FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Maqbool, A Dougherty, K Rovner, AJ Michel, SH Stallings, VA AF Maqbool, Asim Dougherty, Kelly Rovner, Alisha J. Michel, Suzanne H. Stallings, Virginia A. BE Allen, JL Panitch, HB Rubenstein, RC TI Nutrition SO CYSTIC FIBROSIS SE Lung Biology in Health and Disease LA English DT Article; Book Chapter ID CYSTIC-FIBROSIS PATIENTS; VITAMIN-D DEFICIENCY; POLYUNSATURATED FATTY-ACIDS; PANCREATIC-ENZYME USE; PREADOLESCENT CHILDREN; PULMONARY-FUNCTION; DIETARY-INTAKE; S-ADENOSYLHOMOCYSTEINE; PLASMA HOMOCYSTEINE; ZINC CONCENTRATIONS C1 [Maqbool, Asim; Dougherty, Kelly; Michel, Suzanne H.; Stallings, Virginia A.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Rovner, Alisha J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Maqbool, A (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. NR 109 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 978-1-4398-0182-6; 978-1-4398-0181-9 J9 LUNG BIOL HEALTH DIS PY 2010 VL 242 BP 308 EP 327 PG 20 WC Respiratory System SC Respiratory System GA BC5GA UT WOS:000353242800020 ER PT J AU Dutra, A Pak, E Wincovitch, S John, K Poirier, MC Olivero, OA AF Dutra, A. Pak, E. Wincovitch, S. John, K. Poirier, M. C. Olivero, O. A. TI Nuclear Bud Formation: A Novel Manifestation of Zidovudine Genotoxicity SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article DE Aneuploidy; AZT; FISH; Mouse painting probes; Nuclear buds; Zidovudine ID REVERSE-TRANSCRIPTASE INHIBITORS; HUMAN-LYMPHOCYTES; CELLS; DNA; AMPLIFICATION; HYBRIDIZATION; MICRONUCLEI; CHROMOSOMES; ANEUPLOIDY AB Normal diploid somatic mammalian cell division generates 2 daughter cells as a result of a strict and well-controlled mitotic process. However, some defects during the progression of that process could generate an unbalanced distribution of chromosomes, aneuploidy and eventually, a malignant phenotype. Previous observations using a transgenic mouse model with diminished DNA repair capacity revealed the presence of nuclear buds (NBs) induced in vitro by the nucleoside analog zidovudine (Retrovir (R), 3'-azido-3'-deoxythymidine, AZT). Here we used bone marrow mesenchymal cells, taken from mice with the Xpa(-/-) Trp53(+/-) genotype, that were cultured and exposed to 0 and 100 mu M AZT for 24 hours. Fixed and denatured cells were processed by fluorescence in situ hybridization (FISH) with whole chromosome painting probes used to identify chromosomes in cells growing on glass chamber slides (2 probes/slide). A variety of sizes and shapes of NBs were observed. Some NBs had a large connection with the main nucleus (>1/4 of the NB diameter), others had a smaller connection (<1/4 of the NB diameter), some were circular and positioned close to the nucleus, while some resided in the cytoplasm separated from the nucleus or connected by a thin chromatin strand. We had hypothesized that NBs would progress in the process of budding until separation occurred, but this was not proven by time-lapse photography studies performed for 20 hours. From 1,126 cells scored in the unexposed cultures, 10.39 % of cells carried NBs, while from 1,108 cells scored in the AZT-exposed cultures 29.16% of cells carried NBs (p = 0.001). In AZT-exposed cells there were a total of 322 NBs scored; 46.6% or 150 NBs contained positive signals for one or both probes used, while 53% or 172 NBs had no probe signal. In addition, FISH analysis showed no preferential localization of any chromosome within the NBs. Among the NBs that carried no probe signal, the presence of positive signals with inversion of DAPI imaging demonstrated centromeric content. It has been hypothesized that NBs occur as a result of expulsion of amplified DNA from the main nucleus; however, this data demonstrates that NBs may contain any chromosome, suggesting that NBs do not consist of just amplified DNA. Copyright (C) 2010 S. Karger AG, Basel C1 [Olivero, O. A.] NCI, NIH, Lab Canc Biol & Genet, Ctr Canc Res,Carcinogen DNA Interact Sect, Bethesda, MD 20892 USA. [Dutra, A.; Pak, E.; Wincovitch, S.] NHGRI, Bethesda, MD 20892 USA. RP Olivero, OA (reprint author), NCI, NIH, Lab Canc Biol & Genet, Ctr Canc Res,Carcinogen DNA Interact Sect, 37 Convent Dr,MSC 4255,Bldg 37 Rm 4032, Bethesda, MD 20892 USA. EM olivero@exchange.nih.gov NR 16 TC 18 Z9 20 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2010 VL 128 IS 1-3 BP 105 EP 110 DI 10.1159/000298794 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 605YA UT WOS:000278383500013 PM 20407220 ER PT J AU Spidlen, J Moore, W Parks, D Goldberg, M Bray, C Bierre, P Gorombey, P Hyun, B Hubbard, M Lange, S Lefebvre, R Leif, R Novo, D Ostruszka, L Treister, A Wood, J Murphy, RE Roederer, M Sudar, D Zigon, R Brinkman, RR AF Spidlen, Josef Moore, Wayne Parks, David Goldberg, Michael Bray, Chris Bierre, Pierre Gorombey, Peter Hyun, Bill Hubbard, Mark Lange, Simon Lefebvre, Ray Leif, Robert Novo, David Ostruszka, Leo Treister, Adam Wood, James Murphy, Robert E. Roederer, Mario Sudar, Damir Zigon, Robert Brinkman, Ryan R. TI Data File Standard for Flow Cytometry, Version FCS 3.1 SO CYTOMETRY PART A LA English DT Article DE flow cytometry; FCS; data standard; file format; bioinformatics AB The flow cytometry data file standard provides the specifications needed to completely describe flow cytometry data sets within the confines of the file containing the experimental data. In 1984, the first Flow Cytometry Standard format for data files was adopted as FCS 1.0. This standard was modified in 1990 as FCS 2.0 and again ill 1997 as FCS 3.0. We report here on the next generation flow cytometry standard data file format. FCS 3.1 is a minor revision based oil suggested improvements from the community The unchanged goal of the standard is to provide a uniform file format that allows Files created by one type of acquisition hardware and software to be analyzed by any other type. The FCS 3.1 standard retains the basic FCS file Structure and most features of previous versions of the standard. Changes included in FCS 3.1 address potential ambiguities in the previous versions and provide a more robust standard. The major changes include simplified support for international characters and improved support for storing compensation. The major additions are support for preferred display scale, a standardized way of capturing the sample volume, information about originality of the data file, and Support for plate and well identification in high throughput, plate based experiments. Please see the normative version of the FCS 3.1 specification ill Supporting Information for this manuscript (or at http://www.isac-net.org/ in the Current standards section) for a complete list of changes. (C) 2009 International Society for Advancement of Cytometry C1 [Spidlen, Josef; Brinkman, Ryan R.] BC Canc Agcy, Terry Fox Lab, Vancouver, BC, Canada. [Moore, Wayne] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Parks, David] Stanford Univ, Stanford Shared FACS Facil, Stanford, CA 94305 USA. [Goldberg, Michael] Becton Dickinson & Co, San Jose, CA USA. [Bray, Chris] Ver Software House, Topsham, ME USA. [Bierre, Pierre] Cytek Dev, Fremont, CA USA. [Gorombey, Peter] Soft Flow Informat, Debrecen, Hungary. [Hyun, Bill] Univ Calif San Francisco, Lab Cell Anal, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Hubbard, Mark] iCyt, Champaign, IL USA. [Lange, Simon] Partec GmBH, Gorlitz, Germany. [Lefebvre, Ray] Guava Technol, Hayward, CA USA. [Leif, Robert] Newport Instruments, San Diego, CA USA. [Novo, David] De Novo Software, Los Angeles, CA USA. [Ostruszka, Leo] Accuri Cytometers, Ann Arbor, MI USA. [Treister, Adam] Treestar Ltd, Ashland, OR USA. [Wood, James] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC USA. [Murphy, Robert E.] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Roederer, Mario] NIH, Bethesda, MD 20892 USA. [Sudar, Damir] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. [Zigon, Robert] Beckman Coulter, Indianapolis, IN USA. RP Brinkman, RR (reprint author), British Columbia Canc Res Ctr, Terry Fox Lab, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM rbrinkman@bccrc.ca RI Brinkman, Ryan/B-1108-2008; OI Brinkman, Ryan/0000-0002-9765-2990; Sudar, Damir/0000-0002-2510-7272 FU National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering [1R01EB005034]; Michael Smith Foundation for Health Research; U.S. Department of Energy [DE-AC02-05CH11231] FX Grant sponsor: National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering; Grant number: 1R01EB005034. This work was also partially supported by Michael Smith Foundation for Health Research and by the Director, Office of Science, Office of Biological and Environmental Research of the U.S. Department of Energy under contract No. DE-AC02-05CH11231. NR 7 TC 15 Z9 15 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD JAN PY 2010 VL 77A IS 1 BP 97 EP 100 DI 10.1002/cyto.a.20825 PG 4 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 541BA UT WOS:000273384700012 PM 19937951 ER PT J AU Caporaso, NE Marti, GE Vogt, RF Shim, YK Middleton, D Landgren, O AF Caporaso, Neil E. Marti, Gerald E. Vogt, Robert F., Jr. Shim, Youn K. Middleton, Dan Landgren, Ola CA Int MBL Study Grp TI Evolution of a Precursor SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOCYTOSIS; SUSCEPTIBILITY LOCI; NATURAL-HISTORY; CLASSIFICATION; FAMILIES; CLONES; COUNT C1 [Caporaso, Neil E.] NCI, Pharmacogenet Sect, Genet Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA. [Marti, Gerald E.] NIH, Flow & Image Cytometry Sect, CBER, US FDA, Bethesda, MD 20892 USA. [Vogt, Robert F., Jr.] Ctr Dis Control & Prevent, Newborn Screening Branch, Div Sci Lab, Atlanta, GA USA. [Shim, Youn K.; Middleton, Dan] ATSDR, Div Hlth Studies, Chamblee, GA 30341 USA. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Caporaso, NE (reprint author), NCI, Pharmacogenet Sect, Genet Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, EPS 7116,6120 Execut Blvd, Bethesda, MD 20892 USA. EM caporaso@nih.gov NR 22 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2010 VL 78B IS 1 BP 1 EP 2 DI 10.1002/cyto.b.20508 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 538EW UT WOS:000273168100001 PM 20014321 ER PT J AU Caporaso, NE Marti, GE Landgren, O Azzato, E Weinberg, JB Goldin, L Shanafelt, T AF Caporaso, Neil E. Marti, Gerald E. Landgren, Ola Azzato, Elizabeth Weinberg, J. Brice Goldin, Lynn Shanafelt, Tait TI Monoclonal B Cell Lymphocytosis: Clinical and Population Perspectives SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review DE chronic lymphocytic leukemia; monoclonal B cell lymphocytosis; population; lymphocytosis ID NATURAL-HISTORY; DIAGNOSTIC-CRITERIA; SUSCEPTIBILITY LOCI; FLOW-CYTOMETRY; LEUKEMIA; TRANSPLANTATION; CLASSIFICATION; FAMILIES; RISK; CLL AB Monoclonal B Cell Lymphocytosis (MBL) refers to clones of CLL-like cells that exhibit CLL characteristics that fall short of the numbers required for CLL diagnosis. Data from large CLL kindreds document increased prevalence of MBL suggesting a genetic contribution to its etiology. The molecular features that favor progression of MBL to CLL are poorly understood but an elevated B-cell count is a risk factor for progression. An important consideration when evaluating volunteers from CLL families who are willing to donate bone marrow is that MBL be ruled out since the MBL donor clone could result in a second CLL in the recipient. Further studies of MBL are needed to identify the molecular features and how they evolve during progression. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, EPS 7116, Bethesda, MD 20892 USA. [Marti, Gerald E.] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Res & Evaluat, Bethesda, MD 20892 USA. [Landgren, Ola] Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Weinberg, J. Brice] Duke Univ, Durham, NC 27705 USA. [Weinberg, J. Brice] VA Med Ctr, Durham, NC 27705 USA. [Shanafelt, Tait] Mayo Clin, Dept Med, Rochester, MN 55905 USA. RP Caporaso, NE (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, EPS 7116, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM caporaso@nih.gov NR 44 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2010 VL 78B SU 1 BP S115 EP S119 DI 10.1002/cyto.b.20555 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700016 PM 20839332 ER PT J AU McMaster, ML Landgren, O AF McMaster, Mary L. Landgren, Ola TI Prevalence, Clinical Aspects, and Natural History of IgM MGUS SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review DE MGUS; monoclonal gammopathy of undetermined significance; Waldenstrom macroglobulinemia; IgM; precursor disease; chronic lymphocytic leukemia ID UNDETERMINED SIGNIFICANCE MGUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; SMOLDERING MULTIPLE-MYELOMA; B-CELL LYMPHOCYTOSIS; TERM-FOLLOW-UP; MONOCLONAL GAMMOPATHY; MALIGNANT-TRANSFORMATION; UNITED-STATES; WALDENSTROMS MACROGLOBULINEMIA; ADULT-POPULATION AB Background: Waldenstrtom macroglobulinemia (WM) and chronic lymphocytic leukemia (CLL) are related B-cell cancers that share several clinical and biological features. Both WM and CLL have associated precursor conditions: monoclonal gammopathy of undetermined significance (MGUS) of immunoglobulin M (IgM) type and monoclonal B-cell lymphocytosis (MBL), respectively. Recently, a case of MBL with an IgM MGUS was reported, suggesting a close biological relationship between these entities. While much is known about MGUS overall, investigations of IgM MGUS specifically have been fragmentary. Methods: In this article, we review data on the prevalence, clinical aspects and natural history of IgM MGUS, and focus on identifying gaps in our understanding of the complex relationships among B-cell malignancies and their precursors. Results: There appears to be marked heterogeneity in the prevalence of IgM MGUS across populations. However, studies have varied in definition, design, laboratory methods, and endpoints. IgM MGUS differs from non-IgM MGUS in certain respects, including prevalence across racial groups, rate of progression, and pattern of malignant outcomes. There are limited data regarding the coincident occurrence of IgM MGUS and MBL. Conclusions: Future studies incorporating both protein electrophoresis and flow cytometry are needed to define the underlying spectrum and causes of precursor development, risk factors for progression, and markers that distinguish low- and high-risk precursor patients. Published 2010 Wiley-Liss, Inc. C1 [McMaster, Mary L.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP McMaster, ML (reprint author), 6120 Execut Blvd,Room 7010, Bethesda, MD 20892 USA. EM Mary.McMaster@nih.hhs.gov FU NIH, NCI FX Grant sponsor: Intramural Research Program of the NIH, NCI. NR 58 TC 9 Z9 9 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2010 VL 78B SU 1 BP S91 EP S97 DI 10.1002/cyto.b.20550 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700013 PM 20839342 ER PT J AU Nieto, WG Almeida, J Teodosio, C Abbasi, F Allgood, SD Connors, F Rachel, JM Ghia, P Lanasa, MC Rawstron, AC Orfao, A Caporaso, NE Hanson, CA Shim, YK Vogt, RF Marti, GE AF Nieto, Wendy G. Almeida, Julia Teodosio, Cristina Abbasi, Fatima Allgood, Sallie D. Connors, Fiona Rachel, Jane M. Ghia, Paolo Lanasa, Mark C. Rawstron, Andy C. Orfao, Alberto Caporaso, Neil E. Hanson, Curt A. Shim, Youn K. Vogt, Robert F. Marti, Gerald E. TI Commentary: Comparison of Current Flow Cytometry Methods for Monoclonal B Cell Lymphocytosis Detection SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Editorial Material DE chronic lymphocytic leukemia; immunophenotyping; lymphocyte gating ID CHRONIC LYMPHOPROLIFERATIVE DISORDERS; MINIMAL RESIDUAL DISEASE; LEUKEMIA; CLONES; COUNT AB Monoclonal B cell lymphocytosis (MBL) is now recognized as the B-lymphocyte analogue of a monoclonal gammopathy of unknown significance. MBL can be the precursor of chronic lymphocytic leukemia or associated with non-Hodgkin's lymphoma. It may be associated with an autoimmune abnormality or be related to aging (immunosenescence). The combination of available new fluorochrome-conjugated monoclonal antibody reagents, multilaser instrumentation, and improved software tools have led to a new level of multicolor analysis of MBL. Presently, several centers, including the University of Salamanca (Spain), Duke University (Durham, NC), Mayo Clinic (Rochester, MN), and the National Cancer Institute (Bethesda, MD) in conjunction with the Genetics and Epidemiology of Familial chronic lymphocytic leukemia Consortium, the Food and Drug Administration (Bethesda, MD), and the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (Atlanta, GA) in collaboration with Saint Luke's Hospital (Kansas City, MO), the Universita Vita-Salute San Raffaele in Milan (Italy), and Leeds Teaching Hospital (UK) are all actively conducting studies on MBL. This commentary is an updated summary of the current methods used in these centers. It is important to note the diversity of use in reagents, instruments, and methods of analysis. Despite this diversity, there is a consensus in what constitutes the diagnosis of MBL and its subtypes. There is also an emerging consensus on what the next investigative steps should be. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Abbasi, Fatima; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Nieto, Wendy G.; Almeida, Julia; Teodosio, Cristina; Orfao, Alberto] Univ Salamanca, Serv Gen Citometria, CSIC, Ctr Invest Canc,IBMCC,USAL, E-37008 Salamanca, Spain. [Nieto, Wendy G.; Almeida, Julia; Teodosio, Cristina; Orfao, Alberto] Univ Salamanca, Dept Med, E-37008 Salamanca, Spain. [Allgood, Sallie D.; Lanasa, Mark C.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Connors, Fiona; Rawstron, Andy C.] Leeds Teaching Hosp, St Jamess Inst Oncol, Hematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England. [Rachel, Jane M.] St Lukes Hosp, Mol Diagnost & Flow Cytometry Lab, Kansas City, MO USA. [Ghia, Paolo] Univ Vita Salute San Raffaele, Dept Oncol, Div Mol Oncol, Lab Cell Neoplasia B, Milan, Italy. [Ghia, Paolo] Univ Vita Salute San Raffaele, Dept Oncol, Lymphoma Unit, Milan, Italy. [Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hanson, Curt A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Shim, Youn K.] Agcy Tox Subst & Dis Registry, Div Hlth Studies, Atlanta, GA USA. [Vogt, Robert F.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Ghia, Paolo] Ist Sci San Raffaele, Milan, Italy. RP Marti, GE (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM gemarti@mac.com RI Ghia, Paolo/K-7138-2016; OI Ghia, Paolo/0000-0003-3750-7342; Allgood, Sallie/0000-0002-0329-4572; Rawstron, Andy/0000-0003-0798-9790 NR 15 TC 5 Z9 5 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2010 VL 78B SU 1 BP S4 EP S9 DI 10.1002/cyto.b.20556 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700003 PM 20839336 ER PT J AU Rawstron, AC Shanafelt, T Lanasa, MC Landgren, O Hanson, C Orfao, A Hillmen, P Ghia, P AF Rawstron, Andy C. Shanafelt, Tait Lanasa, Mark C. Landgren, Ola Hanson, Curtis Orfao, Alberto Hillmen, Peter Ghia, Paolo TI Different Biology and Clinical Outcome According to the Absolute Numbers of Clonal B-Cells in Monoclonal B-Cell Lymphocytosis (MBL) SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE monoclonal B-cell lymphocytosis; chronic lymphocytic leukaemia; B-cells ID NATURAL-HISTORY; LEUKEMIA; BLOOD; PROGRESSION; GUIDELINES; PROGNOSIS; DIAGNOSIS; SURVIVAL; COUNT AB The biological and clinical relationship between Chronic Lymphocytic Leukaemia (CLL) and Monoclonal B-cell Lymphocytosis (MBL) has now been reported in some detail. This review investigates associations between biology and disease activity as they relate to the absolute numbers of abnormal cells. The clonal B-cells in CLL-type MBL are indistinguishable from CLL with respect to surface phenotype and the presence of chromosomal abnormalities. However, the majority of CLL-type MBL cases in the general population have very low numbers of clonal B-cells, typically in the range 0.1-10 per mu L, and such cases use different IGHV genes than higher-count CLL-type MBL cases and often show intraclonal heterogeneity. Cases with higher counts are biologically similar to CLL although there is a relationship between the CLL cell count at presentation and the likelihood of further clonal expansion. Individuals presenting with CLL cell counts above 2,000 per mu L are more likely to have gradually increasing B-cell counts over time and although the risk of requiring treatment for progressive CLL remains low there may be impaired normal B-cell activity. (C) 2010 International Clinical Cytometry Society C1 [Rawstron, Andy C.; Hillmen, Peter] St Jamess Inst Oncol, HMDS, Leeds LS9 7TF, W Yorkshire, England. [Rawstron, Andy C.; Hillmen, Peter] St Jamess Inst Oncol, Dept Hematol, Leeds LS9 7TF, W Yorkshire, England. [Shanafelt, Tait] Mayo Clin, Div Hematol, Dept Med, Rochester, MN USA. [Lanasa, Mark C.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hanson, Curtis] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Orfao, Alberto] Univ Hosp, Dept Med, Cytometry Serv, Canc Res Ctr,IBMCC,CSIC,USAL, Salamanca, Spain. [Orfao, Alberto] Univ Salamanca, E-37008 Salamanca, Spain. [Ghia, Paolo] Univ Vita Salute San Raffaele, Lab Cell Neoplasia B, Div Mol Oncol, Dept Oncol, Milan, Italy. [Ghia, Paolo] Ist Sci San Raffaele, I-20132 Milan, Italy. [Ghia, Paolo] Univ Vita Salute San Raffaele, Dept Oncol, Lymphoma Unit, Milan, Italy. RP Rawstron, AC (reprint author), St Jamess Inst Oncol, HMDS, Level 3 Bexley Wing,Beckett St, Leeds LS9 7TF, W Yorkshire, England. EM andy.rawstron@hmds.org.uk RI IBSAL, Secretaria/H-3719-2011; Ghia, Paolo/K-7138-2016; OI Ghia, Paolo/0000-0003-3750-7342; Rawstron, Andy/0000-0003-0798-9790 FU Leukaemia and Lymphoma Research; NCI; Bernstein Family Fund for Leukemia Research; AIRC-Milano; Fondazione Cariplo; Prin-Muir and Fondazione Anna Villa e Felice Rusconi-Varese; [5K23CA113408] FX Grant sponsors: Leukaemia and Lymphoma Research (www. beatbloodcancers.org) (to AR and PH); NCI; Grant number: 5K23CA113408 (to TS); Grant sponsors: Bernstein Family Fund for Leukemia Research (to ML); AIRC-Milano; Fondazione Cariplo; Prin-Muir and Fondazione Anna Villa e Felice Rusconi-Varese (to PG). NR 28 TC 37 Z9 38 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2010 VL 78B SU 1 BP S19 EP S23 DI 10.1002/cyto.b.20533 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700005 PM 20839333 ER PT J AU Salerno, E Yuan, Y Scaglione, BJ Marti, G Jankovic, A Mazzella, F Laurindo, MF Despres, D Baskar, S Rader, C Raveche, E AF Salerno, Erica Yuan, Yao Scaglione, Brian J. Marti, Gerald Jankovic, Alexander Mazzella, Fermina Laurindo, Maria Fernanda Despres, Daryl Baskar, Sivasubramanian Rader, Christoph Raveche, Elizabeth TI The New Zealand Black Mouse as a Model for the Development and Progression of Chronic Lymphocytic Leukemia SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE chronic lymphocytic leukemia; monoclonal B cell lymphocytosis; miR-16; murine model of CLL; New Zealand Black; side population ID B-CELL LYMPHOCYTOSIS; SIDE POPULATION; STEM-CELLS; CLL; GENES; CANCER; 13Q14; RNA; IDENTIFICATION; MICRORNA-16 AB Background: Similar to a subset of human patients who progress from monoclonal B lymphocytosis (MBL) to chronic lymphocytic leukemia (CLL), New Zealand Black (NZB) mice have an age-associated progression to CLL. The murine disease is linked to a genetic abnormality in microRNA mir-15a/16-1 locus, resulting in decreased mature miR-15a/16. Methods: Spleens of aging NZB were analyzed for the presence of B-1 cells via flow cytometry and for the presence of a side population (SP) via the ability of cells to exclude Hoechst 33342 dye. The SP was assayed for the presence of hyperdiploid B-1 clones and for the ability to differentiate into B-1 cells in vitro and transfer disease in vivo. In addition, enhanced apoptosis of chemoresistant NZB B-1 cells was examined by restoring miR-16 levels in nutlin-treated cells. Results: Aging NZB mice develop a B-1 expansion and clonal development that evolves from MBL into CLL. An expansion in SP is also seen. Although the SP did contain increased cells with stem cell markers, they lacked malignant B-1 cells and did not transfer disease in vivo. Similar to B-1 cells, splenic NZB SP also has decreased miR-15a/16 when compared with C57BI/6. Exogenous addition of miR15a/16 to NZB B-1 cells resulted in increased sensitivity to nutlin. Conclusion: NZB serve as an excellent model for studying the development and progression of age-associated CLL. NZB SP cells do not seem to contain cancer stem cells, but rather the B-1 stem cell. NZB B-1 chemoresistance may be related to reduced miR-15a/16 expression. (C) 2010 International Clinical Cytometry Society C1 [Salerno, Erica; Yuan, Yao; Scaglione, Brian J.; Mazzella, Fermina; Laurindo, Maria Fernanda; Raveche, Elizabeth] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Lab Med & Pathol, Newark, NJ 07103 USA. [Scaglione, Brian J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Marti, Gerald; Jankovic, Alexander] US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. [Despres, Daryl] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. [Baskar, Sivasubramanian; Rader, Christoph] NCI, NIH, Bethesda, MD 20892 USA. RP Raveche, E (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Lab Med & Pathol, MSB C512,185 S Orange Ave, Newark, NJ 07103 USA. EM raveches@umdnj.edu FU NIH NCI [R01CA129826]; NJCCR [09-1255-CCR-E0] FX The authors thank Brian D. Brown, Alessia Baccarini, Sukwinder Singh, and Howard S. Mostowski. This research was in part funded by NIH NCI R01CA129826 granted to E. Raveche and NJCCR pre-doctoral fellowship 09-1255-CCR-E0 awarded to E. Salerno. NR 50 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2010 VL 78B SU 1 BP S98 EP S109 DI 10.1002/cyto.b.20544 PG 12 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700014 PM 20839343 ER PT J AU Shim, YK Middleton, DC Caporaso, NE Rachel, JM Landgren, O Abbasi, F Raveche, ES Rawstron, AC Orfao, A Marti, GE Vogt, RF AF Shim, Youn K. Middleton, Dannie C. Caporaso, Neil E. Rachel, Jane M. Landgren, Ola Abbasi, Fatima Raveche, Elizabeth S. Rawstron, Andy C. Orfao, Alberto Marti, Gerald E. Vogt, Robert F. TI Prevalence of Monoclonal B-Cell Lymphocytosis: A Systematic Review SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Review DE monoclonal B-cell lymphocytosis; MBL; chronic lymphocytic leukemia; CLL; prevalence; epidemiology ID NATURAL-HISTORY; FLOW-CYTOMETRY; LEUKEMIA; BLOOD; DISEASE; BURDEN; CLONES AB Background: Individuals with monoclonal B-cell lymphocytosis (MBL) have been identified in clinic outpatients, in unaffected relatives of patients with chronic lymphocytic leukemia (CLL), and in general populations. MBL and its relationship with CLL have been actively investigated over the last decade. This report systematically reviews the prevalence of MBL in the context of the populations studied and the evolution of laboratory methods used to define MBL. Methods: To identify published studies that have assessed the prevalence of MBL, we systematically searched the MEDLINE (R) databases and consulted with members of the International MBL Study Group. We reviewed the 10 articles that were identified by this process. We abstracted information on study populations, laboratory tests, criteria for designating MBL, and the reported frequencies. Results: Three of the ten studies were published in 2009, three between 2007 and 2008, and four between 2002 and 2004. Reported prevalences varied widely, ranging from 0.12 to 18.2%. This variability was clearly associated with both the laboratory methods and the populations studied. MBL was more common among older individuals and kindred of persons with CLL. The most common MBL subtype was CLL-like MBL. Conclusions: Large population-based studies of MBL that employ standardized laboratory methods with a consensus case definition are needed to assess prevalence and establish risk factors. These studies should include prospective follow-up of MBL cases to determine the relationship between MBL and CLL. Data from original studies should be reported in sufficient detail to allow future synthesis of information from multiple studies, such as meta-analysis. