.ch17 D2 10.1002/9781444315196 PG 11 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA BUC23 UT WOS:000288792200019 ER EF