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Shim, Youn K.; Middleton, Dannie C.] Agcy Tox Subst & Dis Registry, Div Hlth Studies, Atlanta, GA USA. [Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Rachel, Jane M.] St Lukes Hosp, Kansas City, MO USA. [Landgren, Ola] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Abbasi, Fatima; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Raveche, Elizabeth S.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Rawstron, Andy C.] Leeds Teaching Hosp, St Jamess Inst Oncol, Hematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England. [Orfao, Alberto] Univ Hosp, Dept Med, Cytometry Serv, Canc Res Ctr,IBMCC,CSIC,USAL, Salamanca, Spain. [Orfao, Alberto] Univ Salamanca, E-37008 Salamanca, Spain. [Vogt, Robert F.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA. RP Shim, YK (reprint author), Agcy Tox Subst & Dis Registry, Div Hlth Studies, Atlanta, GA USA. EM yshim@cdc.gov RI IBSAL, Secretaria/H-3719-2011; OI Rawstron, Andy/0000-0003-0798-9790 FU NCI NIH HHS [R01 CA129826, R01 CA129826-01A2] NR 30 TC 16 Z9 16 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PY 2010 VL 78B SU 1 BP S10 EP S18 DI 10.1002/cyto.b.20538 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 647BM UT WOS:000281590700004 PM 20839330 ER PT J AU He, DZZ Jia, SP Sato, T Zuo, J Andrade, LP Riordan, GP Kachar, B AF He, David Z. Z. Jia, Shuping Sato, Takashi Zuo, Jian Andrade, Leonardo P. Riordan, Gavin P. Kachar, Bechara TI Changes in Plasma Membrane Structure and Electromotile Properties in Prestin Deficient Outer Hair Cells SO CYTOSKELETON LA English DT Article DE outer hair cell motility; electromotility; prestin; hair cell; membrane cytoskeleton; cortical lattice ID MOTOR PROTEIN PRESTIN; FORCE GENERATION; GUINEA-PIG; COCHLEAR AMPLIFIER; SOMATIC STIFFNESS; MOTILITY; CHARGE; TRANSPORTER; CAPACITANCE; EXPRESSION AB Cochlear outer hair cells (OHCs) rapidly change their length and stiffness when their membrane potential is altered. Prestin, the motor protein for this electromotility, is present along the OHC lateral plasma membrane where there is a high density of intra-membrane protein particles (IMPs). However, it is not known to what extent prestin contributes to this unusual dense population of proteins and overall organization of the membrane to generate the unique electromechanical response of OHCs. We investigated the relationship of prestin with the IMPs, the underlying cortical cytoskeletal lattice, and electromotility in prestin-deficient mice. Using freeze-fracture, we observed a reduction in density and size of the IMPs that correlates with the reduction and absence of prestin in the heterozygous and homozygous mice, respectively. We also observed a reduction or absence of electromotility-related charge density, axial stiffness, and piezoelectric properties of the OHC. A comparison of the charge density with the number of IMPs suggests that prestin forms tetramers in the wild type but is likely to form lower number oligomers in the prestin-deficient OHCs from the heterozygous mice. Interestingly, the characteristic actin-based cortical cytoskeletal lattice that underlies the membrane is absent in the prestin-null OHCs, suggesting that prestin is also required for recruiting or maintaining the cortical cytoskeletal lattice. These results suggest that the majority of the IMPs are indeed prestin and that electrically evoked length and stiffness changes are interrelated and dependent on both prestin and on the cortical actin cytoskeletal lattice of the OHC lateral membrane. Published (C) 2009 Wiley-Liss, Inc. C1 [He, David Z. Z.; Jia, Shuping] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA. [Zuo, Jian] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. [Sato, Takashi; Andrade, Leonardo P.; Riordan, Gavin P.; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD USA. RP Kachar, B (reprint author), NIDCD, NIH, 50 South Dr,Rm 4249, Bethesda, MD 20892 USA. EM hed@creighton.edu; kacharb@nidcd.nih.gov RI Andrade, Leonardo/C-9554-2011 OI Andrade, Leonardo/0000-0002-0004-5677 FU NIDCD; DIR; NIH [DC 004696, DC 06471] FX This work was supported by NIDCD, DIR, NIH (to B.K.), and NIH grants DC 004696 (to D.H.), and DC 06471 (to J.Z.). NR 50 TC 15 Z9 16 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1949-3584 J9 CYTOSKELETON JI Cytoskeleton PD JAN PY 2010 VL 67 IS 1 BP 43 EP 55 DI 10.1002/cm.20423 PG 13 WC Cell Biology SC Cell Biology GA 579AE UT WOS:000276337600005 PM 20169529 ER PT J AU Scheinberg, P AF Scheinberg, Phillip TI Immunosuppression or immunostimulation for aplastic anemia? A blast from the past SO CYTOTHERAPY LA English DT Editorial Material C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Room 3-5140,MSC 1202, Bethesda, MD 20892 USA. EM Scheinbp@nhlbi.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 NR 10 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2010 VL 12 IS 5 BP 574 EP 575 DI 10.3109/14653249.2010.507332 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 658EV UT WOS:000282474100001 PM 20735161 ER PT J AU Gee, AP Richman, S Durett, A McKenna, D Traverse, J Henry, T Fisk, D Pepine, C Bloom, J Willerson, J Prater, K Zhao, D Koc, JR Ellis, S Taylor, D Cogle, C Moye, L Simari, R Skarlatos, S AF Gee, Adrian P. Richman, Sara Durett, April McKenna, David Traverse, Jay Henry, Timothy Fisk, Diann Pepine, Carl Bloom, Jeannette Willerson, James Prater, Karen Zhao, David Koc, Jane Reese Ellis, Steven Taylor, Doris Cogle, Christopher Moye, Lemuel Simari, Robert Skarlatos, Sonia TI Multicenter cell processing for cardiovascular regenerative medicine applications: the Cardiovascular Cell Therapy Research Network (CCTRN) experience SO CYTOTHERAPY LA English DT Article DE cardiac cell therapy; cell therapy; multicenter trials; quality control; regenerative medicine; Sepax ID ACUTE MYOCARDIAL-INFARCTION; PROTOCOLS; REPAIR; TRIAL AB Background aims. Multicenter cellular therapy clinical trials require the establishment and implementation of standardized cell-processing protocols and associated quality control (QC) mechanisms. The aims here were to develop such an infrastructure in support of the Cardiovascular Cell Therapy Research Network (CCTRN) and to report on the results of processing for the first 60 patients. Methods. Standardized cell preparations, consisting of autologous bone marrow (BM) mononuclear cells, prepared using a Sepax device, were manufactured at each of the five processing facilities that supported the clinical treatment centers. Processing staff underwent centralized training that included proficiency evaluation. Quality was subsequently monitored by a central QC program that included product evaluation by the CCTRN biorepositories. Results. Data from the first 60 procedures demonstrated that uniform products, that met all release criteria, could be manufactured at all five sites within 7 h of receipt of BM. Uniformity was facilitated by use of automated systems (the Sepax for processing and the Endosafe device for endotoxin testing), standardized procedures and centralized QC. Conclusions. Complex multicenter cell therapy and regenerative medicine protocols can, where necessary, successfully utilize local processing facilities once an effective infrastructure is in place to provide training and QC. C1 [Gee, Adrian P.] Baylor Coll Med, Ctr Cell & Gene Therapy, Feigin Ctr, Houston, TX 77030 USA. [McKenna, David] Univ Minnesota, Mol & Cellular Therapeut Facil, St Paul, MN 55108 USA. [Traverse, Jay; Henry, Timothy] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Fisk, Diann; Cogle, Christopher] Univ Florida, Shands Hosp, Stem Cell Lab, Gainesville, FL USA. [Pepine, Carl] Univ Florida, Dept Med, Gainesville, FL USA. [Willerson, James] St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX USA. [Prater, Karen; Zhao, David] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Koc, Jane Reese] UHCMC Ireland Canc Ctr, Cell Therapy Serv, Cleveland, OH USA. [Ellis, Steven] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Taylor, Doris] Univ Minnesota, Ctr Cardiovasc Repair, Minneapolis, MN USA. [Moye, Lemuel] Univ Texas Sch Publ Hlth, Houston, TX USA. [Simari, Robert] Mayo Clin, Coll Med, Rochester, MN USA. [Skarlatos, Sonia] NHLBI, Bethesda, MD 20892 USA. RP Gee, AP (reprint author), Baylor Coll Med, Ctr Cell & Gene Therapy, Feigin Ctr, MC3-3320,102 Bates St, Houston, TX 77030 USA. RI Cogle, Christopher/H-1746-2016 OI Cogle, Christopher/0000-0001-5422-6863 FU NHLBI [U01-HL-087318, N01-HB-37164]; National Heart and Blood Institute [N01-HB-37163]; Department of Blood and Marrow Transplant at the MD Anderson Cancer Center, Houston, Texas FX This study was supported by grant number U01-HL-087318 from NHLBI It was also supported in part by NHLBI contract numbers N01-HB-37164 (Molecular and Cellular Therapeutics Facility, University of Minnesota) and N01-HB-37163 (Cell-processing facility, Baylor College of Medicine) from the National Heart and Blood Institute. Validation and qualification data on the use of the Sepax device were generated under a CCTRN subcontract by John McMannis PhD of the Department of Blood and Marrow Transplant at the MD Anderson Cancer Center, Houston, Texas. NR 13 TC 16 Z9 16 U1 0 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2010 VL 12 IS 5 BP 684 EP 691 DI 10.3109/14653249.2010.487900 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 658EV UT WOS:000282474100013 PM 20524773 ER PT S AU Tatusova, T AF Tatusova, Tatiana BE Carugo, O Eisenhaber, F TI Genomic Databases and Resources at the National Center for Biotechnology Information SO DATA MINING TECHNIQUES FOR THE LIFE SCIENCES SE Methods in Molecular Biology LA English DT Article; Book Chapter DE bioinformatics; genome; metagenome; database; data management system; sequence analysis ID SEQUENCE DATABASE; NCBI; ALIGNMENT; ARCHIVE; ENTREZ; MAIZE; BLAST; WHEAT; RICE AB The National Center for Biotechnology Information (NCBI), as a primary public repository of sequence data, collects and maintains enormous amounts Of heterogeneous data. Data for genomes, genes, gene expressions, gene variation, gene families, proteins, and protein domains are integrated with the analytical, search, and retrieval resources through the NCBI Web site. Entrez, a text-based search and retrieval system, provides a fist and easy way to navigate across diverse biological databases. Customized genomic BLAST enables sequence similarity searches against a special collection of organism-specific sequence data and viewing the resulting alignments within a genomic context Using NCBI's genome browser, Map Viewer. Comparative genome analysis tools lead to further Understanding Of evolutionary processes, quickening the pace of discovery. C1 NIH, Bethesda, MD 20892 USA. RP Tatusova, T (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 7 Z9 7 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 978-1-60327-240-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 609 BP 17 EP 44 DI 10.1007/978-1-60327-241-4_2 D2 10.1007/978-1-60327-241-4 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BMP89 UT WOS:000273303600002 PM 20221911 ER PT J AU Baxter, LL Moreland, RT Nguyen, AD Wolfsberg, TG Pavan, WJ AF Baxter, Laura L. Moreland, R. Travis Anh-Dao Nguyen Wolfsberg, Tyra G. Pavan, William J. TI A curated online resource for SOX10 and pigment cell molecular genetic pathways SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION LA English DT Article AB We describe the creation of a specialized web-accessible database named the Pigment Cell Gene Resource, which contains information on the genetic pathways that regulate pigment cell development and function. This manually curated database is comprised of two sections, an annotated literature section and an interactive transcriptional network diagram. Initially, this database focuses on the transcription factor SOX10, which has essential roles in pigment cell development and function, but the database has been designed with the capacity to expand in the future, allowing inclusion of many more pigmentation genes. C1 [Baxter, Laura L.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Moreland, R. Travis; Anh-Dao Nguyen; Wolfsberg, Tyra G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Pavan, WJ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM bpavan@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Funding for open access charge: Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 25 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1758-0463 J9 DATABASE-OXFORD JI Database PY 2010 AR baq025 DI 10.1093/database/baq025 PG 7 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA V21ER UT WOS:000208191400028 ER PT J AU Zamboni, G Grafman, J Krueger, F Knutson, KM Huey, ED AF Zamboni, G. Grafman, J. Krueger, F. Knutson, K. M. Huey, E. D. TI Anosognosia for Behavioral Disturbances in Frontotemporal Dementia and Corticobasal Syndrome: A Voxel-Based Morphometry Study SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Frontotemporal dementia; Corticobasal syndrome; Voxel-based morphometry; Anosognosia; Loss of insight; Frontal Systems Behavior Scale ID PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE; COGNITIVE DEFICITS; SELF-AWARENESS; PERSPECTIVE-TAKING; DEPRESSION; INSIGHT; DEGENERATION; PERSONALITY; IMPAIRMENT AB Background: Patients with syndromes of the frontotemporal dementia spectrum are frequently unaware of their behavioral changes. Methods: Seventy patients with a clinical diagnosis of behavioral variant frontotemporal dementia (bv-FTD, n = 27), aphasic variant frontotemporal dementia (a-FTD, n = 12) and corticobasal syndrome (CBS, n = 31) participated in the study. Anosognosia for behavioral disturbances was measured as discrepancy between caregiver's and patient's ratings on the Frontal Systems Behavior Scale for present and premorbid behavioral symptoms. Voxel-based morphometry analysis of MRI data was performed to explore the association between anosognosia and gray matter loss. Results: Although behavioral symptoms were reported in all the groups, the comparison between present and premorbid anosognosia revealed that bv-FTD patients not only underestimated their present behavioral disturbances compared to their caregivers, but also overestimated their premorbid behavioral disturbances. Across all groups, the degree of anosognosia for present behavioral impairment correlated with gray matter atrophy in a posterior region of the right superior temporal sulcus (adjacent to the temporoparietal junction). Conclusion: These results confirm the role of the right temporoparietal cortex in the genesis of anosognosia and suggest that, in clinical syndromes of the frontotemporal dementia spectrum, anosognosia is associated with the dysfunction of temporoparietal mechanisms of self versus others knowledge. Copyright (C) 2010 S. Karger AG, Basel C1 [Zamboni, G.; Grafman, J.; Krueger, F.; Knutson, K. M.; Huey, E. D.] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Huey, E. D.] Litwin Zucker Res Ctr Study Alzheimers Dis & Memo, Great Neck, NY USA. [Zamboni, G.] Univ Modena, I-41100 Modena, Italy. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Zamboni, Giovanna/F-3583-2017; OI Zamboni, Giovanna/0000-0002-6133-3373; Grafman, Jordan H./0000-0001-8645-4457; Knutson, Kristine/0000-0003-4626-4514 FU National Institutes of Health/the National Institute of Neurological Disorders and Stroke; Italian Ministry of University and Research FX We thank Michael Tierney, Alyson Cavanagh and Karen De Tucci for patient testing, the Clinical Center nurses for patient care, and Nicole Armstrong for assistance with data analysis. This study was supported by the intramural program of the National Institutes of Health/the National Institute of Neurological Disorders and Stroke (to all authors) and the Italian Ministry of University and Research (to G. Z.). NR 42 TC 22 Z9 22 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2010 VL 29 IS 1 BP 88 EP 96 DI 10.1159/000255141 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 562MB UT WOS:000275054000012 PM 20150729 ER PT B AU Day, M DeMulder, EK Stribling, SM AF Day, Monimalika DeMulder, Elizabeth K. Stribling, Stacia M. BE Salili, F Hoosain, R TI USING THE PROCESS OF CULTURAL RECEPROCITY TO CREATE MULTICULTURAL DEMOCRATIC CLASSROOMS SO DEMOCRACY AND MULTICULTURAL EDUCATION SE Research in Multicultural Education and International Perspectives LA English DT Article; Book Chapter AB Cultural reciprocity is a relationship-based process that has been used by special educators to develop collaborative relationships with families. In this chapter, we demonstrate the use of this process by general educators and the ways in which this process contributes to the development of multicultural democratic classrooms. We discuss each step of the process at length and provide examples of its application in the classroom. C1 [Day, Monimalika] George Mason Univ, Coll Educ & Human Dev, Fairfax, VA 22030 USA. [Day, Monimalika; DeMulder, Elizabeth K.] George Mason Univ, Initiat Educ Transformat, Fairfax, VA 22030 USA. [DeMulder, Elizabeth K.] NIMH, Bethesda, MD USA. [Stribling, Stacia M.] George Mason Univ, Grad Sch Educ, Masters New Profess Studies Teaching Program, Fairfax, VA 22030 USA. RP Day, M (reprint author), George Mason Univ, Coll Educ & Human Dev, Fairfax, VA 22030 USA. EM mday3@gmu.edu; edemulde@gmu.edu; sslawins@gmu.edu NR 26 TC 0 Z9 0 U1 0 U2 0 PU INFORMATION AGE PUBLISHING-IAP PI CHARLOTTE PA PO BOX 79049, CHARLOTTE, NC 28271-7047 USA BN 978-1-60752-422-9 J9 RES MULTICULT EDUC I PY 2010 BP 237 EP 262 PG 26 WC Education & Educational Research SC Education & Educational Research GA BOL22 UT WOS:000276930800010 ER PT J AU Suzman, R AF Suzman, Richard TI PROLOGUE: RESEARCH ON THE DEMOGRAPHY AND ECONOMICS OF AGING SO DEMOGRAPHY LA English DT Editorial Material C1 NIA, Div Behav & Social Res, Bethesda, MD 20892 USA. RP Suzman, R (reprint author), NIA, Div Behav & Social Res, NIH Gateway Bldg,Room 533,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM SuzmanR@nia.nih.gov NR 8 TC 1 Z9 1 U1 1 U2 1 PU POPULATION ASSOC AMER PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036 USA SN 0070-3370 J9 DEMOGRAPHY JI Demography PY 2010 VL 47 SU S BP S1 EP S4 PG 4 WC Demography SC Demography GA 686BL UT WOS:000284671700001 PM 21302427 ER PT S AU Durbin, AP Whitehead, SS AF Durbin, Anna P. Whitehead, Stephen S. BE Rothman, AL TI Dengue Vaccine Candidates in Development SO DENGUE VIRUS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID VIRUS ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODY-RESPONSE; TERMINALLY TRUNCATED DENGUE-2; TETRAVALENT DNA VACCINE; RHESUS LUNG-CELLS; ATTENUATED DENGUE; TYPE-2 VIRUS; IMMUNE-RESPONSES; JAPANESE ENCEPHALITIS; PROTECTIVE EFFICACY AB Each of the DENV serotypes can cause the full spectrum of dengue illness. Epidemiological studies have implicated preexisting heterotypic DENV antibody as a risk factor for more severe disease upon secondary DENV infection. For these reasons, a successful DENV vaccine must protect against all four DENV serotypes. Live attenuated DENV vaccine candidates are the furthest along in development and clinical evaluation. Two live attenuated tetravalent vaccine candidates are in Phase 2 clinical trials in DENV endemic regions. Numerous other vaccine candidates including inactivated whole virus, recombinant subunit protein, DNA and virus-vectored vaccines are also under development. Those DENV vaccine candidates that have been evaluated in preclinical animal models or in clinical trials will be discussed. C1 [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. [Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. EM adurbin@jhsph.edu; swhitehead@niaid.nih.gov NR 103 TC 60 Z9 62 U1 1 U2 11 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-02214-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2010 VL 338 BP 129 EP 143 DI 10.1007/978-3-642-02215-9_10 D2 10.1007/978-3-642-02215-9 PG 15 WC Immunology; Microbiology SC Immunology; Microbiology GA BMW93 UT WOS:000273776100010 PM 19802583 ER PT S AU Blaney, JE Durbin, AP Murphy, BR Whitehead, SS AF Blaney, Joseph E., Jr. Durbin, Anna P. Murphy, Brian R. Whitehead, Stephen S. BE Rothman, AL TI Targeted Mutagenesis as a Rational Approach to Dengue Virus Vaccine Development SO DENGUE VIRUS SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID HEALTHY ADULT VOLUNTEERS; LIVE-ATTENUATED VACCINE; 3' UNTRANSLATED REGION; RHESUS-MONKEYS; 3'-UNTRANSLATED REGION; ANTIBODY-RESPONSE; STRUCTURAL GENES; SERIAL PASSAGE; KIDNEY-CELLS; TYPE-4 VIRUS AB The recombinant dengue virus type 4 (rDEN4) vaccine candidate, rDEN4 Delta 30, was found to be highly infectious, immunogenic and safe in human volunteers. At the highest dose (10(5) PFU) evaluated in volunteers, 25% of the vaccinees had mild elevations in liver enzymes that were rarely seen at lower doses. Here, we describe the generation and selection of additional mutations that were introduced into rDEN4 Delta 30 to further attenuate the virus in animal models and ultimately human vaccinees. Based on the elevated liver enzymes associated with the 10(5) PFU dose of rDEN4 Delta 30 and the known involvement of liver infection in dengue virus pathogenesis, a large panel of mutant viruses was screened for level of replication in the HuH-7 human hepatoma cell line, a surrogate for human liver cells and selected viruses were further analyzed for level of viremia in SCID-HuH-7 mice. It was hypothesized that rDEN4 Delta 30 derivatives with restricted replication in vitro and in vivo in HuH-7 human liver cells would be restricted in replication in the liver of vaccinees. Two mutations identified by this screen, NS3 4995 and NS5 200,201, were separately introduced into rDEN4 Delta 30 and found to further attenuate the vaccine candidate for SCID-HuH-7 mice and rhesus monkeys while retaining sufficient immunogenicity in rhesus monkeys to confer protection. In humans, the rDEN4 Delta 30-200,201 vaccine candidate administered at 10(5) PFU exhibited greatly reduced viremia, high infectivity and lacked liver toxicity while inducing serum neutralizing antibody at a level. comparable to that observed in volunteers immunized with rDEN4 Delta 30. Clinical studies of rDEN4 Delta 30-4995 are ongoing. C1 [Blaney, Joseph E., Jr.; Murphy, Brian R.; Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, NIH, 33 North Dr,Room 3W10A, Bethesda, MD 20892 USA. EM adurbin@jhsph.edu; swhitehead@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000891-07, Z01 AI000891-08] NR 48 TC 11 Z9 11 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-02214-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2010 VL 338 BP 145 EP 158 DI 10.1007/978-3-642-02215-9_11 D2 10.1007/978-3-642-02215-9 PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA BMW93 UT WOS:000273776100011 PM 19802584 ER PT S AU Nordstrom, RJ AF Nordstrom, Robert J. BE Nordstrom, RJ TI The Need for Validation Standards in Medical Imaging SO DESIGN AND PERFORMANCE VALIDATION OF PHANTOMS USED IN CONJUNCTION WITH OPTICAL MEASUREMENT OF TISSUE II SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Design and Performance Validation of Phantoms Used in Conjunction with Optical Measurements of Tissue II CY JAN 23, 2010 CL San Francisco, CA SP SPIE AB Validation of imaging technologies is becoming increasingly important as imaging begins to take a role as a biomarker. Activities such as drug development, guided intervention, patient stratification, and therapy response assessment rely on very high measurements of sensitivity and specificity at the earliest possible time point. Imaging is capable of providing those measurements, but without validation of the results, clinical acceptance will be delayed. It must be pointed out, however, that validation is different from verification, and the role of phantoms is different for these two operations. This paper discusses the need for multiple phantoms in the role of validation in order to present optical imaging devices with the extremes of tissue states expected in real-world operation. C1 NCI, Bethesda, MD 20892 USA. RP Nordstrom, RJ (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 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 978-0-8194-7963-1 J9 PROC SPIE PY 2010 VL 7567 AR 756702 DI 10.1117/12.845508 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSG35 UT WOS:000284364900001 ER PT J AU Andersson, E Bryjova, L Biris, K Yamaguchi, TP Arenas, E Bryja, V AF Andersson, Emma Bryjova, Lenka Biris, Kristin Yamaguchi, Terry P. Arenas, Ernest Bryja, Vitezslav TI Genetic Interaction Between Lrp6 and Wnt5a During Mouse Development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Wnt5a; Lrp6; somitogenesis; development ID NEURAL-TUBE CLOSURE; WNT/BETA-CATENIN; DISHEVELLED PHOSPHORYLATION; CONVERGENT EXTENSION; DOPAMINERGIC CELLS; IN-VIVO; WNT-5A; MICE; POLARITY; PATHWAY AB Lrp6 is generally described as a receptor required for signal transduction in the Wnt/beta-catenin pathway. Wnt5a, however, is a Wnt ligand that usually does not activate Wnt/beta-catenin but rather activates noncanonical Wnt signaling. We have previously shown that Lrp6 can inhibit noncanonical Wnt5a/Wnt11 signaling and that Lrp5/6 loss-of-function produces noncanonical gain-of function defects, which can be rescued by loss of Wnt5a. Here, we describe other phenotypes found in Wnt5a/Lrp6 compound mutant mice, including a worsening of individual Wnt5a or Lrp6 loss of function phenotypes. Lrp6 haploinsufficiency in a Wnt5a-/- background caused spina bifida and exacerbated posterior truncation. Wnt5a-/-Lrp6-/-embryos displayed presomitic mesoderm morphogenesis, somitogenesis, and neurogenesis defects, which are much more severe than in either of the single mutants. Interestingly these results reveal a further level of complexity in processes in which Wnt5a and LRP6 cooperate, or oppose each other, during mouse development. Developmental Dynamics 239:237-245, 2010. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Bryjova, Lenka; Bryja, Vitezslav] Masaryk Univ, Fac Sci, Inst Expt Biol, CS-61137 Brno, Czech Republic. [Bryjova, Lenka; Bryja, Vitezslav] Acad Sci Czech Republic, Inst Biophys, Dept Cytokinet, CS-61265 Brno, Czech Republic. [Andersson, Emma; Bryjova, Lenka; Arenas, Ernest; Bryja, Vitezslav] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden. [Biris, Kristin; Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RP Bryja, V (reprint author), Masaryk Univ, Fac Sci, Inst Expt Biol, Kotlarska 2, CS-61137 Brno, Czech Republic. EM Ernest.Arenas@ki.se; bryja@sci.muni.cz RI Bryja, Vit?zslav/H-1925-2014; Andersson, Emma/J-4236-2012; OI Bryja, Vit?zslav/0000-0002-9136-5085; Andersson, Emma/0000-0002-8608-625X; Arenas, Ernest/0000-0003-0197-6577 FU EMBO; Ministry of Education Youth and Sports of the Czech Republic [MSM 0021622430]; Swedish Foundation for Strategic Research; Swedish Research Council [VR2008:2811, DBRM]; Norwegian Research Council; Karolinska Institutet; Michael J. Fox Foundation; European Commission FX Grant sponsor: EMBO; Ministry of Education Youth and Sports of the Czech Republic; Grant number: MSM 0021622430; Grant sponsor: Swedish Foundation for Strategic Research (INGVAR and CEDB); Swedish Research Council; Grant number: VR2008:2811 and DBRM; Grant sponsor: Norwegian Research Council; Grant sponsor: Karolinska Institutet; Grant sponsor: Michael J. Fox Foundation; Grant sponsor: European Commission (Eurostemcell). NR 37 TC 19 Z9 19 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JAN PY 2010 VL 239 IS 1 SI SI BP 237 EP 245 DI 10.1002/dvdy.22101 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 545AM UT WOS:000273703900021 PM 19795512 ER PT J AU Paukner, A Huntsberry, ME Suomi, SJ AF Paukner, Annika Huntsberry, Mary E. Suomi, Stephen J. TI Visual Discrimination of Male and Female Faces by Infant Rhesus Macaques SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE Macaca mulatta; visual preferences; face perception ID MONKEYS; PREFERENCE; RESPONSES; RECOGNITION; 1ST AB Recent studies have revealed that human infants process female faces differently from male faces. To test whether a similar preference for female faces exists in other primates, we presented nursery-reared infant rhesus macaques with photographs of macaque faces and human faces. At <1 month old, infant macaques preferentially oriented towards female macaque faces when faces were presented upright. No preference for female human faces was found. At 9 months old, infants failed to show a visual preference for female macaque faces or female human faces, although they showed significantly more lipsmacking responses at female human faces. Compared to human infants, macaques appear to have stronger predispositions early in life but this preference may nonetheless be amendable to experience. Understanding how innate predispositions and the social rearing environment shape infants' understanding of faces remain important issues to be explored in order to understand facial processing abilities in humans and other primates. (C) 2009 Wiley Periodicals, Inc. Dev Psychobiol 52: 54-61, 2010. C1 [Paukner, Annika; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20837 USA. [Huntsberry, Mary E.] NIH, Div Vet Resources, ORS, DHHS, Bethesda, MD 20892 USA. [Huntsberry, Mary E.] SoBran Inc, Bethesda, MD USA. RP Paukner, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Anim Ctr, POB 529, Poolesville, MD 20837 USA. EM pauknera@mail.nih.gov FU Division of Intramural Research, NICHD FX We thank Sarah Unbehagen, Lisa Darcey, and Angela Ruggiero for help in collecting the data. Human face stimuli came from the PICS image archive, Stirling University, UK (http://pics.stir. ac.uk). This study was supported by the Division of Intramural Research, NICHD. NR 19 TC 7 Z9 7 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD JAN PY 2010 VL 52 IS 1 BP 54 EP 61 DI 10.1002/dev.20412 PG 8 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 543ZW UT WOS:000273621700006 PM 19937740 ER PT J AU Cheng, S Massaro, JM Fox, CS Larson, MG Keyes, MJ McCabe, EL Robins, SJ O'Donnell, CJ Hoffmann, U Jacques, PF Booth, SL Vasan, RS Wolf, M Wang, TJ AF Cheng, Susan Massaro, Joseph M. Fox, Caroline S. Larson, Martin G. Keyes, Michelle J. McCabe, Elizabeth L. Robins, Sander J. O'Donnell, Christopher J. Hoffmann, Udo Jacques, Paul F. Booth, Sarah L. Vasan, Ramachandran S. Wolf, Myles Wang, Thomas J. TI Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study SO DIABETES LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; METABOLIC SYNDROME; INSULIN SENSITIVITY; BODY-FAT; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; HYPOVITAMINOSIS-D; TISSUE VOLUMES AB OBJECTIVE-Because vitamin D deficiency is associated with a variety of chronic diseases, understanding the characteristics that promote vitamin D deficiency in otherwise healthy adults could have important clinical implications. Few studies relating vitamin D deficiency to obesity have included direct measures of adiposity. Furthermore, the degree to which vitamin D is associated with metabolic traits after adjusting for adiposity measures is unclear. RESEARCH DESIGN AND METHODS-We investigated the relations of serum 25-hydroxyvitamin D (25[OH]D) concentrations with indexes of cardiometabolic risk in 3,890 nondiabetic individuals; 1,882 had subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes measured by multidetector computed tomography (CT). RESULTS-In multivariable-adjusted regression models, 25(OH)D was inversely associated with winter season, waist circumference, and serum insulin (P < 0.005 for all). In models further adjusted for CT measures, 25(OH)D was inversely related to SAT (-1.1 ng/ml per SD increment in SAT, P = 0.016) and VAT (-2.3 ng/ml per SD, P < 0.0001). The association of 25(OH)D with insulin resistance measures became nonsignificant after adjustment for VAT. Higher adiposity volumes were correlated with lower 25(OH)D across different categories of BMI, including in lean individuals (BMI <25 kg/m(2)). The prevalence of Vitamin D deficiency (25[OH]D <20 ng/ml) was threefold higher in those with high SAT and high VAT than in those with low SAT and low VAT (P < 0.0001). CONCLUSIONS-Vitamin D status is strongly associated with variation in subcutaneous and especially visceral adiposity. The mechanisms by which adiposity promotes vitamin D deficiency warrant further study. Diabetes 59:242-248, 2010 C1 [Cheng, Susan; Massaro, Joseph M.; Fox, Caroline S.; Larson, Martin G.; Keyes, Michelle J.; McCabe, Elizabeth L.; Robins, Sander J.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan; McCabe, Elizabeth L.; O'Donnell, Christopher J.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Dept Med,Med Sch, Boston, MA 02115 USA. [Cheng, Susan] Harvard Univ, Beth Israel Deaconess Med Ctr, Clin Investigator Training Program, Sch Med, Boston, MA 02215 USA. [Massaro, Joseph M.; Larson, Martin G.; Keyes, Michelle J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Dept Med,Med Sch, Boston, MA 02115 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Jacques, Paul F.; Booth, Sarah L.] Tufts Univ, Human Nutr Res Ctr Aging, Nutrit Epidemiol Program, Jean Mayer USDA, Boston, MA 02111 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA. RP Wang, TJ (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA. EM tjwang@partners.org OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-25195, R01-DK-80739]; American Heart Association FX This work was supported in part by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) contract N01-HC-25195, R01-DK-80739, and a grant from the American Heart Association.; M.W. has received honoraria for educational presentations from Abbott Laboratories. T.J.W. has served on the scientific advisory board for DiaSorin. No other potential conflicts of interest relevant to this article were reported.; We thank Karol Pencina, MS, for assistance with statistical analyses. NR 51 TC 205 Z9 215 U1 3 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2010 VL 59 IS 1 BP 242 EP 248 DI 10.2337/db09-1011 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 542DS UT WOS:000273472500031 PM 19833894 ER PT J AU Xu, Q Song, YQ Hollenbeck, A Blair, A Schatzkin, A Chen, HL AF Xu, Qun Song, Yiqing Hollenbeck, Albert Blair, Aaron Schatzkin, Arthur Chen, Honglei TI Day Napping and Short Night Sleeping Are Associated With Higher Risk of Diabetes in Older Adults SO DIABETES CARE LA English DT Article ID EXCESSIVE DAYTIME SLEEPINESS; SELF-REPORTED SLEEP; LARGE COHORT; DURATION; POPULATION; MORTALITY; HEALTH; DEPRESSION; COMMUNITY; QUALITY AB OBJECTIVE - To examine whether day napping or short night sleeping is associated with higher risk of diabetes. RESEARCH DESIGN AND METHODS - This was a prospective study of hours of day napping and night sleeping assessed in 1996-1997 in relation to diabetes diagnosed between 2000 and 2006 (n = 10,143) among 174,542 participants in the National Institutes of Health (NIH)-AARP Diet and Health Study. Odds ratios (ORs) and 95% CI were derived from multivariate logistic regression models. RESULTS - Longer day napping Was associated with a higher risk of diabetes. After adjustment for potential confounders, ORs were 1.23(95% CI 1.18-1.29) for those reporting <1 h and 1.55 (95% CI 1.45-1.66) for those reporting >= 1 h of napping compared with individuals who did not nap (P(trend) < 0.0001). For night sleeping, with 7-8 h as the referent, the OR was 1.46 (95% CI 1.31-1.63) for <5 h, 1.11 (1.06-1.16) for 5-6 h, and 1.11 (0.99-1.24) for >= 9 h. In both analyses, additional adjustment for BMI only modestly attenuated the associations. Further analysis showed a statistically significant interaction between hours of napping and sleeping on diabetes (P(interaction) < 0.0001). Among participants With no napping, only short night sleeping was associated with higher occurrence of diabetes, whereas among those with >= 1 h of napping, both long and short sleeping was associated with higher risk. CONCLUSIONS - Day napping and short night sleeping are associated with higher risk of diabetes. The association between sleep duration and diabetes may be modified by napping habit. C1 [Xu, Qun; Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Song, Yiqing] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA. [Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Rockville, MD USA. RP Chen, HL (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779 FU NIH; National Institute of Environmental Health Sciences [Z01-ES-101986]; National Cancer Institute [Z01-CP-010196-02] FX This study was supported by the Intramural Research Program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986) and the National Cancer Institute (Z01-CP-010196-02).; No Potential conflicts of interest relevant to this article were reported.; We are grateful for the continuous contribution of the NIH-AARP Diet and Health Study participants. NR 25 TC 55 Z9 60 U1 2 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2010 VL 33 IS 1 BP 78 EP 83 DI 10.2337/dc09-1143 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 544AA UT WOS:000273622200016 PM 19825823 ER PT J AU Staten, MA Stern, MP Miller, WG Steffes, MW Campbell, SE AF Staten, Myrlene A. Stern, Michael P. Miller, W. Greg Steffes, Michael W. Campbell, Scott E. CA Insulin Standardization Workgrp TI Insulin Assay Standardization Leading to measures of insulin sensitivity and secretion for practical clinical care SO DIABETES CARE LA English DT Editorial Material ID GLUCOSE-TOLERANCE; DIABETES-MELLITUS; RESISTANCE; IMMUNOASSAYS; DYSFUNCTION C1 [Staten, Myrlene A.] NIDDK, NIH, Bethesda, MD 20892 USA. [Stern, Michael P.] Univ Texas Hlth Sci Ctr San Antonio, Div Clin Epidemiol, Dept Med, San Antonio, TX 78229 USA. [Miller, W. Greg] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA USA. [Steffes, Michael W.] Univ Minnesota, Dept Lab Med & Pathol, Sch Med, Minneapolis, MN 55455 USA. [Campbell, Scott E.] Amer Diabet Assoc, Alexandria, VA USA. RP Staten, MA (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM statenm@niddk.nih.gov NR 13 TC 32 Z9 33 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2010 VL 33 IS 1 BP 205 EP 206 DI 10.2337/dc09-1206 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 544AA UT WOS:000273622200042 PM 20040676 ER PT S AU Stranahan, AM Mattson, MP AF Stranahan, Alexis M. Mattson, Mark P. BE Craft, S Christen, Y TI Stress Hormones and Neuroplasticity in the Diabetic Brain SO DIABETES, INSULIN AND ALZHEIMER'S DISEASE SE Research and Perspectives in Alzheimers Disease LA English DT Proceedings Paper CT 24th Symposium on Medicine and Research of Alzhemers Disease CY APR 06, 2009 CL Fondat IPSEN, Paris, FRANCE HO Fondat IPSEN ID LONG-TERM POTENTIATION; HIPPOCAMPAL SYNAPTIC PLASTICITY; OBESE ZUCKER RATS; CORTICOTROPIN-RELEASING-FACTOR; TRANSGENIC MOUSE MODEL; HEALTHY ELDERLY-MEN; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; DENTATE GYRUS; INSULIN-RESISTANCE AB Diabetes is associated with metabolic dysfunction across multiple organ systems, and the central nervous system is no exception. Neurons in the diabetic brain exhibit functional alterations that may increase the risk of cognitive decline and Alzheimer's disease. Diabetes is associated with changes in the hypothalamic-pituitary-adrenal (HPA) axis, but the relationship between HPA axis function and cognitive dysfunction in diabetes is still being elucidated. Here we review evidence for and against HPA axis dysfunction in diabetes, and its consequences for neuroplasticity in the hippocampus, a brain region that mediates certain aspects of learning and memory. The tripartite relationship between diabetes, HPA axis alterations, and cognitive impairment will be discussed. The evidence favors a role for adrenal steroid hormones as central and peripheral mediators of diabetes-induced cellular dysfunction. In the hippocampus, adrenal corticosteroids may perturb neurotrophic factor signaling, resulting in impaired neurogenesis, synaptic plasticity and cognitive function. The adverse effects of diabetes on hippocampal plasticity may be allayed by exercise and dietary energy restriction. C1 [Stranahan, Alexis M.; Mattson, Mark P.] NIA, NIH, Biomed Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RP Stranahan, AM (reprint author), NIA, NIH, Biomed Res Ctr, Neurosci Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM alexis.stranahan@jhu.edu NR 96 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6066 BN 978-3-642-04299-7 J9 RES PER ALZ PY 2010 BP 57 EP 71 DI 10.1007/978-3-642-04300-0_4 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BQS18 UT WOS:000281692500004 ER PT S AU Launer, LJ AF Launer, Lenore J. BE Craft, S Christen, Y TI Diabetes and the Brain - An Epidemiologic Perspective SO DIABETES, INSULIN AND ALZHEIMER'S DISEASE SE Research and Perspectives in Alzheimers Disease LA English DT Proceedings Paper CT 24th Symposium on Medicine and Research of Alzhemers Disease CY APR 06, 2009 CL Fondat IPSEN, Paris, FRANCE HO Fondat IPSEN ID GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK; AMERICAN-HEART-ASSOCIATION; POPULATION-BASED COHORT; MIDLIFE BLOOD-PRESSURE; COGNITIVE IMPAIRMENT; ALZHEIMER-DISEASE; SCIENTIFIC STATEMENT; APOE EPSILON-4; RISK-FACTORS; ELDERLY-MEN AB Type 2 diabetes (T2D) and cognitive impairment are two of the most common chronic conditions found in persons 60 years and older. After that age, studies suggest approximately 18%-20% of older persons have diabetes (Harris et al. 1988), about 19% are mildly cognitively impaired (MCI) in multiple domains (Lopez et al. 2003), and about 6% of community dwelling individuals have some dementia (Lobo et al. 2000). The prevalence of MCI and dementia increases with age as does the prevalence of diabetes; there is also an alarming trend towards a younger age of diabetes onset (Chaturvedi 2007). Several lines of investigation suggest a link between diabetes and disorders of cognitive function. Thus, the age-related trends in diabetes and cognitive disorders indicate there may be an even greater increase in the number of persons with MCI and dementia, in excess of the increase that is expected based on the age structure of the population. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, Gateway Bldg,3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov NR 44 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6066 BN 978-3-642-04299-7 J9 RES PER ALZ PY 2010 BP 73 EP 80 DI 10.1007/978-3-642-04300-0_5 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BQS18 UT WOS:000281692500005 ER PT J AU Chong, AY Lupsa, BC Cochran, EK Gorden, P AF Chong, A. Y. Lupsa, B. C. Cochran, E. K. Gorden, P. TI Efficacy of leptin therapy in the different forms of human lipodystrophy SO DIABETOLOGIA LA English DT Article DE Diabetes; Insulin resistance; Leptin; Lipodystrophy ID REVERSES INSULIN-RESISTANCE; LONG-TERM EFFICACY; GENERALIZED LIPODYSTROPHY; REPLACEMENT THERAPY; RECOMBINANT LEPTIN; CONGENITAL LIPODYSTROPHY; METABOLIC-REGULATION; LIPOATROPHY; DEFICIENCY; PATHWAYS AB Lipodystrophy is a rare disorder characterised by loss of adipose tissue, hypoleptinaemia, severe insulin resistance, diabetes and dyslipidaemia. The aims of this study were to determine whether leptin replacement in lipodystrophy patients ameliorates their metabolic abnormalities over an extended period of time and whether leptin therapy is effective in the different forms of lipodystrophy. We conducted an open-label prospective study of patients with acquired forms of lipodystrophy and inherited forms of lipodystrophy secondary to mutations in the AGPAT2, SEIPIN (also known as BSCL2), LMNA and PPAR gamma (also known as PPARG) genes. Between July 2000 and November 2008, 48 patients with lipodystrophy were treated with s.c. recombinant methionyl human leptin. Serum triacylglycerol and HbA(1c) levels declined dramatically with leptin therapy. Among 35 patients with data at baseline and 12 months, serum triacylglycerol fell by 59% (from 10.18 +/- 2.67 mmol/l to 4.16 +/- 0.99 mmol/l [means +/- SE]; p = 0.008) and HbA(1c) decreased by 1.5 percentage points (from 8.4 +/- 0.3% to 6.9 +/- 0.3%; p < 0.001). A significant reduction was seen in total cholesterol and a trend towards reduction was observed in LDL-cholesterol at 12 months. HDL-cholesterol was unchanged. Among generalised lipodystrophy patients, proteinuria diminished with leptin replacement. Patients with both acquired and inherited forms of lipodystrophy experienced decreases in serum triacylglycerol and HbA(1c) levels. Leptin replacement in lipodystrophy patients leads to significant and sustained improvements in glycaemic control and dyslipidaemia. Leptin is effective in the various forms of lipodystrophy, whether they are acquired or inherited, generalised or partial. ClinicalTrials.gov ID NCT00025883 This work was supported by intramural research funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). C1 [Chong, A. Y.; Lupsa, B. C.; Cochran, E. K.; Gorden, P.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Gorden, P (reprint author), NIDDK, Clin Endocrinol Branch, NIH, 10 Ctr Dr,CRC Room 6-5940, Bethesda, MD 20892 USA. EM PhillipG@intra.niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) FX This work was supported by intramural research funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). We are indebted to N. Siebring (NIDDK) for advice on nutrition, as well as to the nursing staff of the NIH Clinical Center and the fellows of the NIH Inter-institute Endocrine Training Program for patient care. We are grateful to R. Copeland for his technical assistance. We would also like to thank Amgen and Amylin Pharmaceuticals for generously providing r-metHuLeptin. NR 33 TC 76 Z9 83 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2010 VL 53 IS 1 BP 27 EP 35 DI 10.1007/s00125-009-1502-9 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 529PV UT WOS:000272530600005 PM 19727665 ER PT B AU Menon, S Jain, S Nagpal, R Kumar, M Mohania, D Yadav, D Marotta, F Yadav, M Yadav, H AF Menon, Saji Jain, Shalini Nagpal, Ravinder Kumar, Manoj Mohania, Dheeraj Yadav, Dhananjay Marotta, Fracesco Yadav, Mukesh Yadav, Hariom BE Watson, RR Zibadi, S Preedy, VR TI Immunomodulatory Potential of Conjugated Linolenic Acid SO DIETARY COMPONENTS AND IMMUNE FUNCTION SE Nutrition and Health Series LA English DT Article; Book Chapter DE Conjugate linolenic acid; immune system; nutrition; dietary component; functional foods ID TUMOR-NECROSIS-FACTOR; UNSATURATED FATTY-ACIDS; LACTATING DAIRY-COWS; PROSTAGLANDIN E-2; FACTOR-ALPHA; CYTOKINE PRODUCTION; LIPID-PEROXIDATION; GROWTH DEPRESSION; IMMUNE-RESPONSE; MICE C1 [Menon, Saji] Birla Inst Sci Res, Dept Biotechnol & Bioinformat, Jaipur, Rajasthan, India. [Mohania, Dheeraj] Natl Dairy Res Inst, Anim Biochem Div, Karnal 132001, Haryana, India. [Nagpal, Ravinder] Lovely Profess Univ, Sch Sci & Technol, Dept Biotechnol, Phagwara, Punjab, India. [Jain, Shalini] NIDDKD, NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA. [Kumar, Manoj] Natl Dairy Res Inst, Dairy Microbiol Div, Karnal 132001, Haryana, India. [Marotta, Fracesco] S Giuseppe Hosital, NEmergency Unit, Milan, Italy. [Yadav, Dhananjay] Jiwaji Univ, Sch Studies Biochem, Gwalior, Madhya Pradesh, India. [Yadav, Hariom] NIDDK, NIH, Clin Res Ctr, Diabet Branch, Bethesda, MD 20892 USA. [Yadav, Mukesh] Coll Adv Studies, Dept Biotechnol, Datia, Madhya Pradesh, India. RP Menon, S (reprint author), Birla Inst Sci Res, Dept Biotechnol & Bioinformat, Jaipur, Rajasthan, India. EM yadavh@mail.nih.gov NR 62 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 978-1-60761-060-1 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 217 EP 226 DI 10.1007/978-1-60761-061-8_12 D2 10.1007/978-1-60761-061-8 PG 10 WC Immunology; Nutrition & Dietetics SC Immunology; Nutrition & Dietetics GA BQK34 UT WOS:000281202700012 ER PT B AU Chen, X AF Chen, Xin BE Watson, RR Zibadi, S Preedy, VR TI Maturation and Activation of Dendritic Cells by Botanicals Used in Traditional Chinese Medicine: Role in Immune Enhancement SO DIETARY COMPONENTS AND IMMUNE FUNCTION SE Nutrition and Health Series LA English DT Article; Book Chapter DE Immunology; dendritic cells; traditional chinese medicine; polysaccharide; host resistance ID POLYSACCHARIDE-PROTEIN COMPLEX; JAPANESE HERBAL MEDICINE; BLOOD MONONUCLEAR-CELLS; LYCIUM-BARBARUM POLYSACCHARIDES; NECROSIS-FACTOR-ALPHA; HOCHU-EKKI-TO; YI-QI-TANG; NF-KAPPA-B; GANODERMA-LUCIDUM; REISHI POLYSACCHARIDES C1 NCI, SAIC Frederick Inc, Mol Immunoregulat Lab, Basic Res Program,Canc Inflammat Program,CCR, Frederick, MD 21702 USA. RP Chen, X (reprint author), NCI, SAIC Frederick Inc, Mol Immunoregulat Lab, Basic Res Program,Canc Inflammat Program,CCR, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA. EM chenxin@mail.nih.gov RI Chen, Xin/I-6601-2015 OI Chen, Xin/0000-0002-2628-4027 NR 85 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 978-1-60761-060-1 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 497 EP 514 DI 10.1007/978-1-60761-061-8_26 D2 10.1007/978-1-60761-061-8 PG 18 WC Immunology; Nutrition & Dietetics SC Immunology; Nutrition & Dietetics GA BQK34 UT WOS:000281202700026 ER PT J AU Koh, C Hipp, JD Kleiner, DE Heller, T AF Koh, C. Hipp, J. D. Kleiner, D. E. Heller, T. TI Acute right upper quadrant pain: A lesson in odds SO DIGESTIVE AND LIVER DISEASE LA English DT Letter ID LIVER-BIOPSY C1 [Koh, C.; Heller, T.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Hipp, J. D.; Kleiner, D. E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Koh, C (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA. EM Kohchris@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS [Z01 BC010686-03, Z01 DK075008-02, Z99 DK999999] NR 3 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD JAN PY 2010 VL 42 IS 1 BP 72 EP 73 DI 10.1016/j.dld.2009.05.004 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 576FU UT WOS:000276130500015 PM 19515620 ER PT J AU Korangy, F Hochst, B Manns, MP Greten, TF AF Korangy, Firouzeh Hoechst, Bastian Manns, Michael P. Greten, Tim F. TI Immune Responses in Hepatocellular Carcinoma SO DIGESTIVE DISEASES LA English DT Article; Proceedings Paper CT Falk Workshop on Immunology and Liver Disease/Falk Symposium 171 on Liver and Metabolic Syndrome CY OCT 15-18, 2009 CL Hannover, GERMANY DE Hepatocellular carcinoma; Cytotoxic therapy; Antigen-specific T cell response ID REGULATORY T-CELLS; TUMOR-IMMUNITY; ALPHA-FETOPROTEIN; PERIPHERAL-BLOOD; NKT CELLS; CANCER; IMMUNOTHERAPY; ANTIGENS; SURVIVAL; PEPTIDE AB Hepatocellular carcinoma (HCC) represents the third most common cause of cancer-related deaths worldwide and efficient treatment options are urgently needed. Based on its pathogenesis as well as a number of correlative studies, immunotherapy represents a potential therapeutic option for patients with HCC. However, tumors have also evolved numerous immune escape mechanisms, such as the generation of cells with immune suppressor functions, including regulatory T cells and myeloid-derived suppressor cells. It has been shown that these suppressor cells mask tumor-specific immune responses in patients with HCC. We propose that targeting suppressor cells either alone or in combination with conventional immunotherapy should be further evaluated in HCC patients. Copyright (C) 2010 S. Karger AG, Basel C1 [Korangy, Firouzeh; Hoechst, Bastian; Manns, Michael P.; Greten, Tim F.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany. [Korangy, Firouzeh; Hoechst, Bastian; Greten, Tim F.] Twincore Ctr Expt & Clin Res, Hannover, Germany. RP Greten, TF (reprint author), NCI, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM gretentf@mail.nih.gov RI Greten, Tim/B-3127-2015 OI Greten, Tim/0000-0002-0806-2535 NR 42 TC 22 Z9 29 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2010 VL 28 IS 1 BP 150 EP 154 DI 10.1159/000282079 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 594YY UT WOS:000277578800021 PM 20460904 ER PT J AU Singer, MV Zakhari, S McClain, C Dooley, S AF Singer, Manfred V. Zakhari, Sam McClain, Craig Dooley, Steven TI Liver and Pancreatic Diseases: Consequences of Chronic Alcoholic Consumption Preface SO DIGESTIVE DISEASES LA English DT Editorial Material C1 [Singer, Manfred V.; Dooley, Steven] Univ Heidelberg, Heidelberg, Germany. [Zakhari, Sam] NIAAA, Bethesda, MD USA. [McClain, Craig] Univ Louisville, Louisville, KY 40292 USA. RP Singer, MV (reprint author), Univ Heidelberg, Heidelberg, Germany. FU NIAAA NIH HHS [R01 AA018869, R01 AA018016] NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2010 VL 28 IS 6 BP 701 EP 701 DI 10.1159/000324275 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 757ND UT WOS:000290093200001 PM 21525752 ER PT J AU Su, HC AF Su, Helen C. TI Combined immunodeficiency associated with DOCK8 mutations and related immunodeficiencies SO DISEASE MARKERS LA English DT Editorial Material C1 [Su, Helen C.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Su, HC (reprint author), Bldg 10CRC,Room 5W3940,10CRC Ctr Dr,MSC 1456, Bethesda, MD 20892 USA. EM hsu@niaid.nih.gov RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 FU Intramural NIH HHS NR 0 TC 3 Z9 3 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2010 VL 29 IS 3-4 BP 121 EP 122 DI 10.3233/DMA-2010-0751 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 696RF UT WOS:000285458400001 PM 21178270 ER PT J AU Freeman, AF Holland, SM AF Freeman, Alexandra F. Holland, Steven M. TI Clinical manifestations of hyper IgE syndromes SO DISEASE MARKERS LA English DT Article ID HYPERIMMUNOGLOBULIN-E SYNDROME; RECURRENT INFECTION SYNDROME; CORONARY-ARTERY ANEURYSMS; JOBS-SYNDROME; COMBINED IMMUNODEFICIENCY; CRANIAL SYNOSTOSIS; SIGNAL TRANSDUCER; STAT3 MUTATIONS; T-CELLS; PATIENT AB Over the last 4 years, three genetic etiologies of hyper IgE syndromes have been identified: STAT3, DOCK8, and Tyk2. All of these hyper IgE syndromes are characterized by eczema, sinopulmonary infections, and greatly elevated serum IgE. However, each has distinct clinical manifestations. Mutations in STAT3 cause autosomal dominant HIES ( Job's syndrome), which is unique in its diversity of connective tissue, skeletal, and vascular abnormalities. DOCK8 deficiency is characterized by severe cutaneous viral infections such as warts, and a predisposition to malignancies at a young age. Only one individual has been identified with a hyper IgE phenotype associated with Tyk2 deficiency, which is characterized by nontuberculous mycobacterial infection. The identification of these genetic etiologies is leading to advances in understanding the pathogenesis of these syndromes with the goal of improving treatment. C1 [Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Freeman, AF (reprint author), NIH Bldg 10,Room 11N234, Bethesda, MD 20892 USA. EM freemaal@mail.nih.gov FU NIH, NIAID, Bethesda, MD [20892] FX This research was supported by the Intramural Research Program of the NIH, NIAID, Bethesda, MD 20892. The views expressed in this article are those of the authors and do not reflect the official policy of the U.S. Government. NR 50 TC 38 Z9 43 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2010 VL 29 IS 3-4 BP 123 EP 130 DI 10.3233/DMA-2010-0734 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 696RF UT WOS:000285458400002 PM 21178271 ER PT J AU Zhang, QA Davis, JC Dove, CG Su, HC AF Zhang, Qian Davis, Jeremiah C. Dove, Christopher G. Su, Helen C. TI Genetic, clinical, and laboratory markers for DOCK8 immunodeficiency syndrome SO DISEASE MARKERS LA English DT Article DE DOCK8; DIDS; combined immunodeficiency; hyper-IgE syndrome; atopic dermatitis; cutaneous viral infections; lymphopenia ID HYPER-IGE SYNDROME; WISKOTT-ALDRICH-SYNDROME; COPY NUMBER POLYMORPHISM; ATOPIC-DERMATITIS; HUMAN GENOME; T-CELL; HERPES-SIMPLEX; RHO-GTPASES; HOMOZYGOUS DELETIONS; RAC ACTIVATOR AB DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy, and early onset malignancy. Genetic studies revealed large, unique deletions in patients from different families and ethnic backgrounds. Clinical markers of DIDS include atopic dermatitis, allergies, cutaneous viral infections, recurrent respiratory tract infections, and malignancy. Immune assessments showed T cell lymphopenia, hyper-IgE, hypo-IgM, and eosinophilia. The impaired lymphocyte functions in DIDS patients appear central for disease pathogenesis. C1 [Zhang, Qian; Dove, Christopher G.; Su, Helen C.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Davis, Jeremiah C.] Univ Washington, Seattle Childrens Hosp, Sch Med, Dept Pediat, Seattle, WA 98195 USA. RP Su, HC (reprint author), Bldg 10CRC,Room 5W3940,10CRC Ctr Dr,MSC 1456, Bethesda, MD 20892 USA. EM hsu@niaid.nih.gov RI Su, Helen/H-9541-2015; OI Su, Helen/0000-0002-5582-9110; Zhang, Qian/0000-0002-9040-3289 FU National Institutes of Health, the National Institute of Allergy and Infectious Diseases; Lazarus Family Scholarship through the George Washington University School of Medicine and Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health, the National Institute of Allergy and Infectious Diseases. J.C.D also received support from the Lazarus Family Scholarship through the George Washington University School of Medicine and Health Sciences. We thank Huie Jing for sharing unpublished data; Yu Zhang for helpful discussions; and Andrew Snow, Dara Strauss-Albee, and Bernice Lo for reading this manuscript. NR 88 TC 40 Z9 42 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2010 VL 29 IS 3-4 BP 131 EP 139 DI 10.3233/DMA-2010-0737 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 696RF UT WOS:000285458400003 PM 21178272 ER PT J AU Shearin, AL Ostrander, EA AF Shearin, Abigail L. Ostrander, Elaine A. TI Leading the way: canine models of genomics and disease SO DISEASE MODELS & MECHANISMS LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; ROD-CONE DEGENERATION; GERMAN-SHEPHERD DOG; HOGG-DUBE-SYNDROME; URINARY-BLADDER; LINKAGE ANALYSIS; RENAL CYSTADENOCARCINOMA; RETINITIS-PIGMENTOSA; WIDE ASSOCIATION; DOMESTIC DOG AB In recent years Canis familiaris, the domestic dog, has drawn considerable attention as a system in which to investigate the genetics of disease susceptibility, morphology and behavior. Because dogs show remarkable intrabreed homogeneity, coupled with striking interbreed heterogeneity, the dog offers unique opportunities to understand the genetic underpinnings of natural variation in mammals, a portion of which is disease susceptibility. In this review, we highlight the unique features of the dog, such as population diversity and breed structure, that make it particularly amenable to genetic studies. We highlight recent advances in understanding the architecture of the dog genome, which propel the system to the forefront of consideration when selecting a system for disease gene studies. The most notable benefit of using the dog for genetic studies is that dogs get many of the same diseases as humans, with a similar frequency, and the same genetic factors are often involved. We discuss two approaches for localizing disease genes in the dog and provide examples of ongoing studies. C1 [Shearin, Abigail L.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. OI Ostrander, Elaine/0000-0001-6075-9738 FU American Kennel Club Canine Health Foundation; National Human Genome Research Institute FX We thank the dog owners who have contributed DNA samples for our studies for their time and generosity We gratefully acknowledge the American Kennel Club Canine Health Foundation and the Intramural program of the National Human Genome Research Institute for their support Deposited in PMC for release after 12 months NR 88 TC 67 Z9 67 U1 3 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JAN-FEB PY 2010 VL 3 IS 1-2 BP 27 EP 34 DI 10.1242/dmm.004358 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 562BI UT WOS:000275023400007 PM 20075379 ER PT J AU Parker, RK Dawsey, SM Abnet, CC White, RE AF Parker, R. K. Dawsey, S. M. Abnet, C. C. White, R. E. TI Frequent occurrence of esophageal cancer in young people in western Kenya SO DISEASES OF THE ESOPHAGUS LA English DT Article DE age of onset; esophageal cancer; ethnicity; Kenya ID SUB-SAHARAN AFRICA AB P>Esophageal cancer has a strikingly uneven geographical distribution, resulting in focal endemic areas in several countries. One such endemic area is in western Kenya. We conducted a retrospective review of all pathology-confirmed malignancies diagnosed at Tenwek Hospital, Bomet District, between January 1999 and September 2007. Tumor site, histology, sex, age, ethnicity, and location of residence were recorded. Cases were analyzed within and outside a traditional catchment area defined as < 50 km from the hospital. Since 1999, the five most common cancer sites were the esophagus, stomach, prostate, colorectum, and cervix. Esophageal cancer accounted for 914 (34.6%) of the 2643 newly diagnosed cancers and showed increasing trends within and outside the catchment area. Fifty-eight (6.3%) patients were < 30 years old and 9 (1%) were < 20 years old; the youngest patient was 14 years at diagnosis. Young cases (< 30) were more common among patients of Kalenjin ethnicity (9.2%) than among other ethnicities (1.7%) (odds ratio [95% confidence interval] 5.7 [2.1-15.1]). This area of western Kenya is a high-risk region for esophageal cancer and appears unique in its large proportion of young patients. Our findings support the need for further study of both environmental and genetic risk factors for esophageal cancer in this area. C1 [Parker, R. K.; White, R. E.] Tenwek Hosp, Bomet 20400, Kenya. [Parker, R. K.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Dawsey, S. M.; Abnet, C. C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [White, R. E.] Brown Univ, Rhode Isl Hosp, Dept Surg, Brown Med Sch, Providence, RI 02903 USA. RP White, RE (reprint author), Tenwek Hosp, POB 39, Bomet 20400, Kenya. EM russ.white@wgm.org RI Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU Division of Cancer Epidemiology and Genetics; National Cancer Institute FX This study was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute. NR 19 TC 20 Z9 20 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PY 2010 VL 23 IS 2 BP 128 EP 135 DI 10.1111/j.1442-2050.2009.00977.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 556VT UT WOS:000274622100008 PM 19473205 ER PT B AU Peluso, M Srivatanakul, P Munnia, A Ceppi, M Jedpiyawongse, A Sangrajrang, S Piro, S Boffetta, P AF Peluso, M. Srivatanakul, P. Munnia, A. Ceppi, M. Jedpiyawongse, A. Sangrajrang, S. Piro, S. Boffetta, P. BE Alvarez, E Cunha, R TI Diet, Life-Style Habits and Malondialdehyde-Deoxyguanosine Adducts in a Group of Subjects Resident in the Rayong Province, Thailand SO DNA ADDUCTS: FORMATION, DETECTION AND MUTAGENESIS SE DNA Properties and Modifications Functions and Interactions Recombination and Applications LA English DT Article; Book Chapter ID OXIDATIVE DNA-DAMAGE; LUNG-CANCER; BLADDER-CANCER; LIPID-PEROXIDATION; FREE-RADICALS; FATTY-ACID; RISK; POLYMORPHISM; ASSOCIATION; SMOKING AB Most human cancers result from environmental exposures and gene-environment interactions. Diet is an important component of lifestyle and its role in the maintenance of good health and as a determinant of different kind of chronic diseases, including cancer, has been extensively analyzed. Diet can contribute to cancer risk through the consumption of food mutagens, including those generated by cooking. On the other hand, diet that emphasizes the consumption of whole grain foods, legumes, vegetables and fresh fruit and that limit animal fat has been associated with decreased cancer risk. Indeed, a general protective effect against cancers at different sites has been reported for a number of fresh fruit and vegetables. In particular, fresh fruit is a food rich of phytochemicals that can act against reactive oxygen species (ROS) formation and induce the expression of DNA repair systems. Among life-style habits, tobacco cigarette smoking is an established cancer risk factor. In addition to be a relevant source of mutagens, tobacco smoke is also a major source of oxidative stress and ROS, capable to cause oxidative DNA damage. ROS can also induce lipid peroxidation (LPO), whose by-products can lead to endogenous DNA damage formation. MDA is a natural product of LPO, also formed during prostaglandins (PGH(2)) biosynthesis via cyclooxygenase (COX-1 and COX-2). MDA is an aldehyde capable to interact with cellular constituents including DNA, inducing the formation of M(1)dG adducts. The reaction with deoxyguanosine (dG) origins the formation of 3-(2-deoxy-beta-D-erythro-pentafuranosyppyrimido[1,2-alpha]purin-10(3H)-one, e.g. the M(1)dG adducts. In addition to LPO and PGH2 biosynthesis, the formation of M(1)dG adducts can be induced by ROS through the production of base propenal intermediates. M(1)dG adducts have been shown to block the replication of DNA and induce base pair and frameshift mutations. Moreover, increased levels of M(1)dG adducts have been found in number of cancer patients. Higher amount of M(1)dG adducts have been also associated to worst surviving in lung cancer patients. Thus, the analysis of M(1)dG adduct formation is considered a promising biomarker that can reflect the whole oxidant status of an organism. In the present study, we have investigated the relationship between tobacco smoking, the consumption of fresh fruit and the formation of M(1)dG adducts in a group of people resident in Map Ta Phut (MTP), Rayong province, Thailand, including 53 residents in the Map Ta Phut Industrial Estate (MIE) area, and 46 individuals living in a control district of the same province without industrial exposures. The DNA adduct analysis was performed using the (32)P-DNA postlabelling assay (Munnia et al., 2006). The potential involvement of the polymorphism of glutathione S-transferase Mu-1 (GSTM1) in the formation of endogenous DNA adducts has been also evaluated. Our findings indicate a statistically significant effect of tobacco smoke on M(1)dG formation (p < 0.05). The increased intake of fresh fruit was inversely associated to the M(1)dG adduct production (p < 0.05). Then, the GSTM1 polymorphism was not associated with the formation of M(1)dG adducts. Our data indicate that tobacco smoking habits can induce an enhanced formation of M(1)dG adducts, possibly through the production of ROS and LPO. Conversely, the consumption of fresh fruits was associated to a decreased formation of DNA damage. The increased formation of M(1)dG adducts in current smokers can be related to an excess of LPO induced from tobacco smoke constituents, as well from ROS produced during carcinogen metabolism. The protective effects of fresh fruit on M(1)dG adduct production may act on different biological mechanisms, for example by the induction of enzymes involved in DNA repair and by antioxidant effects. The GSTM1 polymorphism could be not relevant for the frequency of M(1)dG adducts. C1 [Peluso, M.] ISPO Canc Prevent & Res Inst, Canc Risk Factor Branch, I-50139 Florence, Italy. [Srivatanakul, P.; Jedpiyawongse, A.; Sangrajrang, S.] Natl Canc Inst, Bangkok 10400, Thailand. [Ceppi, M.] Natl Canc Inst, I-16123 Genoa, Italy. [Boffetta, P.] Int Agcy Res Canc, F-69372 Lyon 08, France. RP Peluso, M (reprint author), ISPO Canc Prevent & Res Inst, Canc Risk Factor Branch, Via Cosimo Vecchio 2, I-50139 Florence, Italy. EM m.peluso@ispo.toscana.it OI PIRO, SARA/0000-0003-4198-7035 NR 59 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 978-1-60741-433-9 J9 DNA PROP MODIF FUNCT PY 2010 BP 83 EP 101 PG 19 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA BOC39 UT WOS:000276166200004 ER PT S AU Chen, SY Misra, D Thoma, GR AF Chen, Siyuan Misra, Dharitri Thoma, George R. BE Likforman-Sulem, L Agam, G TI Efficient Automatic OCR Word Validation Using Word Partial Format Derivation and Language Model SO DOCUMENT RECOGNITION AND RETRIEVAL XVII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XVII CY JAN 19-21, 2010 CL San Jose, CA SP SPIE, IS & T (Soc Imaging Sci & Technol), Inst Telecom AB In this paper we present an OCR validation module, implemented for the System for Preservation of Electronic Resources (SPER) developed at the U.S. National Library of Medicine. 1 The module detects and corrects suspicious words in the OCR output of scanned textual documents through a procedure of deriving partial formats for each suspicious word, retrieving candidate words by partial-match search from lexicons, and comparing the joint probabilities of N-gram and OCR edit transformation corresponding to the candidates. The partial format derivation, based on OCR error analysis, efficiently and accurately generates candidate words from lexicons represented by ternary search trees. In our test case comprising a historic medico-legal document collection, this OCR validation module yielded the correct words with 87% accuracy and reduced the overall OCR word errors by around 60%. C1 [Chen, Siyuan; Misra, Dharitri; Thoma, George R.] US Natl Lib Med, Bethesda, MD 20894 USA. RP Chen, SY (reprint author), US Natl Lib Med, Bethesda, MD 20894 USA. 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 978-0-8194-7927-3 J9 PROC SPIE PY 2010 VL 7534 AR 75340O DI 10.1117/12.838853 PG 8 WC Computer Science, Information Systems; Optics; Imaging Science & Photographic Technology SC Computer Science; Optics; Imaging Science & Photographic Technology GA BRR44 UT WOS:000283495700024 ER PT S AU Kim, J Le, DX Thoma, GR AF Kim, Jongwoo Le, Daniel X. Thoma, George R. BE Likforman-Sulem, L Agam, G TI Naive Bayes and SVM classifiers for classifying Databank Accession Number sentences from online biomedical articles SO DOCUMENT RECOGNITION AND RETRIEVAL XVII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XVII CY JAN 19-21, 2010 CL San Jose, CA SP SPIE, IS & T (Soc Imaging Sci & Technol), Inst Telecom DE Naive Bayes; Support Vector Machine (SVM); databank; labeling; text classification; bibliographic information AB This paper describes two classifiers, Nave Bayes and Support Vector Machine (SVM), to classify sentences containing Databank Accession Numbers, a key piece of bibliographic information, from online biomedical articles. The correct identification of these sentences is necessary for the subsequent extraction of these numbers. The classifiers use words that occur most frequently in sentences as features for the classification. Twelve sets of word features are collected to train and test the classifiers. Each set has a different number of word features ranging from 100 to 1,200. The performance of each classifier is evaluated using four measures: Precision, Recall, F-Measure, and Accuracy. The Naive Bayes classifier shows performance above 93.91% at 200 word features for all four measures. The SVM shows 98.80% Precision at 200 word features, 94.90% Recall at 500 and 700, 96.46% F-Measure at 200, and 99.14% Accuracy at 200 and 400. To improve classification performance, we propose two merging operators, Max and Harmonic Mean, to combine results of the two classifiers. The final results show a measureable improvement in Recall, F-Measure, and Accuracy rates. C1 [Kim, Jongwoo; Le, Daniel X.; Thoma, George R.] Natl Lib Med, Bethesda, MD 20894 USA. RP Kim, J (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM jongkim@mail.nih.gov NR 13 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 978-0-8194-7927-3 J9 PROC SPIE PY 2010 VL 7534 AR 75340U DI 10.1117/12.838961 PG 8 WC Computer Science, Information Systems; Optics; Imaging Science & Photographic Technology SC Computer Science; Optics; Imaging Science & Photographic Technology GA BRR44 UT WOS:000283495700030 ER PT S AU Zhang, XL Zou, J Le, DX Thoma, G AF Zhang, Xiaoli Zou, Jie Le, Daniel X. Thoma, George BE Likforman-Sulem, L Agam, G TI A stacked sequential learning method for investigator name recognition from Web-based medical articles SO DOCUMENT RECOGNITION AND RETRIEVAL XVII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Document Recognition and Retrieval XVII CY JAN 19-21, 2010 CL San Jose, CA SP SPIE, IS & T (Soc Imaging Sci & Technol), Inst Telecom DE Stacked Sequential Learning; Support Vector Machine (SVM); Named Entity Recognition AB "Investigator Names" is a newly required field in MEDLINE citations. It consists of personal names listed as members of corporate organizations in an article. Extracting investigator names automatically is necessary because of the increasing volume of articles reporting collaborative biomedical research in which a large number of investigators participate. In this paper, we present an SVM-based stacked sequential learning method in a novel application recognizing named entities such as the first and last names of investigators from online medical journal articles. Stacked sequential learning is a meta-learning algorithm which can boost any base learner. It exploits contextual information by adding the predicted labels of the surrounding tokens as features. We apply this method to tag words in text paragraphs containing investigator names, and demonstrate that stacked sequential learning improves the performance of a nonsequential base learner such as an SVM classifier. C1 [Zhang, Xiaoli; Zou, Jie; Le, Daniel X.; Thoma, George] NIH, Commun Engn Branch, Natl Lib Med, Bethesda, MD 20814 USA. RP Zhang, XL (reprint author), NIH, Commun Engn Branch, Natl Lib Med, Bethesda, MD 20814 USA. EM zhangxiaol@mail.nih.gov; jzou@mail.nih.gov; danle@mail.nih.gov; gthoma@mail.nih.gov NR 13 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 978-0-8194-7927-3 J9 PROC SPIE PY 2010 VL 7534 AR 753404 DI 10.1117/12.839141 PG 7 WC Computer Science, Information Systems; Optics; Imaging Science & Photographic Technology SC Computer Science; Optics; Imaging Science & Photographic Technology GA BRR44 UT WOS:000283495700004 ER PT S AU Hazelwood, LA Free, RB Sibley, DR AF Hazelwood, Lisa A. Free, R. Benjamin Sibley, David R. BE Neve, KA TI Dopamine Receptor-Interacting Proteins SO DOPAMINE RECEPTORS, SECOND EDITION SE Receptors Series LA English DT Article; Book Chapter DE Interacting proteins; Signalplex; Yeast two-hybrid; Immunoprecipitation; Proteomics ID MEDIATED ERK ACTIVATION; ACID-BINDING-PROTEIN; PDZ DOMAIN PROTEIN; COUPLED-RECEPTOR; D1 RECEPTOR; CELL-SURFACE; D2 RECEPTOR; QUALITY-CONTROL; NEOSTRIATAL NEURONS; POTASSIUM CHANNELS AB Historically, dopamine receptors (DARs) and other G protein-coupled receptors (GPCRs) were believed to be independent signaling units in the plasma membrane, interacting only transiently with G proteins to initiate a downstream signaling cascade. However, in recent years it has become clear that DARs do not function in isolation, but in fact exist as members of macromolecular protein complexes. The DAR protein complex, or the signalplex, consists of a variety of protein interactors that may be transient or stable in nature and that are collectively referred to as dopamine receptor-interacting proteins (DRIPs). Ultimately, the goal of the signalplex is to organize the cellular machinery or signaling components that are critical to the DAR at any given time in an orderly fashion. This higher level of organization around the DAR enables the receptor to process all information, from extracellular ligands or intracellular signaling molecules, and propagate the necessary cellular response in a timely and efficient manner. C1 [Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Rockville, MD 20852 USA. [Free, R. Benjamin] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20852 USA. [Hazelwood, Lisa A.] NINDS, Sect Mol Neuropharmacol, NIH, Bethesda, MD 20852 USA. RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA. EM sibley@helix.nih.gov NR 106 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1048-6909 BN 978-1-60327-332-9 J9 RECEPT SER JI Recept. Ser. PY 2010 BP 219 EP 254 DI 10.1007/978-1-60327-333-6_9 D2 10.1007/978-1-60327-333-6 PG 36 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOK38 UT WOS:000276890800009 ER PT S AU Fuxe, K Marcellino, D Guidolin, D Woods, A Agnati, L AF Fuxe, Kjell Marcellino, Daniel Guidolin, Diego Woods, Amina Agnati, Luigi BE Neve, KA TI Dopamine Receptor Oligomerization SO DOPAMINE RECEPTORS, SECOND EDITION SE Receptors Series LA English DT Article; Book Chapter DE Dopamine receptor subtypes; Receptor receptor interactions Dopamine homomers; Dopamine heteromers; Receptor mosaic; Cooperativity; G protein-coupled receptors; Ion channel receptors; Receptor tyrosine kinase ID ADENOSINE A(2A) RECEPTORS; PROTEIN-COUPLED RECEPTORS; CAMP-REGULATED PHOSPHOPROTEIN; RAT STRIATAL MEMBRANES; CENTRAL NERVOUS-SYSTEM; MESSENGER-RNA LEVELS; NUCLEUS-ACCUMBENS; BASAL GANGLIA; HETEROMERIC COMPLEXES; BINDING-SITES AB Each dopamine (DA) receptor subtype physically interacts with its own kind (homomers) or other receptors (heteromers) in the plasma membrane of neurons in the basal ganglia to form dimeric or high-order receptor oligomers, termed dimeric or high-order receptor mosaics (RMs). Two types of heteromeric DA RMs are primarily discussed, namely type 1 receptor mosaic (RM1) formed by different DA receptor (DA-R) subtypes that display classical cooperativity and type 2 receptor mosaic (RM2) formed by DA-R subtypes physically interacting with other receptors that display non-classical cooperativity. The D-2 receptor can form a RM1 with either D-1 or D-3 receptor subtypes as well as different types of RM2 with A(2A), mGluR5, CB1, neuropeptide receptors (SSR5, NTS1, CCK-2), and N-methyl-D-aspartate (NMDA) receptors. Trimeric A(2A)-D-2-mGluR5 and A(2A)-D-2-CB1 RM2 may exist in striatal neuronal networks and are also discussed. Di receptors can form RM1 with D-3 receptors and different types of RM2 with A(1), mu-opioid, and NMDA receptors. D-3 receptors can form a RM2 with A2(A) receptors and D-5 receptors can form a RM2 with gamma-aminobutyric acid (GABA)-A receptors. Through existing as part of a horizontal molecular network, RMs fine-tune multiple effector systems already at the level of the membrane, involving Ca2+, Na+, and K+ and including G protein-regulated inwardly rectifying potassium channels (GIRK), adenylyl cyclase (AC), phospholipase C (PLC), and dopamine transporter activity. The synaptic strength is particularly modulated by DA receptors within DA receptor RM2 that involve ligand-gated ion channels such as GABA-A and NMDA receptors. The existence of a RM2 formed by D-2 receptors and receptor tyrosine kinase (RTK) receptors is also likely to exist and bears high relevance for the integration of trophic and informational signals within striatal networks. A novel neuropsychopharmacology may develop on the basis of DA receptor-containing RMs in the brain from the unique pharmacological properties afforded by their receptor receptor interactions. C1 [Fuxe, Kjell; Marcellino, Daniel] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. [Guidolin, Diego] Univ Padua, Sect Anat, Dept Human Anat & Physiol, I-35121 Padua, Italy. [Woods, Amina] NIDA, Intramural Res Program, US Dept HHS, NIH, Baltimore, MD 21224 USA. [Agnati, Luigi] Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41100 Modena, Italy. RP Fuxe, K (reprint author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. EM kjell.fuxe@ki.se NR 154 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 1048-6909 BN 978-1-60327-332-9 J9 RECEPT SER JI Recept. Ser. PY 2010 BP 255 EP 280 DI 10.1007/978-1-60327-333-6_10 D2 10.1007/978-1-60327-333-6 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BOK38 UT WOS:000276890800010 ER PT S AU Geijer, C Joseph-Strauss, D Simchen, G Barkai, N Hohmann, S AF Geijer, Cecilia Joseph-Strauss, Daphna Simchen, Giora Barkai, Naama Hohmann, Stefan BE Lubzens, E Cerda, J Clark, M TI Saccharomyces cerevisiae Spore Germination SO DORMANCY AND RESISTANCE IN HARSH ENVIRONMENTS SE Topics in Current Genetics LA English DT Article; Book Chapter ID NUCLEAR MAGNETIC-RESONANCE; CELL-CYCLE; TREHALOSE MOBILIZATION; YEAST SPORULATION; GENE-EXPRESSION; ASCOSPORES; MICROSCOPY; ELECTRON; PATHWAY; RAS AB Saccharomyces cerevisiae spore germination is the process in which dormant spores resume growth. Upon exposure to glucose and other essential nutrients, the spore gradually loses its spore characteristics and starts acquiring properties of a vegetative cell. Translation and transcription are initiated early in the germination process. Global gene expression analysis has revealed that germination can be divided into two stages prior to the first cell cycle. During the first stage, the transcriptional programme resembles the general response of yeast cells to glucose. During the second stage, the spores sense and respond also to other nutrients than glucose. In addition, genes involved in conjugation are upregulated in germinating spores and mating is initiated before the first mitotic cell cycle. Here, we review the current understanding of the cellular rearrangements and the genes and proteins involved in germination. C1 [Geijer, Cecilia; Hohmann, Stefan] Univ Gothenburg, Dept Cell & Mol Biol Microbiol, S-40530 Gothenburg, Sweden. [Joseph-Strauss, Daphna] NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Simchen, Giora] Hebrew Univ Jerusalem, Dept Genet, IL-91904 Jerusalem, Israel. [Barkai, Naama] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. [Barkai, Naama] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. RP Hohmann, S (reprint author), Univ Gothenburg, Dept Cell & Mol Biol Microbiol, Box 462, S-40530 Gothenburg, Sweden. EM stefan.hohmann@gu.se RI Hohmann, Stefan/K-9895-2013 OI Hohmann, Stefan/0000-0002-0809-1985 NR 33 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1610-2096 BN 978-3-642-12421-1 J9 TOP CURR GENET JI Top. Curr. Genet. PY 2010 VL 21 BP 29 EP 41 DI 10.1007/978-3-642-12422-8_3 D2 10.1007/978-3-642-12422-8 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BQM93 UT WOS:000281350300003 ER PT B AU Price, DK Hsing, AW AF Price, Douglas K. Hsing, Ann W. BE Figg, WD Chau, CH Small, EJ TI Androgens and Prostate Cancer SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Prostate cancer; Androgens; Testosterone; Replacement therapy ID TESTOSTERONE-REPLACEMENT THERAPY; LOW SERUM TESTOSTERONE; RANDOMIZED CONTROLLED-TRIAL; ENDOGENOUS SEX-HORMONES; HYPOGONADAL MEN; RADICAL PROSTATECTOMY; STEROID-HORMONES; AFRICAN-AMERICAN; UNITED-STATES; RISK LOCUS AB Prostate cancer is the most common nonskin cancer among American men and the third leading cause of cancer deaths. Research data over many years of study support the role of androgen in driving prostate cancer growth, proliferation, and progression. Androgens are steroid hormones that induce the differentiation and maturation of the male reproductive organs. Testosterone is the principal androgen in circulation, while dihydrotestosterone (DHT) is the primary nuclear androgen, and the action of DHT in the prostate is mediated by the androgen receptor. Within the prostate. DHT binds to the androgen receptor to form an intracellular complex that binds to androgen-response elements in the DNA of prostate cells inducing proliferation. Testosterone deficiency is common among aging American males, and a number of men suffering from testosterone deficiency may be relieved of their symptoms, receiving a boost in their quality of life, but are often denied treatment due to the fear that the addition of higher testosterone from replacement therapy may cause growth of occult prostate cancer. Several small studies show that, with the right patient population, testosterone replacement after curative therapy is safe. However, a large placebo-controlled prospective trial to provide the definitive study is needed. C1 [Price, Douglas K.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Price, DK (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. EM dkprice@mai.nih.gov NR 50 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 53 EP 59 DI 10.1007/978-1-60327-829-4_4 D2 10.1007/978-1-60327-829-4 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600004 ER PT B AU Sissung, TM Figg, WD AF Sissung, Tristan M. Figg, William D. BE Figg, WD Chau, CH Small, EJ TI Clinical Pharmacology and Pharmacogenetics of Chemotherapy in Prostate Cancer SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Docetaxel; Mitoxantrone; Estramustine; Satraplatin; Prostate cancer; Pharmacogenetics; Pharmacology ID SINGLE-NUCLEOTIDE POLYMORPHISMS; CELL LUNG-CANCER; TANDEM MASS-SPECTROMETRY; MITOXANTRONE PLUS PREDNISONE; RESISTANCE PROTEIN-1 MRP1; PLATINUM DRUG-RESISTANCE; PREGNANE-X-RECEPTOR; PHASE-II TRIAL; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN AB Cytotoxic chemotherapy using docetaxel, estramustine, and mitoxantrone is often employed to treat men with hormone-refractory prostate tumors. More recently, oral satraplatin has been studied as an alternative to docetaxel-based therapies. These cytotoxic agents have diverse mechanisms of action and disposition. Moreover, there is often wide inter-individual variation in the pharmacokinetics, toxicity, and clinical outcome following administration of these agents in patients with prostate cancer. This chapter summarizes what is known about the basic clinical pharmacology of these agents and discusses the mechanisms and implications of inter-individual variation in treatment. C1 [Sissung, Tristan M.; Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov; wdfigg@helix.nih.gov NR 151 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 163 EP 177 DI 10.1007/978-1-60327-829-4_15 D2 10.1007/978-1-60327-829-4 PG 15 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600015 ER PT B AU Fojo, AT Adelberg, DE AF Fojo, Antonio Tito Adelberg, David E. BE Figg, WD Chau, CH Small, EJ TI Microtubule Targeting Agents SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Cytoskeleton; Microtubule; Tubulin; Chemotherapy; Prostate cancer ID ADVANCED SOLID TUMORS; REFRACTORY PROSTATE-CANCER; ANALOG IXABEPILONE BMS-247550; TUBULIN COLCHICINE COMPLEXES; PACLITAXEL-RESISTANT CELLS; TAXOL-BINDING-SITE; ALPHA-BETA-TUBULIN; PHASE-II TRIAL; EVERY 3 WEEKS; STABILIZING AGENTS AB Microtubules are intracellular filamentous structures that comprise the cytoskeleton of all eukaryotic cells. They play a critical role in various cellular processes such as mitosis and have become an essential target for the chemotherapeutic approach to a wide spectrum of malignancies. It is thus crucial to understand the basic biology of the microtubule and be familiar with the various microtubule targeting agents used clinically. This chapter provides an overview of microtubule physiology and the novel microtubule-targeting chemotherapeutic agents that are currently being evaluated for the treatment of taxane-refractory, castration-resistant prostate cancer. C1 [Fojo, Antonio Tito] NCI, Expt Therapeut Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Fojo, AT (reprint author), NCI, Expt Therapeut Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM fojot@mail.nih.gov NR 117 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 179 EP 194 DI 10.1007/978-1-60327-829-4_16 D2 10.1007/978-1-60327-829-4 PG 16 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600016 ER PT B AU Chau, CH Figg, WD AF Chau, Cindy H. Figg, William D. BE Figg, WD Chau, CH Small, EJ TI Principles of Antiangiogenic Therapy SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Angiogenesis; Angiogenic switch; Angiogenesis inhibitor; Microvessel density; Antiangiogenic therapy ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; TUMOR-ASSOCIATED MACROPHAGES; PROSTATE-CANCER CELLS; FACTOR EXPRESSION; METRONOMIC CHEMOTHERAPY; MICROVESSEL DENSITY; ENDOGENOUS INHIBITORS; ANGIOGENIC SWITCH; FACTOR 1-ALPHA AB Angiogenesis is a critical process to both tumor growth and metastasis in prostate cancer. The markers of angiogenesis in prostate cancer have been identified and could potentially provide prognostic information in addition to clinicopathological data and patient outcome. Promising preclinical studies have led to the initiation of phase I/II studies of antiangiogenic therapy in combination with docetaxel-based chemotherapy in patients with castration-resistant prostate cancer. This chapter describes the mechanisms of the angiogenic process, establishes its role in prostate cancer, and discusses the markers of angiogenesis in prostate cancer, in an attempt to provide an overall understanding of the basic principles of antiangiogenic therapy. C1 [Chau, Cindy H.; Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chau, CH (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM chauc@mail.nih.gov; chauc@mail.nih.gov NR 84 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 197 EP 205 DI 10.1007/978-1-60327-829-4_17 D2 10.1007/978-1-60327-829-4 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600017 ER PT B AU Gardner, ER Di Lorenzo, G Figg, WD AF Gardner, Erin R. Di Lorenzo, Giuseppe Figg, William D. BE Figg, WD Chau, CH Small, EJ TI Thalidomide and Analogs SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Thalidomide; Lenalidomide; Angiogenesis; Prostate cancer; Immunomodulatory ID INDEPENDENT PROSTATE-CANCER; PHASE-II TRIAL; MITOXANTRONE PLUS PREDNISONE; DOCETAXEL; DEXAMETHASONE; ANGIOGENESIS; ESTRAMUSTINE; CARCINOMA; CYCLOPHOSPHAMIDE; LENALIDOMIDE AB Thalidomide (Thalomid (R)), originally marketed as a sedative in Europe in the 1950s but withdrawn after teratogenicity was observed, has experienced a resurgence of interest due to its apparent anti-angiogenic and immunomodulatory properties. Thalidomide is currently in clinical testing for the treatment of prostate cancer. Numerous studies that have been completed, or are currently ongoing, have demonstrated promising activity. Thalidomide has been tested as a single agent and in combination with both targeted agents, such as bevacizumab, and traditional cytotoxic drugs, such as paclitaxel and docetaxel, in the majority of the studies. A range of thalidomide analogs have been generated in an effort to improve the clinical activity while reducing the side effect profile. Lenalidomide (Revlimid (TM)), an immunomodulatory analog of thalidomide, has entered clinical trials in prostate cancer and is being tested in many of the same combinations. This chapter reviews the clinical trials of thalidomide and lenalidomide initiated or completed to date, including dosing, clinical response, and toxicity. C1 [Figg, William D.] NCI, Med Oncol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI, SAIC Frederick Inc, Clin Pharmacol Program, Frederick, MD 21701 USA. [Di Lorenzo, Giuseppe] AOU Federico II, Med Oncol, Naples, Italy. RP Figg, WD (reprint author), NCI, Med Oncol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov; wdfigg@helix.nih.gov NR 48 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 215 EP 223 DI 10.1007/978-1-60327-829-4_19 D2 10.1007/978-1-60327-829-4 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600019 ER PT B AU Aragon-Ching, JB Dahut, W AF Aragon-Ching, Jeanny B. Dahut, William BE Figg, WD Chau, CH Small, EJ TI Investigational Angiogenesis Inhibitors SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Antiangiogenesis; Clinical trials; Prostate cancer; Tyrosine kinases ID ENDOTHELIAL GROWTH-FACTOR; HUMAN PROSTATE-CANCER; PHASE-II TRIAL; MEMBRANE-TYPE-1 MATRIX-METALLOPROTEINASE; METASTATIC COLORECTAL-CANCER; INDUCIBLE FACTOR 1-ALPHA; IN-VITRO EXPRESSION; CELL LUNG-CANCER; TUMOR ANGIOGENESIS; MICROVESSEL DENSITY AB Targeting angiogenesis is an evolving field of cancer research. Tumor angiogenesis is considered as an important step in the progression and metastasis of prostate cancer. Several pathways that converge toward promotion of growth, proliferation, and survival of prostate cancer cells have been targeted, including modulation of proangiogenic factors such as vascular endothelial growth factor (VEGF), tyrosine kinases, cytokines, and the extracellular matrix. Accurately measuring antitumor activity remains a challenge with the use of investigational angiogenesis inhibitors in prostate cancer. C1 [Aragon-Ching, Jeanny B.] George Washington Univ, Dept Med, Washington, DC 20052 USA. [Dahut, William] NCI, Med Oncol Branch, CCR, NIH,Clin Ctr, Bethesda, MD 20892 USA. RP Aragon-Ching, JB (reprint author), George Washington Univ, Dept Med, Washington, DC 20052 USA. EM jaragonching@mfa.gwu.edu OI Aragon-Ching, Jeanny/0000-0002-6714-141X NR 95 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 225 EP 232 DI 10.1007/978-1-60327-829-4_20 D2 10.1007/978-1-60327-829-4 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600020 ER PT B AU Madan, RA Gulley, JL Celestin, J Arlen, PM Schlom, J AF Madan, Ravi A. Gulley, James L. Celestin, Jackie Arlen, Philip M. Schlom, Jeffrey BE Figg, WD Chau, CH Small, EJ TI Cancer Immunology, Immunotherapeutics, and Vaccine Approaches SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Prostate cancer; Cancer vaccines; Immunotherapy ID COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; REFRACTORY PROSTATE-CANCER; ANTIGEN-PRESENTING CELLS; ANDROGEN-DEPRIVATION THERAPY; ALLOGENEIC CELLULAR IMMUNOTHERAPY; DRAINING LYMPH-NODES; PHASE-I TRIAL; COSTIMULATORY MOLECULES; COMBINATION THERAPY AB Although most patients can be cured of their prostate cancer by initial definitive therapy, up to 40% of patients may have recurrent disease. For these patients, hormonal manipulations may provide initial benefit and chemotherapy has been demonstrated to extend survival when the disease is castration-resistant and metastatic. In spite of these therapeutic approaches, additional therapies are needed. Therapeutic cancer vaccines have been developed using several platforms to enhance immune targeting of prostate cancer cells and have shown promise in early clinical trials. There are several therapeutic cancer vaccine platforms for prostate cancer including vector-based, antigen-presenting cell pulsed and whole tumor-cell vaccines. Several phase II vaccine trials have demonstrated some degree of clinical benefit. Some of these trials, however, have underscored the need for new paradigms to be developed to evaluate the clinical benefit and utility of cancer vaccines. In addition, vaccines have demonstrated compatibility and synergy with standard therapies in both preclinical and clinical models. Several phase III trials with immunotherapies in prostate cancer are in late stages of planning or are ongoing. Future immunotherapy trials should focus on identifying appropriate patient populations most likely to benefit from vaccine therapy and appropriate trial endpoints. C1 [Madan, Ravi A.; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Med Oncol Branch, Bethesda, MD 20892 USA. [Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Celestin, Jackie] Univ Connecticut, Farmington, CT USA. [Arlen, Philip M.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, Med Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 126 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 305 EP 319 DI 10.1007/978-1-60327-829-4_27 D2 10.1007/978-1-60327-829-4 PG 15 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600027 ER PT B AU Parnes, HL House, MG Tangrea, JA AF Parnes, Howard L. House, Margaret G. Tangrea, Joseph A. BE Figg, WD Chau, CH Small, EJ TI Prostate Cancer Chemoprevention Strategies SO DRUG MANAGEMENT OF PROSTATE CANCER LA English DT Article; Book Chapter DE Chemoprevention; Agent development; Study endpoints; Patient cohorts; PCPT; SELECT; REDUCE ID RANDOMIZED CONTROLLED-TRIAL; PREVENTION TRIAL; VITAMIN-E; INTRAEPITHELIAL NEOPLASIA; FOLLOW-UP; 5-ALPHA-REDUCTASE ISOENZYMES; COLORECTAL-CANCER; SERUM-LEVELS; RISK; SELENIUM AB Carcinogenesis is the multistep process by which normal cells undergo malignant transformation. The clinical expression of cancer may be prevented or delayed either by risk factor modification, such as quitting smoking, or by the administration of drugs to prevent or delay the clinical expression of the malignant phenotype. This chapter focuses on the latter approach, often referred to as "chemoprevention." Specifically, it addresses the two key issues distinguishing cancer prevention from cancer treatment agent development: selection of study endpoints and patient cohorts. In addition, a comprehensive update is provided of recently completed and ongoing phase 1, 2, and 3 prostate cancer prevention clinical trials conducted under the auspices of the Division of Cancer Prevention, NCI. C1 [Parnes, Howard L.] NCI, Prostate & Urol Canc Res Grp, Canc Prevent Div, Ctr Canc Res, Bethesda, MD 20892 USA. [House, Margaret G.] NCI, Canc Prevent Div, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Parnes, HL (reprint author), NCI, Prostate & Urol Canc Res Grp, Canc Prevent Div, Ctr Canc Res, Bethesda, MD 20892 USA. EM parnesh@mail.nih.gov NR 65 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-60327-831-7 PY 2010 BP 351 EP 362 DI 10.1007/978-1-60327-829-4_31 D2 10.1007/978-1-60327-829-4 PG 12 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BRE85 UT WOS:000282532600031 ER PT B AU Manning, TJ Abadi, G Bishop, K McLeod, K Bullock, G Kean, G Grant, D Anderson, S Cooper-White, K Sermons, S Patel, O Phillips, D Potter, T Nienow, J Klausmeyer, P Newman, D AF Manning, Thomas J. Abadi, Giso Bishop, Karly McLeod, Kristen Bullock, Gunter Kean, Greg Grant, Devin Anderson, Stuart Cooper-White, Katrice Sermons, Shanda Patel, Om Phillips, Dennis Potter, Thomas Nienow, James Klausmeyer, Paul Newman, David BA Govil, JN Singh, VK BF Govil, JN Singh, VK TI Production of ET743, Bryostatin, and Taxol Using a Mineral Based Microbial Amplification System SO DRUG PLANTS III SE Recent Progress in Medicinal Plants LA English DT Article; Book Chapter DE Bryostatin; ET743; Taxol; Natural product; Mass spectrometry; Bacterial amplification chamber ID BRYOZOAN BUGULA-NERITINA; CANDIDATUS ENDOBUGULA SERTULA; BIOACTIVE METABOLITES; HUMIC-ACID; SYMBIONT; IDENTIFICATION; ECOSYSTEM; YEW AB Bacterial amplification chambers (BACs) are artificial media that allow marine bacteria to colonize a receptive surface. The composition of BAC's are derived from analytical measurements of an ecosystem. Marine bacteria are notoriously difficult or impossible to cultivate in a laboratory setting so a method of farming the microbes in their home environment was sought. Specifically, the BAG is left in a respective ecosystem for an extended period of time (days, weeks) and then harvested. We originally applied this to a set of marine natural products found in the Gulf of Mexico (bryostatin, ET743). From that work we adapted the methodology to the production of taxol in the Florida yew tree. We've identified six groups of chemicals that are used in constructing a BAG. (1) Trace inorganic species that may play a nutrient role (2) Organic based structures found in the sediment (3) Organic based nutrients (4) Naturally occurring polymers (5) Bulk inorganic species found in the local ecosystem (6) Components of the host organism. Preliminary results for the production of the pharmaceutical agents ET743 in Sarasota Bay (Fl) and Dickerson Bay (Fl), Taxol in Torreya State Park (Fl) and Bryostatin at Alligator Point Harbor (Fl) are discussed in this paper. C1 [Manning, Thomas J.; Bishop, Karly; McLeod, Kristen; Bullock, Gunter; Kean, Greg; Grant, Devin; Anderson, Stuart; Cooper-White, Katrice; Sermons, Shanda; Patel, Om] Valdosta State Univ, Dept Chem, Valdosta, GA 31698 USA. [Abadi, Giso] Univ Sunderland, Sunderland, Tyne & Wear, England. [Phillips, Dennis] Univ Georgia, Dept Chem, Mass Spec Facil, Athens, GA 30602 USA. [Potter, Thomas] USDA, Watershed Lab, Tifton, GA USA. [Nienow, James] Valdosta State Univ, Dept Biol, Valdosta, GA USA. [Klausmeyer, Paul; Newman, David] NCI Frederick, Nat Prod Grp, SAIC Frederick Inc, Frederick, MD USA. RP Manning, TJ (reprint author), Valdosta State Univ, Dept Chem, Valdosta, GA 31698 USA. NR 38 TC 0 Z9 0 U1 2 U2 2 PU STUDIUM PRESS LLC PI HOUSTON PA PO BOX 722200, HOUSTON, TX 77072 USA BN 978-1-933699-19-6 J9 RECENT PROG MED PLAN PY 2010 VL 29 BP 41 EP 59 PG 19 WC Plant Sciences; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA BQD66 UT WOS:000280742900004 ER PT B AU Miles, FA Sheliga, BM AF Miles, Frederick A. Sheliga, Boris M. BE Ilg, UJ Masson, GS TI Motion Detection for Reflexive Tracking SO DYNAMICS OF VISUAL MOTION PROCESSING: NEURONAL, BEHAVIORAL, AND COMPUTATIONAL APPROACHES LA English DT Article; Book Chapter ID VERGENCE EYE-MOVEMENTS; OCULAR FOLLOWING RESPONSES; VISUAL AREA MT; LATENCY DISPARITY-VERGENCE; OPTIC FLOW STIMULI; SUPERIOR TEMPORAL AREA; ULTRA-SHORT LATENCIES; TAKE-ALL MECHANISM; APPARENT-MOTION; MACAQUE MONKEY AB The moving observer who looks in the direction of heading experiences radial optic flow, which is known to elicit horizontal vergence eye movements at short latency, expansion causing convergence and contraction causing divergence: the Radial Flow Vergence Response (RFVR). The moving observer who looks off to one side experiences linear flow, which is known to elicit horizontal version eye movements at short latency: the Ocular Following Response (OFR). Although the RFVR and OFR are very different kinds of eye movement and are sensitive to very different patterns of global motion, they have very similar local spatio-temporal properties. For example, both responses are critically dependent on the Fourier composition of the motion stimuli, consistent with early spatio-temporal filtering prior to motion detection, as in the well-known energy model of motion analysis. When the motion stimuli are sine-wave gratings, the two responses share a very similar dependence on the spatial frequency and contrast of those gratings, and even the quantitative details are very similar. When the motion consists of a single step ("two-frame movie") then a brief inter-stimulus interval results in the reversal of both responses, consistent with the idea that both are mediated by motion detectors that receive a visual input whose temporal impulse response function is strongly biphasic. Further, when confronted with two sine-wave gratings that differ slightly in spatial frequency and have competing motions, both responses show nonlinear dependence on the relative contrasts of those two gratings: when the two sine waves differ in contrast by more than about an octave then the one with the higher contrast completely dominates the responses and the one with lower contrast loses its influence: winner-take-all. It has been suggested that these nonlinear interactions result from mutual inhibition between the low-level mechanisms sensing the motion of the different competing harmonics. Lastly, single unit recordings and local lesions in monkeys strongly suggest that both types of eye movements are mediated by neurons in the MT/MST region of the cerebral cortex that are sensitive to global optic flow. We will argue that these various findings are all consistent with the idea that the RFVR and OFR acquire their different global properties at the level of MT/MST, where the neurons respond to large-field radial and linear optic flow, and their shared local properties from a common earlier stage, the striate cortex, where the neurons respond to the local motion energy. C1 [Miles, Frederick A.; Sheliga, Boris M.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Miles, FA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM fam@lsr.nei.nih.gov; bms@lsr.nei.nih.gov NR 114 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0780-6 PY 2010 BP 141 EP 160 DI 10.1007/978-1-4419-0781-3_7 D2 10.1007/978-1-4419-0781-3 PG 20 WC Neurosciences SC Neurosciences & Neurology GA BMI96 UT WOS:000272519400007 ER PT B AU Lebeda, FJ Cer, RZ Stephens, R Mudunuri, U AF Lebeda, Frank J. Cer, Regina Z. Stephens, Robert Mudunuri, Uma BE Kurstot, J Forsstrom, M TI Time Course of the Effects of Botulinum Neurotoxin SO DYSTONIA: CAUSES, SYMPTOMS AND TREATMENT SE Neurology Laboratory and Clinical Research Series LA English DT Article; Book Chapter ID TOXIN TYPE-A; MOUSE NEUROMUSCULAR-JUNCTIONS; CERVICAL DYSTONIA; CLOSTRIDIAL NEUROTOXINS; DOUBLE-BLIND; MASS-SPECTROMETRY; INDUCED PARALYSIS; LIGHT-CHAIN; TRANSLOCATION; EFFICACY AB Of the seven immunologically distinct forms of the bacterial protein botulinum neurotoxin, serotypes A and B are currently the most widely used in the pharmaceutical treatment of the dystonias. In this study, we have outlined our approach in finding time-related clinical data, (e.g., onset times, durations of effect) from systematically mining the biomedical literature. These values are being integrated into mathematical frameworks to further our understanding of the therapeutic effects of the neurotoxin at the molecular and cellular levels. Potentially, these models could be of use in personalized medicine by making accurate predictions of individual patient responses to small doses of administered toxin. C1 [Lebeda, Frank J.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 20701 USA. [Cer, Regina Z.; Stephens, Robert; Mudunuri, Uma] NCI Frederick, Adv Biomed Comp Ctr, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Lebeda, FJ (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St, Ft Detrick, MD 20701 USA. NR 60 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 978-1-60876-445-7 J9 NEUROL LAB CLIN RES PY 2010 BP 179 EP 198 PG 20 WC Clinical Neurology SC Neurosciences & Neurology GA BPO29 UT WOS:000279531400007 ER PT J AU Johnson, PTJ Townsend, AR Cleveland, CC Glibert, PM Howarth, RW McKenzie, VJ Rejmankova, E Ward, MH AF Johnson, Pieter T. J. Townsend, Alan R. Cleveland, Cory C. Glibert, Patricia M. Howarth, Robert W. McKenzie, Valerie J. Rejmankova, Eliska Ward, Mary H. TI Linking environmental nutrient enrichment and disease emergence in humans and wildlife SO ECOLOGICAL APPLICATIONS LA English DT Article DE dead zones; eutryphication; global change; harmful algal blooms (HABs); host-parasite interaction; human health; nitrogen; zoonotic disease ID HARMFUL ALGAL BLOOMS; BLACK BAND DISEASE; EMERGING INFECTIOUS-DISEASES; CULEX-RESTUANS DIPTERA; GLOBAL NITROGEN-CYCLE; MARINE ECOSYSTEMS; BROWN-TIDE; LAND-USE; AMPHIBIAN MALFORMATIONS; AQUATIC EUTROPHICATION AB Worldwide increases in human and wildlife diseases have challenged ecologists to understand how large-scale environmental changes affect host-parasite interactions. One of the most profound changes to Earth's ecosystems is the alteration of global nutrient cycles, including those of phosphorus (P) and especially nitrogen (N). Along with the obvious direct benefits of nutrient application for food production, anthropogenic inputs of N and P can indirectly affect the abundance of infectious, and noninfectious pathogens. The mechanisms underpinning observed correlations, however, and how such patterns vary with disease type, have long remained conjectural. Here, we highlight recent experimental advances to critically evaluate the relationship between environmental nutrient enrichment and disease. Given the interrelated nature of human and wildlife disease emergence. we include a broad range of human and wildlife examples from terrestrial, marine, and freshwater ecosystems. We examine the consequences of nutrient pollution on directly transmitted, vector-borne, complex life cycle, and noninfectious pathogens, including West Nile virus, malaria, harmful algal blooms, coral reef diseases, and amphibian malformations. Our synthetic examination suggests that the effects of environmental nutrient enrichment on disease are complex and multifaceted, varying with the type of pathogen, host species and condition, attributes of the ecosystem, and the degree of enrichment: some pathogens increase in abundance whereas others decline or disappear. Nevertheless, available evidence indicates that ecological changes associated with nutrient enrichment often exacerbate infection and disease caused by generalist parasites with direct or simple life cycles. Observed mechanisms include changes in host/vector density, host distribution, infection resistance, pathogen virulence or toxicity, and the direct supplementation of pathogens. Collectively, these pathogens may be particularly dangerous because they can continue to cause mortality even as their hosts decline, potentially leading to sustained epidemics or chronic pathology. We suggest that interactions between nutrient enrichment and disease will become increasingly important in tropical and subtropical regions, where forecasted increases in nutrient application will occur in an environmental rich with infections pathogens. We emphasize the importance of careful disease management in conjunction with continued intensification of global nutrient cycles. C1 [Johnson, Pieter T. J.; Townsend, Alan R.; McKenzie, Valerie J.] Univ Colorado, Boulder, CO 80309 USA. [Townsend, Alan R.] Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80303 USA. [Cleveland, Cory C.] Univ Montana, Missoula, MT 59812 USA. [Glibert, Patricia M.] Univ Maryland, Ctr Environm Sci, Horn Point Lab, Cambridge, MD 21613 USA. [Howarth, Robert W.] Cornell Univ, Ithaca, NY 14853 USA. [Rejmankova, Eliska] Univ Calif Davis, Dept Environm Sci & Policy, Davis, CA 95616 USA. [Ward, Mary H.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Johnson, PTJ (reprint author), Univ Colorado, Ramaley N122,Campus Box 334, Boulder, CO 80309 USA. EM pieter.johnson@colorado.edu RI glibert, patricia/G-1026-2013 OI glibert, patricia/0000-0001-5690-1674 FU David and Lucille Packard Foundation FX P. Johnson was supported by a fellowship from the David and Lucille Packard Foundation. NR 133 TC 86 Z9 86 U1 16 U2 137 PU ECOLOGICAL SOC AMER PI WASHINGTON PA 1990 M STREET NW, STE 700, WASHINGTON, DC 20036 USA SN 1051-0761 J9 ECOL APPL JI Ecol. Appl. PD JAN PY 2010 VL 20 IS 1 BP 16 EP 29 DI 10.1890/08-0633.1 PG 14 WC Ecology; Environmental Sciences SC Environmental Sciences & Ecology GA 566GM UT WOS:000275358100003 PM 20349828 ER PT J AU Connell, N McCluskey, B AF Connell, Nancy McCluskey, Brendan BE Rappert, B TI Bringing Biosecurity-related Concepts into the Curriculum: A US View SO EDUCATION AND ETHICS IN THE LIFE SCIENCES: STRENGTHENING THE PROHIBITION OF BIOLOGICAL WEAPONS LA English DT Article; Book Chapter ID RESPONSIBLE CONDUCT; INSTRUCTION; VIRUS C1 [Connell, Nancy] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Connell, Nancy; McCluskey, Brendan] Univ Med & Dent New Jersey, Ctr BioDef, Newark, NJ 07103 USA. [Connell, Nancy] Univ Med & Dent New Jersey, Biosafety Level Facil 3, Ctr Study Emerging & Reemerging Pathogens, Newark, NJ 07103 USA. [Connell, Nancy] Univ Med & Dent New Jersey, Inst Biosafety Comm, Recombinant DNA Subcomm, Newark, NJ 07103 USA. [Connell, Nancy] NIAID, NIH, Ctr Sci Review Study, Sect HIBP, Bethesda, MD 20892 USA. [Connell, Nancy] Comm Mil Use Biol Res, Cambridge, MA USA. [Connell, Nancy] Subcomm Council Responsible Genet, Cambridge, MA USA. [McCluskey, Brendan] Univ Med & Dent New Jersey, Off Emergency Management & Occupat Hlth & Safety, Newark, NJ 07103 USA. [McCluskey, Brendan] Univ Med & Dent New Jersey, Biosafety Level Labs 3, Newark, NJ 07103 USA. [McCluskey, Brendan] Univ Med & Dent New Jersey, Chem Biol Radiol Nucl & Explos Ctr Training & Res, Newark, NJ 07103 USA. [McCluskey, Brendan] Univ Med & Dent New Jersey, Grad Sch Biomed Sci, Newark, NJ 07103 USA. RP Connell, N (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU AUSTRALIAN NATL UNIV PI CANBERRA ACT PA P O BOX 4, 2600 CANBERRA ACT, AUSTRIA BN 978-1-92166-639-1 PY 2010 BP 149 EP 161 PG 13 WC Education, Scientific Disciplines; Ethics; Medical Ethics SC Education & Educational Research; Social Sciences - Other Topics; Medical Ethics GA BVG02 UT WOS:000291435800009 ER PT J AU Greven, S Crainiceanu, C Caffo, B Reich, D AF Greven, Sonja Crainiceanu, Ciprian Caffo, Brian Reich, Daniel TI Longitudinal functional principal component analysis SO ELECTRONIC JOURNAL OF STATISTICS LA English DT Article DE Diffusion tensor imaging; functional data analysis; Karhunen-Loeve expansion; longitudinal data analysis; mixed effects model ID MIXED-EFFECTS MODELS; MULTIPLE-SCLEROSIS; SPLINE MODELS; REGRESSION; CURVES; TRACTOGRAPHY; COEFFICIENT; LESIONS; TRACT AB We introduce models for the analysis of functional data observed at multiple time points. The dynamic behavior of functional data is decomposed into a time-dependent population average, baseline (or static) subject-specific variability, longitudinal (or dynamic) subject-specific variability, subject-visit-specific variability and measurement error. The model can be viewed as the functional analog of the classical longitudinal mixed effects model where random effects are replaced by random processes. Methods have wide applicability and are computationally feasible for moderate and large datasets. Computational feasibility is assured by using principal component bases for the functional processes. The methodology is motivated by and applied to a diffusion tensor imaging (DTI) study designed to analyze differences and changes in brain connectivity in healthy volunteers and multiple sclerosis (MS) patients. An R implementation is provided. C1 [Greven, Sonja] Univ Munich, Dept Stat, D-80539 Munich, Germany. [Crainiceanu, Ciprian; Caffo, Brian] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Reich, Daniel] NIH, Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Translat Neuroradiol Unit, Bethesda, MD 20814 USA. [Reich, Daniel] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. [Reich, Daniel] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. RP Greven, S (reprint author), Univ Munich, Dept Stat, Ludwigstr 33, D-80539 Munich, Germany. EM sonja.greven@stat.uni-muenchen.de; ccrainic@jhsph.edu; bcaffo@jhsph.edu; reichds@ninds.nih.gov RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU National Institute Of Neurological Disorders And Stroke [R01NS060910]; German Research Foundation; NIH National Institute of Biomedical Imaging and Bioengineering [R01EB012547]; National Institute of Neurological Disorders and Stroke; National Multiple Sclerosis Society [TR3760A3] FX The research of Greven, Crainiceanu and Caffo was supported by Award Number R01NS060910 from the National Institute Of Neurological Disorders And Stroke. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute Of Neurological Disorders And Stroke or the National Institutes of Health.; The first author would also like to acknowledge support from the German Research Foundation through the Emmy Noether Programme.; The research of C. Crainiceanu and B. Caffo was also supported by Award Number R01EB012547 from the NIH National Institute of Biomedical Imaging and Bioengineering.; This research was supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke.; We thank the editor, David Ruppert, for his helpful comments which led to an improved version of the manuscript. The MRI scans used in Section 5 were obtained through a generous grant from the National Multiple Sclerosis Society (TR3760A3) to Dr. Peter Calabresi, whom we gratefully acknowledge. NR 52 TC 46 Z9 46 U1 1 U2 10 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1935-7524 J9 ELECTRON J STAT JI Electron. J. Stat. PY 2010 VL 4 BP 1022 EP 1054 DI 10.1214/10-EJS575 PG 33 WC Statistics & Probability SC Mathematics GA 727RJ UT WOS:000287818600039 PM 21743825 ER PT B AU Heilig, M AF Heilig, M. BE Koob, GF LeMoal, M Thompson, RF TI Alcoholism SO ENCYCLOPEDIA OF BEHAVIORAL NEUROSCIENCE, VOL 1: A-G LA English DT Article; Book Chapter ID OPIOID RECEPTOR GENE; FUNCTIONAL POLYMORPHISM; NALTREXONE RESPONSE; DEPENDENCE C1 NIAAA, Bethesda, MD 20892 USA. RP Heilig, M (reprint author), NIAAA, Bethesda, MD 20892 USA. RI koob, george/P-8791-2016; OI Heilig, Markus/0000-0003-2706-2482 NR 15 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045396-5; 978-0-08-044732-2 PY 2010 BP 34 EP 40 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BA3WW UT WOS:000335045400007 ER PT B AU Volkow, ND Baler, R AF Volkow, N. D. Baler, R. BE Koob, GF LeMoal, M Thompson, RF TI Brain Imaging and Addiction SO ENCYCLOPEDIA OF BEHAVIORAL NEUROSCIENCE, VOL 1: A-G LA English DT Article; Book Chapter ID DOPAMINE; ABUSE; METABOLISM; RECEPTORS; STRIATUM; HUMANS C1 [Volkow, N. D.] NIH, Bethesda, MD 20892 USA. [Baler, R.] Brookhaven Natl Lab, Upton, NY 11973 USA. RP Volkow, ND (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI koob, george/P-8791-2016 NR 16 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 978-0-08-045396-5; 978-0-08-044732-2 PY 2010 BP 194 EP 202 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BA3WW UT WOS:000335045400028 ER PT B AU Koob, GF Le Moal, M Thompson, RF AF Koob, George F. Le Moal, Michel Thompson, Richard F. BE Koob, GF LeMoal, M Thompson, RF TI Encyclopedia of Behavioral Neuroscience PREFACE SO ENCYCLOPEDIA OF BEHAVIORAL NEUROSCIENCE, VOL 1: A-G LA English DT Editorial Material; Book Chapter C1 [Koob, George F.] Univ Calif San Diego, Scripps Res Inst, Comm Neurobiol Addict Disorders, San Diego, CA 92103 USA. [Koob, George F.] Univ Calif San Diego, Dept Psychol, San Diego, CA 92103 USA. [Koob, George F.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Koob, George F.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Koob, George F.] Scripps Res Inst, NIAAA Alcohol Res Ctr, La Jolla, CA USA. [Koob, George F.] NIAAA, Multictr Integrat Neurosci Initiat Alcoholism, Rockville, MD USA. [Koob, George F.] Pearson Ctr Alcoholism & Addict Res, La Jolla, CA USA. [Le Moal, Michel] CALTECH, Pasadena, CA 91125 USA. [Le Moal, Michel] Salk Inst, San Diego, CA 92186 USA. [Le Moal, Michel] Scripps Res Inst, San Diego, CA USA. [Le Moal, Michel] Francois Magendie Neurosci Inst, Bordeaux, France. [Le Moal, Michel] Univ Bordeaux, Bordeaux, France. [Thompson, Richard F.] Univ So Calif, Los Angeles, CA 90089 USA. [Thompson, Richard F.] Univ So Calif, Neurosci Program, Los Angeles, CA 90089 USA. [Thompson, Richard F.] Univ Oregon, Sch Med, Eugene, OR 97403 USA. [Thompson, Richard F.] Univ Calif Irvine, Irvine, CA USA. RP Koob, GF (reprint author), Univ Calif San Diego, Scripps Res Inst, Comm Neurobiol Addict Disorders, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045396-5; 978-0-08-044732-2 PY 2010 PG 2 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BA3WW UT WOS:000335045400002 ER PT B AU Kobilo, T Potter, MC van Praag, H AF Kobilo, T. Potter, M. C. van Praag, H. BE Koob, GF LeMoal, M Thompson, RF TI Neurogenesis and Exercise SO ENCYCLOPEDIA OF BEHAVIORAL NEUROSCIENCE, VOL 2: H-O LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; ADULT NEUROGENESIS; BRAIN; NEURONS; HIPPOCAMPUS; PLASTICITY; CELLS C1 [Kobilo, T.; Potter, M. C.; van Praag, H.] NIA, Baltimore, MD 21224 USA. RP Kobilo, T (reprint author), NIA, Baltimore, MD 21224 USA. RI koob, george/P-8791-2016 NR 16 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 978-0-08-045396-5; 978-0-08-044732-2 PY 2010 BP 404 EP 409 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BA3WX UT WOS:000335059800058 ER PT B AU Koob, GF Le Moal, M Thompson, RF AF Koob, George F. Le Moal, Michel Thompson, Richard F. BE Koob, GF LeMoal, M Thompson, RF TI Encyclopedia of Behavioral Neuroscience PREFACE SO ENCYCLOPEDIA OF BEHAVIORAL NEUROSCIENCE, VOL 3: P-Z LA English DT Editorial Material; Book Chapter C1 [Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Koob, George F.] Univ Calif San Diego, Dept Psychol, San Diego, CA 92103 USA. [Koob, George F.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Koob, George F.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. [Koob, George F.] Scripps Res Inst, NIAAA, Alcohol Res Ctr, La Jolla, CA USA. [Koob, George F.] NIAAA, Multictr Integrat Neurosci Initiat Alcoholism, Rockville, MD USA. [Koob, George F.] Pearson Ctr Alcoholism & Addict Res, La Jolla, CA USA. [Le Moal, Michel] Sch Med, Bordeaux, France. [Le Moal, Michel] CALTECH, Pasadena, CA 91125 USA. [Le Moal, Michel] Salk Inst, San Diego, CA 92186 USA. [Le Moal, Michel] Scripps Res Inst, San Diego, CA USA. [Le Moal, Michel] Univ Bordeaux, Bordeaux, France. [Thompson, Richard F.] Univ So Calif, Los Angeles, CA 90089 USA. [Thompson, Richard F.] Univ So Calif, Neurosci Program, Los Angeles, CA 90089 USA. [Thompson, Richard F.] Univ Oregon, Sch Med, Eugene, OR 97403 USA. [Thompson, Richard F.] Univ Calif Irvine, Irvine, CA USA. Harvard, Boston, MA USA. [Thompson, Richard F.] Stanford, Stanford, CA USA. RP Koob, GF (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. RI koob, george/P-8791-2016 NR 0 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-045396-5; 978-0-08-044732-2 PY 2010 BP XXX EP XXXI PG 2 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BA3WY UT WOS:000335074700002 ER PT B AU Gandhy, RP Shamim, EA AF Gandhy, R. P. Shamim, E. A. BE Kompoliti, K Metman, LV TI Brainstem Reticular Myoclonus SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 1: A-G LA English DT Article; Book Chapter ID NEUROPHYSIOLOGY C1 [Gandhy, R. P.; Shamim, E. A.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Shamim, E. A.] NIH, Bethesda, MD 20892 USA. RP Gandhy, RP (reprint author), Georgetown Univ Hosp, Washington, DC 20007 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 165 EP 167 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XA UT WOS:000335076400046 ER PT B AU Shamim, EA Toro, C AF Shamim, E. A. Toro, C. BE Kompoliti, K Metman, LV TI Cortical Myoclonus SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 1: A-G LA English DT Article; Book Chapter C1 [Shamim, E. A.] Georgetown Univ Hosp, Washington, DC 20007 USA. [Shamim, E. A.; Toro, C.] NIH, Bethesda, MD 20892 USA. RP Shamim, EA (reprint author), Georgetown Univ Hosp, Washington, DC 20007 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 253 EP 254 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XA UT WOS:000335076400072 ER PT B AU Shamim, EA Toro, C AF Shamim, E. A. Toro, C. BE Kompoliti, K Metman, LV TI Cortical Tremor SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 1: A-G LA English DT Article; Book Chapter ID MYOCLONUS C1 [Shamim, E. A.] Georgetown Univ Hosp, Movement Disorders Program, Washington, DC 20007 USA. [Shamim, E. A.; Toro, C.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Shamim, EA (reprint author), Georgetown Univ Hosp, Movement Disorders Program, Washington, DC 20007 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 257 EP 258 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XA UT WOS:000335076400074 ER PT B AU Karp, BI AF Karp, B. I. BE Kompoliti, K Metman, LV TI Dystonia, Traumatic SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 1: A-G LA English DT Article; Book Chapter ID POSTTRAUMATIC MOVEMENT-DISORDERS; PERIPHERAL TRAUMA; CERVICAL DYSTONIA; INDUCE DYSTONIA; PAIN; ONSET C1 NIH, Bethesda, MD 20892 USA. RP Karp, BI (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 390 EP 393 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XA UT WOS:000335076400105 ER PT B AU Karp, BI AF Karp, B. I. BE Kompoliti, K Metman, LV TI Dystonic Storm SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 1: A-G LA English DT Article; Book Chapter ID HALLERVORDEN-SPATZ-DISEASE; LIFE-THREATENING DYSTONIA; INTRATHECAL BACLOFEN; MANAGEMENT; CHILD C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Karp, BI (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 397 EP 398 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XA UT WOS:000335076400107 ER PT B AU Karp, BI AF Karp, B. I. BE Kompoliti, K Metman, LV TI Geste Antagonistique SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 1: A-G LA English DT Article; Book Chapter ID CERVICAL DYSTONIA; SPASMODIC TORTICOLLIS; SENSORY TRICKS; PATTERNS C1 NIH, Bethesda, MD 20892 USA. RP Karp, BI (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 547 EP 549 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XA UT WOS:000335076400147 ER PT B AU Cookson, MR AF Cookson, M. R. BE Kompoliti, K Metman, LV TI PARK1, Alpha Synuclein SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 2: H-P LA English DT Article; Book Chapter ID PARKINSONS-DISEASE C1 NIA, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 379 EP 382 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XC UT WOS:000335076600116 ER PT B AU Gubitz, AK Corriveau, RA Gwinn, K AF Gubitz, A. K. Corriveau, R. A. Gwinn, K. BE Kompoliti, K Metman, LV TI Parkinsonism: Genetics SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 2: H-P LA English DT Article; Book Chapter ID PROGRESSIVE SUPRANUCLEAR PALSY; MULTIPLE SYSTEM ATROPHY; FRONTOTEMPORAL LOBAR DEGENERATION; LEWY BODIES; DEMENTIA; DISEASE; DIAGNOSIS C1 [Gubitz, A. K.] NINDS, Bethesda, MD 20892 USA. [Corriveau, R. A.] Coriell Inst Med Res, Camden, NJ USA. [Gwinn, K.] Baylor Coll Med, Houston, TX 77030 USA. RP Gubitz, AK (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 413 EP 416 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XC UT WOS:000335076600127 ER PT B AU Corriveau, RA Gubitz, AK Gwinn, K AF Corriveau, R. A. Gubitz, A. K. Gwinn, K. BE Kompoliti, K Metman, LV TI Parkinson's Disease: Genetics SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 2: H-P LA English DT Article; Book Chapter ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; JUVENILE PARKINSONISM; LRRK2 G2019S; LEWY BODIES; FAMILIES; DEMENTIA; MUTATION; FORM C1 [Corriveau, R. A.] Coriell Inst Med Res, Camden, NJ 08103 USA. [Gubitz, A. K.] NINDS, Bethesda, MD 20892 USA. [Gwinn, K.] Baylor Coll Med, Houston, TX 77030 USA. RP Corriveau, RA (reprint author), Coriell Inst Med Res, Camden, NJ 08103 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 425 EP 430 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XC UT WOS:000335076600130 ER PT B AU Luo, Y Hoffer, BJ Wang, Y AF Luo, Y. Hoffer, B. J. Wang, Y. BE Kompoliti, K Metman, LV TI Rotation, Drug-induced SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 3: Q-Z LA English DT Article; Book Chapter ID DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTOR; RATS; APOMORPHINE; AMPHETAMINE; PROTECTION; MARMOSET; BEHAVIOR C1 [Luo, Y.; Hoffer, B. J.; Wang, Y.] NIDA, Baltimore, MD 21224 USA. RP Luo, Y (reprint author), NIDA, Baltimore, MD 21224 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 49 EP 51 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XF UT WOS:000335076900016 ER PT B AU Lo, S Shamim, EA AF Lo, S. Shamim, E. A. BE Kompoliti, K Metman, LV TI Spinal Segmental Myoclonus SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 3: Q-Z LA English DT Article; Book Chapter C1 [Lo, S.; Shamim, E. A.] Georgetown Univ Hosp, Clin Fac, Washington, DC 20007 USA. [Shamim, E. A.] NIH, Bethesda, MD 20892 USA. RP Lo, S (reprint author), Georgetown Univ Hosp, Clin Fac, Washington, DC 20007 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 148 EP 148 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XF UT WOS:000335076900049 ER PT B AU Karp, BI AF Karp, B. Illowsky BE Kompoliti, K Metman, LV TI Writer's Cramp SO ENCYCLOPEDIA OF MOVEMENT DISORDERS, VOL 3: Q-Z LA English DT Article; Book Chapter ID FOCAL HAND DYSTONIA C1 NIH, Bethesda, MD 20892 USA. RP Karp, BI (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-374105-9; 978-0-12-374101-1 PY 2010 BP 340 EP 343 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BA3XF UT WOS:000335076900098 ER PT S AU Suh, I Kebebew, E AF Suh, Insoo Kebebew, Electron BE Sturgeon, C TI The Biology of Thyroid Oncogenesis SO ENDOCRINE NEOPLASIA SE Cancer Treatment and Research LA English DT Article; Book Chapter ID ACTIVATED RECEPTOR-GAMMA; POORLY DIFFERENTIATED CARCINOMAS; HISTONE DEACETYLASE INHIBITORS; TYROSINE KINASE INHIBITOR; GENE-EXPRESSION PROFILES; CANCER CELL-LINES; BRAF MUTATIONS; PAPILLARY CARCINOMAS; RET/PTC REARRANGEMENTS; TRANSGENIC MICE C1 [Kebebew, Electron] NCI, Surg Branch, Bethesda, MD 20892 USA. [Suh, Insoo] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Kebebew, E (reprint author), NCI, Surg Branch, 10 Ctr Dr,Room 4W-5952, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov NR 107 TC 5 Z9 6 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-1-4419-0856-8 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2010 VL 153 BP 3 EP 21 DI 10.1007/978-1-4419-0857-5_1 D2 10.1007/978-1-4419-0857-5 PG 19 WC Oncology SC Oncology GA BNN45 UT WOS:000275062700001 PM 19957216 ER PT S AU Shen, HCJ Libutti, SK AF Shen, Hsin-Chieh Jennifer Libutti, Steven K. BE Sturgeon, C TI The Menin Gene SO ENDOCRINE NEOPLASIA SE Cancer Treatment and Research LA English DT Article; Book Chapter ID MULTIPLE ENDOCRINE NEOPLASIA; TUMOR-SUPPRESSOR MENIN; HISTONE METHYLTRANSFERASE COMPLEX; JUND-ACTIVATED TRANSCRIPTION; DEPENDENT KINASE INHIBITORS; TYPE-1 GENE; CELL-PROLIFERATION; SOMATIC MUTATIONS; DNA-DAMAGE; NEUROENDOCRINE TUMORS C1 [Libutti, Steven K.] Montefiore Einstein Ctr Canc Care, Bronx, NY USA. [Libutti, Steven K.] Dept Surg, Bronx, NY USA. [Shen, Hsin-Chieh Jennifer] NCI, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), Dept Surg, Bronx, NY USA. EM slibutti@montefiore.org NR 89 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-1-4419-0856-8 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2010 VL 153 BP 273 EP 286 DI 10.1007/978-1-4419-0857-5_15 D2 10.1007/978-1-4419-0857-5 PG 14 WC Oncology SC Oncology GA BNN45 UT WOS:000275062700015 PM 19957230 ER PT J AU Saito, J Matsuzawa, Y Ito, H Omura, M Ito, Y Yoshimura, K Yajima, Y Kino, T Nishikawa, T AF Saito, Jun Matsuzawa, Yoko Ito, Hiroko Omura, Masao Ito, Yuzuru Yoshimura, Koichiro Yajima, Yuki Kino, Tomoshige Nishikawa, Tetsuo TI The Alkalizer Citrate Reduces Serum Uric Acid Levels and Improves Renal Function in Hyperuricemic Patients Treated with the Xanthine Oxidase Inhibitor Allopurinol SO ENDOCRINE RESEARCH LA English DT Article DE Allopurinol; Citrate preparation; Creatinine clearance; Hyperuricemia; Renal function ID VISCERAL FAT ACCUMULATION; METABOLIC SYNDROME; INSULIN-RESISTANCE; KIDNEY-DISEASE; RISK-FACTORS; GOUT; PROGRESSION; PREVENTION; INJURY; DAMAGE AB Objective. Hyperuricemia, an integral component of metabolic syndrome, is a major health problem causing gout and renal damage. Urine alkalizers such as citrate preparations facilitate renal excretion of the uric acid, but its supportive effect on xanthine oxidase inhibitors has not been tested yet. We performed a randomized, prospective study of the effect of a combination of allopurinol and a citrate preparation on renal function in patients with hyperuricemia, employing 70 patients who had hyperuricemia with serum uric acid levels >= 7.0 mg/dL, or those diagnosed as having hyperuricemia in the past. Methods. They were randomly enrolled into two study groups: the allopurinol monotherapy (MT) group or combination treatment (CT) group with allopurinol and a citrate preparation. Allopurinol (100-200 mg/day) in the absence or presence of a citrate preparation (3 g/day) was administered for 12 weeks and levels of serum uric acid, its urinary clearance (Cua), and the renal glomerular filtration rates assessed with the creatinine clearance (Ccr) were evaluated before and after the treatment. Results. Serum levels of uric acid decreased significantly in both groups, whereas the change observed was much greater in CT group. Cua was significantly increased in CT group but not in MT group. Ccr was not altered in both groups in general, whereas it was significantly increased in a fraction of CT group with decreased renal function. Conclusions. These results indicate that an additional use of citrate preparations with xanthine oxidase inhibitors is beneficial for patients with hyperuricemia, reducing circulating uric acid and improving their glomerular filtration rates. 0.5-1.0, > 1.0-2.0, > 2 [referent]), and the duration of residence within 2 miles (years categories of 10, 1-9, 0 [referent]), using logistic regression. Increased risk of NHL was observed in relation to lumber and wood products facilities (SIC 24) for the shortest distance of residential proximity (<= 0.5 mile: odds ratio [OR] = 2.2, 95% confidence interval [CI]: 0.4-11.8) or the longest duration (10 years: OR = 1.9. 95% CI: 0.8-4.8); the association with lumber facilities was more apparent for diffuse large B-cell lymphoma (lived within 2 miles: OR = 1.7, 95% CI: 1.0-3.0) than for follicular lymphoma (OR = 1.1, 95% CI: 0.5-2.2). We also observed elevated ORs for the chemical (SIC 28, 10 years: OR = 1.5,95% CI: 1.1-2.0), petroleum (SIC 29, 10 years: OR= 1.9, 95% CI: 1.0-3.6), rubber/miscellaneous plastics products (SIC 30, <= 0.5 mile: OR = 2.7, 95% CI: 1.0-7.4), and primary metal (SIC 33, lived within 2 miles: OR = 1.3, 95% CI: 1.0-1.6) industries; however, patterns of risk were inconsistent between distance and duration metrics. This study does not provide strong evidence that living near manufacturing industries increases NHL risk. However, future studies designed to include greater numbers of persons living near specific types of industries, along with fate-transport modeling of chemical releases, would be informative. (C) 2009 Elsevier Inc. All rights reserved. C1 [De Roos, A. J.; Davis, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [De Roos, A. J.; Davis, S.] Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. [Colt, J. S.; Blair, A.; Airola, M.; Hartge, P.; Nuckols, J. R.; Ward, M. H.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA. [Airola, M.] Westat Corp, Rockville, MD USA. [Severson, R. K.] Wayne State Univ, Dept Family Med, Detroit, MI USA. [Severson, R. K.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Cozen, W.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Cerhan, J. R.] Mayo Clin, Coll Med, Rochester, MN USA. [Cerhan, J. R.] Univ Iowa, Iowa City, IA USA. [Nuckols, J. R.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. RP De Roos, AJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA. EM deroos@u.washington.edu OI Cerhan, James/0000-0002-7482-178X FU National Cancer Institute [R03 CA115183]; Division of Cancer Epidemiology and Genetics of the National Cancer Institute; National Institutes of Health; Department of Health and Human Services [N01-CN-67008]; Los Angeles County [N01-CN-67010]; metropolitan areas of Seattle [N01-PC-67009]; Detroit [N01-PC-65064]; NCI-DCEG and Colorado State University FX The work of the lead author was supported by an R03 grant from the National Cancer Institute (R03 CA115183). The parent case-control study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, through contracts with four centers of the Surveillance, Epidemiology, and End Results (SEER) program in Iowa state (Contract #N01-CN-67008), Los Angeles County (#N01-CN-67010), and the metropolitan areas of Seattle (#N01-PC-67009) and Detroit (#N01-PC-65064). Support for Dr. Nuckols was provided through an IPA agreement between NCI-DCEG and Colorado State University. The research activities in the study did not begin until after informed consent was obtained from the subject. All study procedures were approved by the Institutional Review Board of the Fred Hutchinson Cancer Research Center (FHCRC Institutional Review File #6330). NR 17 TC 26 Z9 27 U1 3 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JAN PY 2010 VL 110 IS 1 BP 70 EP 78 DI 10.1016/j.envres.2009.09.011 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 548EI UT WOS:000273942000010 PM 19840879 ER PT S AU Balarezo, A Tchounwou, PB AF Balarezo, A. Tchounwou, P. B. BE Popov, V Brebbia, CA TI Acute toxicity of lead nitrate to red swamp crayfish, Procambarus clarkii SO ENVIRONMENTAL TOXICOLOGY III SE WIT Transactions on Ecology and the Environment LA English DT Proceedings Paper CT 3rd International Conference on Environmental Toxicology CY MAY 04-06, 2010 CL Limasoll, CYPRUS SP Wessex Inst Technol, WIT Transact Ecology & Env, Int Journal Sustainable Dev & Planning DE red swamp crayfish; lead nitrate; acute toxicity ID CADMIUM; EXPOSURE; COPPER; GIRARD AB Red crayfish, Procambarus clarkii, is widely farmed in the southern states of Louisiana and Texas. It is the most valuable of commercial crayfish species in the United States, where it is considered a delicacy. In recent years, its availability has decreased due to environmental contamination by toxic chemicals including lead. In the present study, we conducted a ninety-six-hour static renewal bioassay to assess the acute toxicity of lead as Pb(NO(3))(2) to adult red swamp crayfish. Study results indicated that Pb(NO(3))(2) is toxic to P. clarkii, and its toxicity is both time- and concentration-dependent. The 96-hr LC(50) was computed to be 3.95 g/L. During experimentation, erratic behaviors such as restlessness, loss of balance, air gulping, and convulsion were observed in lead-exposed crayfish. Findings from this study have provided a scientific basis for designing subsequent experiments to assess the chronic exposure and biomarkers of lead-induced toxicity in P. clarkii. C1 [Balarezo, A.; Tchounwou, P. B.] Jackson State Univ, Environm Toxicol Res Lab, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA. RP Balarezo, A (reprint author), Jackson State Univ, Environm Toxicol Res Lab, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS 39217 USA. NR 26 TC 0 Z9 0 U1 1 U2 3 PU WIT PRESS PI SOUTHAMPTON PA ASHURST LODGE, SOUTHAMPTON SO40 7AA, ASHURST, ENGLAND SN 1743-3541 BN 978-1-84564-438-3 J9 WIT TRANS ECOL ENVIR PY 2010 VL 132 BP 101 EP 107 DI 10.2495/ETOX100101 PG 7 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA BUA31 UT WOS:000288620800010 ER PT J AU Lee, HS Zhdanova, SN Vladimirtsev, VA Platonov, FA Osakovskiy, VL Subbotina, EL Broytman, O Danilova, AP Nikitina, RS Chepurnov, AA Krivoshapkin, VG Gajdusek, DC Savilov, YD Garruto, RM Goldfarb, LG AF Lee, Hee Suk Zhdanova, Svetlana N. Vladimirtsev, Vsevolod A. Platonov, Fyodor A. Osakovskiy, Vladimir L. Subbotina, Ekaterina L. Broytman, Oleg Danilova, Al'bina P. Nikitina, Raisa S. Chepurnov, Alexander A. Krivoshapkin, Vadim G. Gajdusek, D. Carleton Savilov, Yevgeniy D. Garruto, Ralph M. Goldfarb, Lev G. TI Epidemiology of Viliuisk Encephalomyelitis in Eastern Siberia SO EPIDEMIOLOGY LA English DT Article ID VILJUISK ENCEPHALOMYELITIS; ENVIRONMENT; HEREDITY; ETIOLOGY AB Background: Viliuisk encephalomyelitis is a disorder that starts, in most cases, as an acute meningoencephalitis. Survivors of the acute phase develop a slowly progressing neurologic syndrome characterized by dementia, dysarthria, and spasticity. An epidemic of this disease has been spreading throughout the Yakut Republic of the Russian Federation. Although clinical, neuropathologic, and epidemiologic data suggest infectious etiology, multiple attempts at pathogen isolation have been unsuccessful. Methods: Detailed clinical, pathologic, laboratory, and epidemiologic studies have identified 414 patients with definite Viliuisk encephalomyelitis in 15 of 33 administrative regions of the Yakut Republic between 1940 and 1999. All data are documented in a Registry. Results: The average annual Viliuisk encephalomyelitis incidence rate at the height of the epidemic reached 8.8 per 100,000 population and affected predominantly young adults. The initial outbreak occurred in a remote isolated area of the middle reaches of Viliui River; the disease spread to adjacent areas and further in the direction of more densely populated regions. The results suggest that intensified human migration from endemic villages led to the emergence of this disease in new communities. Recent social and demographic changes have presumably contributed to a subsequent decline in disease incidence. Conclusions: Based on the largest known set of diagnostically verified Viliuisk encephalomyelitis cases, we demonstrate how a previously little-known disease that was endemic in a small indigenous population subsequently reached densely populated areas and produced an epidemic involving hundreds of persons. C1 [Lee, Hee Suk; Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA. [Zhdanova, Svetlana N.; Savilov, Yevgeniy D.] E Siberian Sci Ctr, Inst Epidemiol & Microbiol, Irkutsk, Russia. [Vladimirtsev, Vsevolod A.; Platonov, Fyodor A.; Osakovskiy, Vladimir L.; Danilova, Al'bina P.; Nikitina, Raisa S.; Krivoshapkin, Vadim G.] Inst Hlth, Yakutsk, Russia. [Subbotina, Ekaterina L.; Chepurnov, Alexander A.] Inst Clin Immunol, Novosibirsk, Russia. [Broytman, Oleg] UW Madison Sch Vet Med, Madison, WI USA. [Gajdusek, D. Carleton] Inst Alfred Fessard, CNRS, Gif Sur Yvette, France. [Garruto, Ralph M.] SUNY Binghamton, Binghamton, NY USA. RP Goldfarb, LG (reprint author), NINDS, NIH, Room 4S06,5625 Fishers Lane,MSC 9404, Bethesda, MD 20892 USA. EM GoldfarbL@ninds.nih.gov FU US Department of Health and Human Services; National Institute of Neurological Disorders and Stroke, National Institutes of Health FX Supported by the BioTechnology Engagement Program of the US Department of Health and Human Services and also by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 22 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2010 VL 21 IS 1 BP 24 EP 30 DI 10.1097/EDE.0b013e3181c30fd2 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 534CK UT WOS:000272872900007 PM 20010208 ER PT J AU Ananth, CV Basso, O AF Ananth, Cande V. Basso, Olga TI Impact of Pregnancy-induced Hypertension on Stillbirth and Neonatal Mortality SO EPIDEMIOLOGY LA English DT Article ID BODY-MASS INDEX; UNITED-STATES; GESTATIONAL HYPERTENSION; GLUCOSE-INTOLERANCE; REMOTE PROGNOSIS; BLOOD-PRESSURE; FETAL-GROWTH; PREECLAMPSIA; RISK; WOMEN AB Background: Hypertensive disorders of pregnancy are more frequent in primiparous women, but may be more severe in multiparas. We examined trends in stillbirth and neonatal mortality related to pregnancy-induced hypertension (PIH), and explored whether mortality varied by parity and maternal race. Methods: We carried out a population-based study of 57 million singleton live births and stillbirths (24-46 weeks' gestation) in the United States between 1990 and 2004. We estimated rates and adjusted odds ratios (ORs) of stillbirth and neonatal death in relation to PIH, comparing births in 1990-1991 with 2003-2004. Results: PIH increased from 3.0% in 1990-1991 to 3.8% in 2003-2004. In both periods, PIH was associated with a higher risk of stillbirth and neonatal death. We explored this in more detail in 2003-2004, and observed that the increased risk of PIH-related stillbirth was higher in women having their second or higher-order births (OR = 2.2 [95% confidence interval = 2.1-2.4]) compared with women having their first birth (1.5 [1.4-1.6]). Patterns were similar for neonatal death (1.3 [1.2-1.4] in first and 1.6 [1.5-1.8] in second or higher-order births). Among multiparas, the association between PIH and stillbirth was stronger in black women (2.9 [2.7-3.2]) than white women (2.0 [1.8-2.1]). Conclusions: A substantial burden of stillbirth and neonatal mortality is associated with PIH, especially among multiparous women, which may be due to more severe PIH, or to a higher burden of underlying disease. C1 [Ananth, Cande V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, Div Epidemiol & Biostat, New Brunswick, NJ 08901 USA. [Basso, Olga] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Ananth, CV (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, Div Epidemiol & Biostat, 125 Paterson St, New Brunswick, NJ 08901 USA. EM cande.ananth@umdnj.edu RI Basso, Olga/E-5384-2010 OI Basso, Olga/0000-0001-9298-4921 FU NIH, National Institute of Environmental Health Sciences [Z01 ES044003] FX Supported, in part, by the Intramural program of the NIH, National Institute of Environmental Health Sciences (Z01 ES044003). NR 42 TC 33 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2010 VL 21 IS 1 BP 118 EP 123 DI 10.1097/EDE.0b013e3181c297af PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 534CK UT WOS:000272872900021 PM 20010214 ER PT J AU Cooney, MA Louis, GMB Sundaram, R McGuiness, BM Lynch, CD AF Cooney, Maureen A. Louis, Germaine M. Buck Sundaram, Rajeshwari McGuiness, Bridget M. Lynch, Courtney D. TI Validity of Self-reported Time to Pregnancy Response SO EPIDEMIOLOGY LA English DT Letter ID LONG-TERM RECALL; QUESTIONNAIRE C1 [Cooney, Maureen A.; Louis, Germaine M. Buck; Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. [McGuiness, Bridget M.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Lynch, Courtney D.] Ohio State Univ, Coll Med, Div Epidemiol, Columbus, OH 43210 USA. [Lynch, Courtney D.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Lynch, Courtney D.] Ohio State Univ, Coll Publ Hlth, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Lynch, Courtney D.] Ohio State Univ, Coll Publ Hlth, Dept Epidemiol, Columbus, OH 43210 USA. RP Cooney, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. EM cooneyma@.mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2010 VL 21 IS 1 BP 161 EP 161 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 534CK UT WOS:000272872900034 ER PT B AU Brown, LM Gridley, G Devesa, SS AF Brown, Linda Morris Gridley, Gloria Devesa, Susan S. BE Olshan, AF TI Descriptive Epidemiology: US Patterns SO EPIDEMIOLOGY, PATHOGENESIS AND PREVENTION OF HEAD AND NECK CANCER LA English DT Article; Book Chapter ID UNITED-STATES; HUMAN-PAPILLOMAVIRUS; CANCER; TRENDS; ADENOCARCINOMA; RATES C1 [Brown, Linda Morris] RTI Int, Rockville, MD 20852 USA. [Gridley, Gloria; Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), RTI Int, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA. EM lindabrown@rti.org; gridleyg@aol.com; devesas@mail.nih.gov NR 22 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-1-4419-1471-2 PY 2010 BP 23 EP 39 DI 10.1007/978-1-4419-1472-9_2 D2 10.1007/978-1-4419-1472-9 PG 17 WC Oncology; Pathology SC Oncology; Pathology GA BOC21 UT WOS:000276161300002 ER PT S AU Morasso, MI AF Morasso, Maria I. BE Turksen, K TI Detection of Gene Expression in Embryonic Tissues and Stratified Epidermis by In Situ Hybridization SO EPIDERMAL CELLS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE DNA; RNA; Gene expression; Epidermis; In situ hybridization ID DIFFERENTIATION AB Although recent molecular biology advances provide a very effective way in determining localized gene expression, the visualization of the expression by in situ hybridization of whole-mount embryos or paraffin-embedded tissue sections continues to be an excellent method to determine overall gene expression. In this chapter, I review protocols designed to determine mRNA expression by in situ hybridization techniques, in particular, focusing on the developing stratified epidermis. C1 NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD USA. RP Morasso, MI (reprint author), NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD USA. NR 3 TC 5 Z9 5 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 978-1-60761-379-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 585 BP 253 EP 260 DI 10.1007/978-1-60761-380-0_17 D2 10.1007/978-1-60761-380-0 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMP85 UT WOS:000273301700017 PM 19908008 ER PT B AU Dong, YQ Zou, SG AF Dong, Yuqing Zou, Sige BE Tollefsbol, TO TI Sirtuins and Aging SO EPIGENETICS OF AGING LA English DT Article; Book Chapter DE Sirtuins; Life span; Metabolism; (NAD(+))-dependent; Protein deacetylase; ADP-ribosyltransferase; Gene regulation ID LIFE-SPAN EXTENSION; CALORIE RESTRICTION MIMETICS; POLYMERASE-I TRANSCRIPTION; SMALL-MOLECULE ACTIVATORS; PROTEIN-KINASE B; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; DROSOPHILA-MELANOGASTER; DIETARY RESTRICTION; ADP-RIBOSYLTRANSFERASE AB Sirtuins are a family of highly conserved genes widely distributed in organisms ranging, from bacteria to humans. Mounting evidence has revealed the important role of sirtuins in a variety of biological processes, including transcription regulation, apoptosis, DNA repair, metabolism, and more prominently, aging. Sirtuins regulate lifespan in evolutionarily diverse species partly through modulating calorie restriction pathways. Sirtuins link the nutritional status of the cell to transcription regulation through their nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase and/or ADP-ribosyltransferase. The unique features of sirtuins make them ideal targets for discovery of prolongevity compounds or aging interventions. This chapter will review the functions of sirtuins in aging and aging interventions related to sirtuins. C1 [Zou, Sige] NIA, Funct Genom Unit, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Dong, Yuqing] Clemson Univ, Dept Biol Sci, Clemson, SC 29634 USA. RP Zou, SG (reprint author), NIA, Funct Genom Unit, Lab Expt Gerontol, Baltimore, MD 21224 USA. EM zous@grc.nia.nih.gov NR 170 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0638-0 PY 2010 BP 51 EP 75 DI 10.1007/978-1-4419-0639-7_5 D2 10.1007/978-1-4419-0639-7 PG 25 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BMQ80 UT WOS:000273356700005 ER PT J AU Fritsch, B Stott, JJ Donofrio, JJ Rogawski, MA AF Fritsch, Brita Stott, Jeffrey J. Donofrio, Joy Joelle Rogawski, Michael A. TI Treatment of early and late kainic acid-induced status epilepticus with the noncompetitive AMPA receptor antagonist GYKI 52466 SO EPILEPSIA LA English DT Article DE Status epilepticus; Kainic acid; AMPA receptor antagonist; GYKI 52466; Diazepam; Blood pressure ID REFRACTORY STATUS EPILEPTICUS; SUSTAINING STATUS EPILEPTICUS; CONVULSIVE STATUS-EPILEPTICUS; PROLONGED STATUS EPILEPTICUS; GABA(A) RECEPTORS; NEUROPROTECTIVE ACTIVITY; ANTICONVULSANT ACTIVITY; ANTIEPILEPTIC DRUGS; SEIZURE MODELS; DIAZEPAM AB P>Purpose: Benzodiazepines such as diazepam may fail to effectively treat status epilepticus because benzodiazepine-sensitive GABA(A) receptors are progressively internalized with continued seizure activity. Ionotropic glutamate receptors, including AMPA receptors, are externalized, so that AMPA receptor antagonists, which are broad-spectrum anticonvulsants, could be more effective treatments for status epilepticus. We assessed the ability of the noncompetitive AMPA receptor antagonist GYKI 52466 to protect against kainic acid-induced status epilepticus in mice. Methods: Groups of animals treated with kainic acid received GYKI 52466 (50 mg/kg followed in 15 min by 50 mg/kg) or diazepam (25 mg/kg followed in 20 min by 12.5 mg/kg) beginning at 5 min of continuous seizure activity or 25 min later. The duration of seizure activity was determined by EEG recording from epidural cortical electrodes. Results: Both GYKI 52466 and diazepam rapidly terminated electrographic and behavioral seizures when administered early. However, diazepam-treated animals exhibited more seizure recurrences. With late administration, GYKI 52466 also rapidly terminated seizures and they seldom recurred, whereas diazepam was slow to produce seizure control and recurrences were common. Although both treatments caused sedation, GYKI 52466-treated animals retained neurological responsiveness whereas diazepam-treated animals did not. GYKI 52466 did not affect blood pressure whereas diazepam caused a sustained drop in mean arterial pressure. Discussion: Noncompetitive AMPA receptor antagonists represent a promising approach for early treatment of status epilepticus; they may also be effective at later times when there is refractoriness to benzodiazepines. C1 [Fritsch, Brita; Stott, Jeffrey J.; Donofrio, Joy Joelle; Rogawski, Michael A.] Natl Inst Neurol Disorders & Stroke, Epilepsy Res Sect, NIH, Bethesda, MD USA. [Fritsch, Brita] Univ Freiburg, Dept Neurol, D-7800 Freiburg, Germany. [Rogawski, Michael A.] Univ Calif Davis, Dept Neurol, Sch Med, Sacramento, CA 95817 USA. RP Rogawski, MA (reprint author), Univ Calif Davis, Dept Neurol, Davis Sch Med, 4860 Y St,Suite 3700, Sacramento, CA 95817 USA. EM brita.fritsch@uniklinik-freiburg.de; rogawski@ucdavis.edu RI Rogawski, Michael/B-6353-2009; OI Rogawski, Michael/0000-0002-3296-8193; Donofrio, J Joelle/0000-0002-0539-8068; Fritsch, Brita/0000-0003-4884-9049 FU NINDS FX We thank Dr. Jean-Pierre Thierry for providing the noninvasive blood-pressure system and for his assistance with the acquisition of the data; Messrs. David Ide and Danny Trang for technical support; Dr. Janine Reis for commenting on the manuscript; and Den-Mat Holdings, especially Ms. Amber Touchstone, for making the Geristore (R) resin available. Dr. Brita Fritsch was supported by the NINDS Intramural Research Program. NR 59 TC 26 Z9 26 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 2010 VL 51 IS 1 BP 108 EP 117 DI 10.1111/j.1528-1167.2009.02205.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 535UE UT WOS:000272996300013 PM 19682025 ER PT B AU Theodore, WH Gaillard, WD AF Theodore, William H. Gaillard, William D. BE Fisch, BJ TI NEUROIMAGING LOCALIZING PROCEDURES SO EPILEPSY AND INTENSIVE CARE MONITORING: PRINCIPLES AND PRACTICE LA English DT Article; Book Chapter ID TEMPORAL-LOBE EPILEPSY; POSITRON-EMISSION-TOMOGRAPHY; COMPLEX PARTIAL SEIZURES; FOCAL CORTICAL DYSPLASIA; 5-HT1A RECEPTOR-BINDING; MAGNETIC-RESONANCE-SPECTROSCOPY; CEREBRAL GLUCOSE-METABOLISM; PROTON MR SPECTROSCOPY; METHYL-L-TRYPTOPHAN; REFRACTORY PARTIAL EPILEPSY C1 [Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Gaillard, William D.] Childrens Natl Med Ctr, Div Epilepsy, Dept Neurophysiol & Crit Care Neurol, Washington, DC 20010 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 181 TC 0 Z9 0 U1 1 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-933864-13-6 PY 2010 BP 355 EP 367 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BLW95 UT WOS:000271242500024 ER PT S AU Scott, I Youle, RJ AF Scott, Iain Youle, Richard J. BE Brown, GC Murphy, MP TI Mitochondrial fission and fusion SO ESSAYS IN BIOCHEMISTRY: MITOCHONDRIAL FUNCTION SE Essays in Biochemistry LA English DT Review; Book Chapter ID DYNAMIN-RELATED GTPASE; MAMMALIAN-CELLS; EMBRYONIC-DEVELOPMENT; PROTEOLYTIC CLEAVAGE; OUTER-MEMBRANE; PROTEIN OPA1; DIVISION; MORPHOLOGY; DNM1P; FTSZ AB Mitochondria are highly dynamic cellular organelles, with the ability to change size, shape and position over the course of a few seconds. Many of these changes arc related to the ability of mitochondria to undergo the highly co-ordinated processes of fission (division of a single organelle into two or more independent structures) or fusion (the opposing reaction). These actions occur simultaneously and continuously in many cell types, and the balance between them regulates the overall morphology of mitochondria within any given cell. Fission and fusion are active processes which require many specialized proteins, including mechanical enzymes that physically alter mitochondrial membranes, and adaptor proteins that regulate the interaction of these mechanical proteins with organelles. Although not fully understood, alterations in mitochondrial morphology appear to be involved in several activities that are crucial to the health of cells. In the present chapter we discuss the mechanisms behind mitochondrial fission and fusion, and discuss the implications of changes in organelle morphology during the life of a cell. C1 [Youle, Richard J.] NINDS, NIH, Bethesda, MD 20892 USA. [Scott, Iain] NHLBI, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 60 TC 25 Z9 26 U1 2 U2 12 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0071-1365 BN 978-1-85578-178-8 J9 ESSAYS BIOCHEM JI Essays Biochem. PY 2010 VL 47 BP 85 EP 98 DI 10.1042/BSE0470085 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BPO66 UT WOS:000279550900006 PM 20533902 ER PT B AU Yu, LR Stewart, NA Veenstra, TD AF Yu, Li-Rong Stewart, Nicolas A. Veenstra, Timothy D. BE Ginsburg, GS Willard, HF TI Proteomics: The Deciphering of the Functional Genome SO ESSENTIALS OF GENOMIC AND PERSONALIZED MEDICINE LA English DT Article; Book Chapter ID MASS-SPECTROMETRY; PEPTIDES; ELECTROPHORESIS; PROTEINS; SPECTRA C1 [Stewart, Nicolas A.] Strangeways Res Lab, Publ Hlth Genet Unit, Cambridge CB1 8RN, England. [Veenstra, Timothy D.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. NR 32 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 978-0-08-095811-8; 978-0-12-374934-5 PY 2010 BP 89 EP 96 DI 10.1016/B978-0-12-374934-5.00008-8 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA BID62 UT WOS:000327733200009 ER PT B AU Jain, S Singleton, AB AF Jain, Shushant Singleton, Andrew B. BE Ginsburg, GS Willard, HF TI Genetics and Genomics of Parkinson's Disease SO ESSENTIALS OF GENOMIC AND PERSONALIZED MEDICINE LA English DT Article; Book Chapter ID MITOCHONDRIAL-DNA DELETIONS; SUBSTANTIA-NIGRA NEURONS; ALPHA-SYNUCLEIN; NEURODEGENERATIVE DISEASES; RECESSIVE PARKINSONISM; FAMILIAL PARKINSONISM; LOCUS TRIPLICATION; COMPLEX DISEASE; MUTATIONS; BLOOD C1 [Singleton, Andrew B.] NIA, NIH, Neurogenet Lab, Mol Genet Unit, Bethesda, MD 20892 USA. NR 60 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 978-0-08-095811-8; 978-0-12-374934-5 PY 2010 BP 700 EP 711 DI 10.1016/B978-0-12-374934-5.00054-4 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA BID62 UT WOS:000327733200055 ER PT J AU Conroy, RS Koretsky, AP Moreland, J AF Conroy, R. S. Koretsky, A. P. Moreland, J. TI Lambda exonuclease digestion of CGG trinucleotide repeats SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE Biophysics; Single molecule; Magnetic tweezers; Lambda exonuclease; Fragile X syndrome ID DNA DIGESTION; FLUORESCENCE; INSTABILITY; SEQUENCES; DISEASE AB Fragile X syndrome and other trinucleotide diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. By use of magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and narrower distribution of rates and a higher frequency of pausing was observed. C1 [Conroy, R. S.; Koretsky, A. P.] NINCDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Conroy, R. S.; Moreland, J.] Natl Inst Stand & Technol, Boulder, CO 80305 USA. RP Conroy, RS (reprint author), NINCDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. EM conroyri@mail.nih.gov RI Conroy, Richard/D-1979-2009; Koretsky, Alan/C-7940-2015 OI Conroy, Richard/0000-0002-8896-6090; Koretsky, Alan/0000-0002-8085-4756 FU National Research Council; NINDS, NIH FX RC acknowledge the support of a National Research Council Research Associateship Award and the help of Karen Usdin and Daman Kumari of NIDDK who supplied the elongated FMR1 sequence and helped with preparation, replication and isolation of the plasmid, and Keir Neuman for critical feedback. This research was supported in part by the Intramural Research Program of the NINDS, NIH. NR 22 TC 6 Z9 6 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD JAN PY 2010 VL 39 IS 2 BP 337 EP 343 DI 10.1007/s00249-009-0502-5 PG 7 WC Biophysics SC Biophysics GA 534AT UT WOS:000272868600012 PM 19562332 ER PT J AU Ruta, L Mugno, D D'Arrigo, VG Vitiello, B Mazzone, L AF Ruta, Liliana Mugno, Diego D'Arrigo, Valentina Genitori Vitiello, Benedetto Mazzone, Luigi TI Obsessive-compulsive traits in children and adolescents with Asperger syndrome SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE Asperger syndrome; Autism; Obsessive-compulsive disorder; Repetitive behaviours; Insight ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; REPETITIVE BEHAVIOR; DIAGNOSTIC INTERVIEW; ANXIETY DISORDER; ADULTS; INDIVIDUALS; RELIABILITY; CHILDHOOD; SCHEDULE AB The objective of this study is to examine the occurrence and characteristic features of obsessive-compulsive behaviours in children and adolescents with Asperger syndrome (AS), with respect to a matched obsessive compulsive disorder group (OCD) and a typically developing control group (CG). For this purpose, 60 subjects (20 OCD; 18 AS; 22 CG), aged 8-15 years, matched for age, gender and IQ were compared. AS and OCD patients were diagnosed according to the DSM-IV-TR criteria. The Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule were used to assist in the AS diagnosis; the WISC-R was administered to assess IQ. Obsessive and compulsive symptoms were evaluated by using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). None of the AS children received a formal diagnosis of OCD. The AS group presented significantly higher frequencies of Hoarding obsessions and Repeating, Ordering and Hoarding compulsions compared to CG. The OCD group, in turn, reported significantly higher frequencies of Contamination and Aggressive obsessions and Checking compulsions compared to both the AS group and CG. As expected, the OCD group displayed a higher severity of symptoms (Moderate level of severity) than did the AS group (Mild level of severity). Finally, in our sample, neither the OCD group nor the AS group demonstrated a completely full awareness of the intrusive, unreasonable and distressing nature of symptoms, and the level of insight did not differ between the OCD group and CG, although an absence of insight was observed in the AS group. Children with AS showed higher frequencies of obsessive and compulsive symptoms than did typically developing children, and these features seem to cluster around Hoarding behaviours. Additionally, different patterns of symptoms emerged between the OCD and AS groups. Finally, in our sample, the level of insight was poor in both the OCD and the AS children. Further research should be conducted to better understand the characteristics of repetitive thoughts and behaviours in autism spectrum disorders, and to clarify the underlying neurobiological basis of these symptoms. C1 [Ruta, Liliana; Mugno, Diego; D'Arrigo, Valentina Genitori; Mazzone, Luigi] Univ Catania, Dept Paediat, Div Child Neurol & Psychiat, I-95123 Catania, Italy. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. RP Ruta, L (reprint author), Univ Catania, Dept Paediat, Div Child Neurol & Psychiat, Via S Sofia 78, I-95123 Catania, Italy. EM ruta@policlinico.unict.it; diegomugno@yahoo.it; valentina.genitori@libero.it; bvitiell@mail.nih.gov; gigimazzone@yahoo.it RI Ruta, Liliana/B-2440-2012 NR 36 TC 39 Z9 39 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD JAN PY 2010 VL 19 IS 1 BP 17 EP 24 DI 10.1007/s00787-009-0035-6 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 534AU UT WOS:000272868700002 PM 19557496 ER PT J AU Semba, RD Bandinelli, S Sun, K Guralnik, JM Ferrucci, L AF Semba, Richard D. Bandinelli, Stefania Sun, Kai Guralnik, Jack M. Ferrucci, Luigi TI Relationship of an advanced glycation end product, plasma carboxymethyl-lysine, with slow walking speed in older adults: the InCHIANTI study SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE Advanced glycation end products; Aging; Carboxymethyl-lysine; Physical performance; Walking speed ID HUMAN ARTICULAR-CARTILAGE; NONENZYMATIC GLYCATION; SKELETAL-MUSCLE; CROSS-LINKING; OXIDATIVE STRESS; COLLAGEN; SERUM; AGE; ACCUMULATION; INFLAMMATION AB Advanced glycation end products (AGEs) are bioactive molecules found in foods and generated endogenously in the body. AGEs induce cross-linking of collagen and increase the stiffness of skeletal muscle and cartilage. We characterized the relationship between a plasma AGE, carboxymethyl-lysine (CML), and slow walking speed (lowest quintile of walking speed) in older adults. Walking speed over a 4 m course was assessed in 944 adults, aged a parts per thousand yen65 years, in the InCHIANTI study, a population-based study of aging and mobility disability conducted in two towns in Tuscany, Italy. Participants in the highest quartile of plasma CML were at higher risk of slow walking speed (Odds Ratio [O.R.] 1.56, 95% Confidence Interval [C.I.] 1.02-2.38, P = 0.04) compared to those in the lower three quartiles of plasma CML in a logistic regression models adjusting for age, education, cognitive function, smoking, and chronic diseases. After exclusion of participants with diabetes, participants in the highest quartile of plasma CML were at higher risk of slow walking speed (O.R. 1.87, 95% C.I. 1.15-3.04, P = 0.01) adjusting for the same covariates. In older community-dwelling adults, elevated plasma CML is independently associated with slow walking speed. C1 [Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Dept Ophthalmol, Sch Med, Baltimore, MD 21205 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy. [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 Semba, RD (reprint author), Johns Hopkins Univ, Dept Ophthalmol, Sch Med, 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu FU National Institute on Aging [R01 AG027012, R56 AG027012, R01 AG029148]; Intramural Research Program, National Institute on Aging, NIH FX This work was supported by National Institute on Aging Grant R01 AG027012, R56 AG027012, R01 AG029148 and the Intramural Research Program, National Institute on Aging, NIH. NR 30 TC 19 Z9 20 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1439-6319 J9 EUR J APPL PHYSIOL JI Eur. J. Appl. Physiol. PD JAN PY 2010 VL 108 IS 1 BP 191 EP 195 DI 10.1007/s00421-009-1192-5 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 532XK UT WOS:000272783500020 PM 19756703 ER PT J AU Kummar, S Gutierrez, ME Gardner, ER Chen, XH Figg, WD Zajac-Kaye, M Chen, M Steinberg, SM Muir, CA Yancey, MA Horneffer, YR Juwara, L Melillo, G Ivy, SP Merino, M Neckers, L Steeg, PS Conley, BA Giaccone, G Doroshow, JH Murgo, AJ AF Kummar, Shivaani Gutierrez, Martin E. Gardner, Erin R. Chen, Xiaohong Figg, William D. Zajac-Kaye, Maria Chen, Min Steinberg, Seth M. Muir, Christine A. Yancey, Mary Ann Horneffer, Yvonne R. Juwara, Lamin Melillo, Giovanni Ivy, S. Percy Merino, Maria Neckers, Len Steeg, Patricia S. Conley, Barbara A. Giaccone, Giuseppe Doroshow, James H. Murgo, Anthony J. TI Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignancies SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Clinical trial; Phase I; 17-DMAG; Hsp90 ID SOLID TUMORS; GELDANAMYCIN; HSP90; PLASMA; 17DMAG; DOMAIN; ANALOG; 17AAG; PET AB Purpose: Phase I dose-escalation study to determine the toxicity and maximum tolerated dose (MTD) of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, administered on a twice weekly schedule in patients with advanced cancer. Experimental design 17-DMAG was administered as a 1- to 2-h infusion twice weekly in 4-week cycles. An accelerated titration design was followed until toxicity was observed, at which point standard dose-escalation proceeded. MTD was defined as the dose at which no more than one of the six patients experienced a dose-limiting toxicity (DLT). Pharmacokinetics were assessed, and Hsp70 mRNA, whose gene product is a chaperone previously shown to be upregulated following the inhibition of Hsp90, was measured in peripheral blood mononuclear cells (PBMCs). Results: A total of 31 patients received 92 courses of treatment. The MTD was 21 mg/m(2)/d; 20 patients were enrolled at this dose level. Nine patients had stable disease for a median of 4 (range 2-22) months. Both C-max and AUC increased proportionally with dose. The most common toxicities were grade 1 or 2 fatigue, anorexia, nausea, blurred vision and musculoskeletal pain. DLTs were peripheral neuropathy and renal dysfunction. Expression of Hsp70 mRNA in PBMCs was highly variable. Conclusion: Twice-weekly i.v. infusion of 17-DMAG is well tolerated, and combination phase I studies are warranted. Published by Elsevier Ltd. C1 [Kummar, Shivaani; Gutierrez, Martin E.; Chen, Xiaohong; Figg, William D.; Zajac-Kaye, Maria; Chen, Min; Steinberg, Seth M.; Muir, Christine A.; Yancey, Mary Ann; Horneffer, Yvonne R.; Merino, Maria; Neckers, Len; Steeg, Patricia S.; Conley, Barbara A.; Giaccone, Giuseppe; Doroshow, James H.; Murgo, Anthony J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Gardner, Erin R.; Juwara, Lamin; Melillo, Giovanni] NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Ivy, S. Percy; Doroshow, James H.; Murgo, Anthony J.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Kummar, S (reprint author), NCI, Ctr Canc Res, 10 Ctr Dr, Bethesda, MD 20892 USA. EM kummars@mail.nih.gov RI Figg Sr, William/M-2411-2016; Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU Division of Cancer Treatment and Diagnosis; Center for Cancer Research of the National Cancer institute; National Cancer Institute, National institutes of Health [N01-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research FX This paper was written with support from the Division of Cancer Treatment and Diagnosis and the Center for Cancer Research of the National Cancer institute. This project has been funded in part with federal funds from the National Cancer Institute, National institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This work was supported by the Intramural Research Programme of the NIH, National Cancer Institute, Center for Cancer Research. NR 28 TC 60 Z9 61 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2010 VL 46 IS 2 BP 340 EP 347 DI 10.1016/j.ejca.2009.10.026 PG 8 WC Oncology SC Oncology GA 550JE UT WOS:000274123300019 PM 19945858 ER PT J AU van Leeuwen, PJ Connolly, D Gavin, A Roobol, MJ Black, A Bangma, CH Schroder, FH AF van Leeuwen, Pim J. Connolly, David Gavin, Anna Roobol, Monique J. Black, Amanda Bangma, Chris H. Schroder, Fritz H. TI Prostate cancer mortality in screen and clinically detected prostate cancer: Estimating the screening benefit SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Prostate cancer; PSA; Screening; Mortality; Metastasis; Biopsy; Outcome; ERSPC; Early detection ID RADICAL PROSTATECTOMY; ROTTERDAM SECTION; CONTAMINATION; COUNTRIES; IMMEDIATE; DISEASE; TRENDS AB Background: To estimate the benefits of prostate-specific antigen (PSA) screening on prostate cancer (Pca) metastasis and Pca-specific mortality, we compared two populations with a well-defined difference in intensity of screening. Methods: Between 1997 and 1999, a total of 11,970 men, aged 55-74 years, were included in the intervention arm of the European Randomised Study of Screening for Prostate Cancer (ERSPC) section Rotterdam. Control population consisted of 133,287 men, aged 55-74 years, between 1998 and 1999 in Northern Ireland (NI). Men were followed for Pca incidence, Pca metastasis and cause of death until 31st December 2006. Results: Median age in both groups was 63 years at study entry (p = 0.184). In Rotterdam 94.2% of men and in NI 6% of men underwent PSA testing. In Rotterdam, 1153 men (9.6%) were diagnosed with Pca with median baseline PSA of 5.1 ng/ml. In NI, 3962 men (3.0%, p < 0.001) were diagnosed with Pca with median baseline PSA of 18.0 ng/ml (p < 0.001). The relative risk of Pca metastasis during observation in the intervention population compared to control population was 0.47 (95% confidence interval (CI), 0.35-0.63; p < 0.001). The relative risk of Pca-specific mortality was also lower in the intervention population compared to the control population after a median follow-up of 8.5 years: 0.63 (95% CI, 0.45-0.88; p = 0.008); absolute mortality reduction was 1.8 deaths per 1000 men. Conclusions: A relative reduction in Pca metastasis of 53% and Pca mortality of 37% was observed in the intervention population after 8.5 years of observation. The impact of over-diagnosis, quality of life benefits and cost-effectiveness need to be assessed before population-based PSA screening can be recommended. (C) 2009 Elsevier Ltd. All rights reserved. C1 [van Leeuwen, Pim J.; Roobol, Monique J.; Bangma, Chris H.; Schroder, Fritz H.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Connolly, David] Belfast City Hosp, Dept Urol, Belfast, Antrim, North Ireland. [Gavin, Anna] Queens Univ Belfast, No Ireland Canc Registry, Belfast BT7 1NN, Antrim, North Ireland. [Black, Amanda] NCI, Bethesda, MD 20892 USA. RP van Leeuwen, PJ (reprint author), Univ Med Ctr, Erasmus MC, Room NH 227,POB 2040, NL-3000 CA Rotterdam, Netherlands. EM p.vanleeuwen@erasmusmc.nl FU Dutch Cancer Society [KWF 94-869, 98-1657, 2002-277, 2006-3518]; Netherlands Organisation for Health Research and Development [002822820, 22000106, 50-50110-98-311]; EU [LSHC-CT-2004-503011]; Beckman Coulter Hybritech Inc.; Department of Health, Social Services & Public Safety Northern Ireland (DHSSPSNI) FX The Netherlands: The ERSPC is supported by Grants from the Dutch Cancer Society (KWF 94-869, 98-1657, 2002-277 and 2006-3518), The Netherlands Organisation for Health Research and Development (002822820, 22000106 and 50-50110-98-311), 6th Framework Program of the EU: P-Mark: LSHC-CT-2004-503011 and Beckman Coulter Hybritech Inc. and of Europe against Cancer (SOC 95 35109, SOC 96 201869 05F02, SOC 97 201329 and SOC 98 32241). The ERSPC received Erasmus MC and Ministry of Health institutional review board approval.; Northern Ireland: The Northern Ireland Cancer Registry is funded by the Department of Health, Social Services & Public Safety Northern Ireland (DHSSPSNI). NR 24 TC 35 Z9 35 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2010 VL 46 IS 2 BP 377 EP 383 DI 10.1016/j.ejca.2009.09.008 PG 7 WC Oncology SC Oncology GA 550JE UT WOS:000274123300024 PM 19804966 ER PT J AU Wade, M Baid, S Calis, K Raff, H Sinaii, N Nieman, L AF Wade, Matthew Baid, Smita Calis, Karim Raff, Hershel Sinaii, Ninet Nieman, Lynnette TI Technical details influence the diagnostic accuracy of the 1 mu g ACTH stimulation test SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PITUITARY-ADRENAL AXIS; ADRENOCORTICOTROPIN TEST; CORTISOL RESPONSE; DOSE TEST; INSUFFICIENCY; REPRODUCIBILITY; CAUTION; DISEASE; WORD AB Objective: To examine the factors causing inadequate cortisol responses to the 1 mu g ACTH stimulation test. Design: Random test assignment (by age and gender) at 0800 or 1600 h. Methods: We recruited 20 healthy adults to each of the three age groups (< 40 years, 40-55 years, and > 55 years; half females in each group). ACTH stimulation tests were performed in an outpatient clinic at the NIH Clinical Research Center. Plasma cortisol was measured just before, and 30 and 60 min after the administration of 1 mu g ACTH (1-24). The ACTH concentration in diluted and administered solutions was measured. Results: Twenty-five volunteers (19 at 1600 h) had a subnormal cortisol response (peak cortisol 10.4-17.5 mu g/dl), using a criterion < 18 mu g/dl (497 nmol/l), for a specificity of 58% (confidence interval (CI) 45-71%). Afternoon testing had a significant impact on failure rates (odds ratio 6.98, CI 2.17-22.43), while gender and age did not. The stock solution contained 1 mg ACTH, but after administration through tubing it contained only 0.5-0.8 mu g. Conclusions: The high rate of abnormal results, especially in the afternoon, and loss of ACTH through tubing suggest that morning testing and minimal tubing should be adopted to avoid an inappropriate diagnosis of adrenal insufficiency. Earlier time points and standardized protocols would facilitate comparison of studies. C1 [Wade, Matthew; Baid, Smita; Nieman, Lynnette] NICHHD, Program Reprod & Adult Endocrinol, Bethesda, MD USA. [Calis, Karim] NIH, Dept Pharm, Ctr Clin, Bethesda, MD USA. [Raff, Hershel] Med Coll Wisconsin, Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI 53226 USA. [Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD USA. RP Nieman, L (reprint author), NICHHD, Program Reprod & Adult Endocrinol, Bldg 10,CRC,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD USA. EM niemanl@nih.gov FU National Institutes of Health FX This work was supported in part by the intramural program of the National Institute of Child Health and Human Development, National Institutes of Health. NR 27 TC 34 Z9 36 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JAN PY 2010 VL 162 IS 1 BP 109 EP 113 DI 10.1530/EJE-09-0746 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 582QD UT WOS:000276611800015 PM 19797501 ER PT J AU Khan, SY Riazuddin, S Shahzad, M Ahmed, N Zafar, AU Rehman, AU Morell, RJ Griffith, AJ Ahmed, ZM Riazuddin, S Friedman, TB AF Khan, Shahid Yar Riazuddin, Saima Shahzad, Mohsin Ahmed, Nazir Zafar, Ahmad Usman Rehman, Atteeq Ur Morell, Robert J. Griffith, Andrew J. Ahmed, Zubair M. Riazuddin, Sheikh Friedman, Thomas B. TI DFNB79: reincarnation of a nonsyndromic deafness locus on chromosome 9q34.3 SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE hereditary deafness; DFNB79; DFNB33; Pakistan; chromosome 9q34.3 ID PROGRESSIVE HEARING-LOSS; RECESSIVE DEAFNESS; INNER-EAR; MUTATIONS; DOMINANT; MIR-96; MOUSE; GENE; MAPS; MICE AB Genetic analysis of an inbred Pakistani family PKDF280, segregating prelingual severe to profound sensorineural hearing loss, provided evidence for a DFNB locus on human chromosome 9q34.3. Co-segregation of the deafness trait with marker D9SH159 was determined by a two-point linkage analysis (LOD score 9.43 at theta=0). Two additional large families, PKDF517 and PKDF741, co-segregate recessive deafness with markers linked to the same interval. Haplotype analyses of these three families refined the interval to 3.84 Mb defined by D9S1818 (centromeric) and D9SH6 (telomeric). This interval overlaps with the previously reported DFNB33 locus whose chromosomal map position has been recently revised and assigned to a new position on chromosome 10p11.23-q21.1. The nonsyndromic deafness locus on chromosome 9q segregating in family PKDF280 was designated DFNB79. We are currently screening the 113 candidate DFNB79 genes for mutations and have excluded CACNA1B, EDF1, PTGDS, EHMT1, QSOX2, NOTCH1, MIR126 and MIR602. European Journal of Human Genetics (2010) 18, 125-129; doi:10.1038/ejhg.2009.121; published online 15 July 2009 C1 [Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Sect Human Genet, NIH, Rockville, MD 20850 USA. [Khan, Shahid Yar; Shahzad, Mohsin; Ahmed, Nazir; Zafar, Ahmad Usman; Rehman, Atteeq Ur; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD 20850 USA. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Sect Human Genet, NIH, 5 Res Court,Room 2A-19, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov OI Morell, Robert/0000-0003-1537-7356 FU Intramural NIH HHS [Z01 DC000039-11]; NIDCD NIH HHS [Z01 DC000039, Z01 DC000064, ZO1 DC000064, 1 ZO1 DC000039-12] NR 16 TC 6 Z9 6 U1 4 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2010 VL 18 IS 1 BP 125 EP 129 DI 10.1038/ejhg.2009.121 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 530RL UT WOS:000272609900023 PM 19603065 ER PT J AU Palker, TJ Dong, G Leitner, WW AF Palker, Thomas J. Dong, Gang Leitner, Wolfgang W. TI Mast cells in innate and adaptive immunity to infection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID BACTERIAL-INFECTIONS; NALP3 INFLAMMASOME; ACTIVATION; RECEPTORS; ADJUVANT; LUNG; MICE; RECRUITMENT; EXPRESSION; ANTIGEN C1 [Palker, Thomas J.; Leitner, Wolfgang W.] NIAID, Basic Immunol Branch, DAIT, NIH, Bethesda, MD 20892 USA. [Dong, Gang] NIAID, Asthma Allergy & Inflammat Branch, DAIT, NIH, Bethesda, MD 20892 USA. RP Palker, TJ (reprint author), NIAID, Basic Immunol Branch, DAIT, NIH, Room 6226,6610 Rockledge Dr, Bethesda, MD 20892 USA. EM palkert@niaid.nih.gov RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 NR 35 TC 7 Z9 8 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2010 VL 40 IS 1 BP 13 EP 18 PG 6 WC Immunology SC Immunology GA 549IP UT WOS:000274041800003 PM 20043290 ER PT J AU Gremel, CM Cunningham, CL AF Gremel, Christina M. Cunningham, Christopher L. TI Effects of disconnection of amygdala dopamine and nucleus accumbens N-methyl-d-aspartate receptors on ethanol-seeking behavior in mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE basolateral amygdala; conditioned place preference; conditioned reinforcement; ethanol; nucleus accumbens ID CONDITIONED PLACE PREFERENCE; MEDIAL PREFRONTAL CORTEX; BASOLATERAL AMYGDALA; EXCITOTOXIC LESIONS; PAVLOVIAN APPROACH; VENTRAL STRIATUM; MEASURING REWARD; REINFORCEMENT; COCAINE; CORE AB There is a strong interest in harnessing the genetic manipulations that are possible in mice to investigate the functional neural mechanisms modulating the associative processes that control drug-seeking behavior. However, it is unknown whether intracranial techniques, such as the disconnection procedure commonly used in rats to examine serial connectivity between implicated areas, can be successfully applied to mice. We have previously demonstrated that the expression of ethanol-seeking behavior in mice is dependent upon amygdala (Amy) dopamine and nucleus accumbens (Acb) N-methyl-d-aspartate (NMDA) receptor activation (Gremel & Cunningham, 2009). Here, we used a neuropharmacological disconnection procedure to investigate whether dopamine activation of the Amy directly leading to increases in Acb glutamate release and binding of NMDA receptors modulates the expression of ethanol-seeking behavior. Immediately before testing the expression of an ethanol-induced conditioned place preference, mice were given an Amy infusion of flupenthixol and either an ipsilateral or contralateral Acb infusion of AP-5. Although both ipsilateral and contralateral manipulations reduced the expression of ethanol conditioned place preference, in a separate experiment we demonstrated that a unilateral Acb infusion of AP-5, but not Amy flupenthixol, is sufficient to disrupt preference. The finding of a significant blockade by unilateral AP-5 into the Acb precludes any conclusions about a unique role for the Amy/Acb neuroanatomical connection in this model of ethanol-seeking behavior. Further, the current results suggest potential limitations in transferring techniques from rats to mice in order to study serial interactions between neural areas underlying motivated behaviors. Nevertheless, these findings provide evidence showing that Acb NMDA receptors play an important role in the expression of ethanol-conditioned behavior. C1 Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97201 USA. RP Gremel, CM (reprint author), NIAAA, Sect In Vivo Neural Funct, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,TS-20, Bethesda, MD 20892 USA. EM gremelc@mail.nih.gov FU NIH-NIAAA [AA016041, AA007468, AA007702] FX This research was supported by NIH-NIAAA grants AA016041, AA007468 and AA007702. Experiments within this study comply with the current laws of the USA. NR 34 TC 8 Z9 8 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2010 VL 31 IS 1 BP 148 EP 155 DI 10.1111/j.1460-9568.2009.07044.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 536SQ UT WOS:000273064500013 PM 20092560 ER PT J AU Lodish, M Patronas, NJ Stratakis, CA AF Lodish, Maya Patronas, Nicholas J. Stratakis, Constantine A. TI Reversible posterior encephalopathy syndrome associated with micronodular adrenocortical disease and Cushing syndrome SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE Cushing syndrome; Hypertension; Adrenal tumors; Hyperplasia ID LEUKOENCEPHALOPATHY SYNDROME; CLINICAL SPECTRUM; HYPERTENSION AB We report a 6-year-old girl with ACTH-independent Cushing syndrome secondary to bilateral adrenal hyperplasia; she presented with hypertension and seizures, and magnetic resonance imaging shows changes consistent with posterior reversible encephalopathy syndrome. C1 [Lodish, Maya; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet SEGEN, Program Dev Endocrinol & Genet PDEGEN, NICHD, Bethesda, MD 20892 USA. [Lodish, Maya; Stratakis, Constantine A.] NICHHD, Pediat Endocrinol Program, Program Dev Endocrinol & Genet PDEGEN, NICHD, Bethesda, MD 20892 USA. [Patronas, Nicholas J.] NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Lodish, M (reprint author), NICHHD, Sect Endocrinol & Genet SEGEN, Program Dev Endocrinol & Genet PDEGEN, NICHD, Bldg 10 CRC E,Room 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU NICHD, NIH FX This work was supported by the NICHD, NIH intramural program. NR 10 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD JAN PY 2010 VL 169 IS 1 BP 125 EP 126 DI 10.1007/s00431-009-0990-4 PG 2 WC Pediatrics SC Pediatrics GA 518VX UT WOS:000271724600021 PM 19415327 ER PT J AU Maurex, L Zaboli, G Ohman, A Asberg, M Leopardi, R AF Maurex, L. Zaboli, G. Ohman, A. Asberg, M. Leopardi, R. TI The serotonin transporter gene polymorphism (5-HTTLPR) and affective symptoms among women diagnosed with borderline personality disorder SO EUROPEAN PSYCHIATRY LA English DT Article DE Borderline personality disorder; Serotonin transporter gene polymorphism (5-HTTLPR); Depression; Obsession-compulsion; Anxiety; Suicide ID OBSESSIVE-COMPULSIVE DISORDER; STRESSFUL LIFE EVENTS; SUICIDAL-BEHAVIOR; PROMOTER POLYMORPHISM; EMOTION REGULATION; MAJOR DEPRESSION; CANDIDATE GENES; SELF-INJURY; HUMAN BRAIN; FOLLOW-UP AB Gene variants of the serotonin transporter have been associated with Vulnerability to affective disorders. In particular, the presence of one or two copies of the short (s) allele of the 5-HTTLPR polymorphism has been associated with reduced serotonin transporter expression and function, and vulnerability to affective disorders. To test for an association between variants of the serotonin transporter gene polymorphism (5-HTTLPR) and relevant clinical features of borderline personality disorder (BPD), a psychiatric disorder with symptoms characteristic for serotonin dysfunction, 77 women with BPD were genotyped in the 5-HTTLPR polymorphism. They rated their Subjective experience of borderline-specific, depressive. anxious and obsessive-compulsive symptoms, and were interviewed about lifetime incidence of suicide attempts and self-harming acts. Carriers of two s alleles of the 5-HTTLPR reported more symptoms of borderline, depression, anxiety and obsessive-compulsive behaviours, but not of suicidal and self-injury behaviour, compared to carriers of a long (l) allele. This indicates that the 5-HTTLPR ss homozygous genotype might influence serotonin function affecting susceptibility to both borderline-specific, depressive, anxious and obsessive-compulsive symptoms in BPD, and leading to a more severe symptomatology related to these clinical features. Further, this Suggests that 5-HTT gene variants may not be as influential on suicidal and self-injury behaviour in BPD. (C) 2009 Elsevier Masson SAS. All rights reserved. C1 [Maurex, L.; Ohman, A.] Karolinska Inst, Dept Clin Neurosci, Psychol Sect, S-17177 Stockholm, Sweden. [Zaboli, G.] Inst Genet & Pathol, Rudbeck Lab, Uppsala, Sweden. [Ohman, A.] Stockholm Brain Inst, Stockholm, Sweden. [Ohman, A.] Univ Florida, NIMH Ctr Res Emot & Attent, Gainesville, FL 32611 USA. [Asberg, M.] Karolinska Inst, Dept Clin Sci, S-17177 Stockholm, Sweden. [Leopardi, R.] Karolinska Inst, Dept Clin Neurosci, Sect Psychiat, S-17177 Stockholm, Sweden. [Leopardi, R.] Karolinska Inst, Ctr Mol Med, S-17177 Stockholm, Sweden. RP Maurex, L (reprint author), Karolinska Inst, Dept Clin Neurosci, Psychol Sect, S-17177 Stockholm, Sweden. EM Liselotte.Maurex@ki.se FU Stockholm County Council; Swedish Science Council; The AFA Insurance Company; Karolinska Institute FX We thank Dr Andreas Olsson for valuable language consultation. Financially supported by grants from the Stockholm County Council, the Swedish Science Council, The AFA Insurance Company and by funds from the Karolinska Institute. NR 79 TC 15 Z9 16 U1 1 U2 10 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PD JAN PY 2010 VL 25 IS 1 BP 19 EP 25 DI 10.1016/j.eurpsy.2009.05.001 PG 7 WC Psychiatry SC Psychiatry GA 549NF UT WOS:000274057100004 PM 19699062 ER PT J AU Angst, J Zimmermann, P Merikangas, K Gamma, A AF Angst, J. Zimmermann, P. Merikangas, K. Gamma, A. TI DIAGNOSIS AND COMORBIDITY: PROGRESS TOWARDS A NEW DIAGNOSTIC CLASSIFICATION OF MOOD DISORDERS SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Angst, J.; Gamma, A.] Univ Zurich, Hosp Psychiat, Dept Res, Zurich, Switzerland. [Zimmermann, P.] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Merikangas, K.] NIMH, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2010 VL 25 SU 1 PG 1 WC Psychiatry SC Psychiatry GA V21RX UT WOS:000208225800158 ER PT J AU Grigoroiu-Serbanescu, M Rietschel, M Paul, T Schulze, TG Noethen, MM Cichon, S Elston, RC AF Grigoroiu-Serbanescu, M. Rietschel, M. Paul, T. Schulze, T. G. Noethen, M. M. Cichon, S. Elston, R. C. TI TWO OR THREE AGE-OF-ONSET GROUPS IN BIPOLAR I DISORDER? FINDINGS OF COMMINGLING ANALYSIS IN ROMANIAN AND GERMAN BIPOLAR I PATIENTS SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Grigoroiu-Serbanescu, M.] Alexandru Obregia Clin Psychiat Hosp, Biometr Psychiat Genet Res Unit, Bucharest, Romania. [Rietschel, M.; Paul, T.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Schulze, T. G.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Noethen, M. M.; Cichon, S.] Univ Bonn, Inst Human Genet, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Elston, R. C.] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014 OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2010 VL 25 SU 1 PG 1 WC Psychiatry SC Psychiatry GA V21RX UT WOS:000208225801426 ER PT J AU Wolf, RC Gron, G Herrnberger, B Sambataro, F Schmid, M Vasic, N Osterfeld, ND AF Wolf, R. C. Groen, G. Herrnberger, B. Sambataro, F. Schmid, M. Vasic, N. Osterfeld, N. D. TI MAGNETIC RESONANCE IMAGING OF BASELINE BRAIN PERFUSION IN MAJOR DEPRESSIVE DISORDER SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Wolf, R. C.; Groen, G.; Herrnberger, B.; Schmid, M.; Vasic, N.; Osterfeld, N. D.] Univ Ulm, Ulm, Germany. [Sambataro, F.] NIMH, Clin Brain Disorders Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RI Sambataro, Fabio/E-3426-2010 OI Sambataro, Fabio/0000-0003-2102-416X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2010 VL 25 SU 1 PG 1 WC Psychiatry SC Psychiatry GA V21RX UT WOS:000208225800770 ER PT J AU Didon, L Roos, AB Elmberger, GP Gonzalez, FJ Nord, M AF Didon, L. Roos, A. B. Elmberger, G. P. Gonzalez, F. J. Nord, M. TI Lung-specific inactivation of CCAAT/enhancer binding protein alpha causes a pathological pattern characteristic of COPD SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Bronchiolitis; bronchopulmonary dysplasia; CCAAT/enhancer binding protein; chronic obstructive pulmonary disease; differentiation; emphysema ID OBSTRUCTIVE PULMONARY-DISEASE; C/EBP-ALPHA; BRONCHOPULMONARY DYSPLASIA; CELL-PROLIFERATION; GENE-EXPRESSION; MECHANICAL VENTILATION; ALVEOLAR SEPTATION; NEWBORN MICE; EPITHELIUM; DIFFERENTIATION AB The link between respiratory complications in prematurely born infants and susceptibility for developing chronic obstructive pulmonary disease (COPD) is receiving increasing attention. We have previously found that CCAAT/enhancer binding protein (C/EBP) activity in airway epithelial cells of COPD patients is decreased compared to healthy smokers, suggesting a previously unknown role for C/EBPs in COPD pathogenesis. To investigate the role of the transcription factor C/EBP alpha in lung development and its potential role in COPD, mice with a lung epithelial-specific disruption of the C/EBP alpha gene (Cebpa(Delta LE)) were generated using Cre-mediated excision, and the resulting pathology was studied during development and into adulthood. Cebpa(Delta LE) mice exhibit impaired lung development and epithelial differentiation, as well as affected vascularity. Furthermore, Cebpa(Delta LE) M ice that survive until adulthood develop a severe pathological picture with irregular emphysema; bronchiolitis, including goblet cell hyperplasia, bronchiolar metaplasia, fibrosis and mucus plugging; and an inflammatory cell and gene expression profile similar to COPD. Cebpa(Delta LE) mice display lung immaturity during development, and adult Cebpa(Delta LE) mice develop a majority of the histopathological and inflammatory characteristics of COPD. Cebpa(Delta LE) mice could thus provide new valuable insights into understanding the long-term consequences of lung immaturity and the link to susceptibility of developing COPD. C1 [Didon, L.] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10065 USA. [Didon, L.; Roos, A. B.; Nord, M.] Karolinska Inst, Dept Med, Div Resp Med, S-10401 Stockholm, Sweden. [Elmberger, G. P.] Karolinska Univ Hosp, Dept Pathol & Oncol, Stockholm, Sweden. [Gonzalez, F. J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Didon, L (reprint author), Weill Cornell Med Coll, Dept Med Genet, 1300 York Ave,W401, New York, NY 10065 USA. EM lud2002@med.cornell.edu FU American Thoracic Society [ATS-06-035]; Swedish Research Council - medicine [14677, 14678, 14794]; Swedish Heart-Lung Foundation [20050443]; Jeansson Foundation; Ake Wiberg Foundation; Magnus Bergvall Foundation; Konsul Th C Bergh Research Foundation; General Maternity Hospital Foundation; Karolinska Institute (Stockholm, Sweden) FX This work is supported by grants from the American Thoracic Society (grant no. ATS-06-035), the Swedish Research Council - medicine (grants 14677, 14678, 14794), the Swedish Heart-Lung Foundation (grant no. 20050443), the Jeansson, Ake Wiberg, Magnus Bergvall and Konsul Th C Bergh Research Foundations, the General Maternity Hospital Foundation and the Karolinska Institute (Stockholm, Sweden). NR 48 TC 14 Z9 14 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JAN PY 2010 VL 35 IS 1 BP 186 EP 197 DI 10.1183/09031936.00185008 PG 12 WC Respiratory System SC Respiratory System GA 549YP UT WOS:000274091300028 PM 19608583 ER PT J AU Pang, K Ryan, JF Mullikin, JC Baxevanis, AD Martindale, MQ AF Pang, Kevin Ryan, Joseph F. Mullikin, James C. Baxevanis, Andreas D. Martindale, Mark Q. CA NISC Comparative Sequencing Progra TI Genomic insights into Wnt signaling in an early diverging metazoan, the ctenophore Mnemiopsis leidyi SO EVODEVO LA English DT Article AB Background: Intercellular signaling pathways are a fundamental component of the integrating cellular behavior required for the evolution of multicellularity. The genomes of three of the four early branching animal phyla (Cnidaria, Placozoa and Porifera) have been surveyed for key components, but not the fourth (Ctenophora). Genomic data from ctenophores could be particularly relevant, as ctenophores have been proposed to be one of the earliest branching metazoan phyla. Results: A preliminary assembly of the lobate ctenophore Mnemiopsis leidyi genome generated using next-generation sequencing technologies were searched for components of a developmentally important signaling pathway, the Wnt/b-catenin pathway. Molecular phylogenetic analysis shows four distinct Wnt ligands (MlWnt6, MlWnt9, MlWntA and MlWntX), and most, but not all components of the receptor and intracellular signaling pathway were detected. In situ hybridization of the four Wnt ligands showed that they are expressed in discrete regions associated with the aboral pole, tentacle apparati and apical organ. Conclusions: Ctenophores show a minimal (but not obviously simple) complement of Wnt signaling components. Furthermore, it is difficult to compare the Mnemiopsis Wnt expression patterns with those of other metazoans. mRNA expression of Wnt pathway components appears later in development than expected, and zygotic gene expression does not appear to play a role in early axis specification. Notably absent in the Mnemiopsis genome are most major secreted antagonists, which suggests that complex regulation of this secreted signaling pathway probably evolved later in animal evolution. C1 [Pang, Kevin; Martindale, Mark Q.] Univ Hawaii Manoa, Pacific Biosci Res Ctr, Kewalo Marine Lab, Honolulu, HI 96822 USA. [Ryan, Joseph F.; Mullikin, James C.; Baxevanis, Andreas D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [NISC Comparative Sequencing Progra] NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP Martindale, MQ (reprint author), Univ Hawaii Manoa, Pacific Biosci Res Ctr, Kewalo Marine Lab, Honolulu, HI 96822 USA. EM mqmartin@hawaii.edu FU NSF Graduate Research Fellowship; NASA; NSF; National Human Genome Research Institute (National Institutes of Health) FX This work was supported by an NSF Graduate Research Fellowship to KP, NASA and NSF grants to MQM, and the Intramural Research Program of the National Human Genome Research Institute (National Institutes of Health). We thank Alice Young, Brian Schmidt, Natalie Gurson, Richelle Legaspi and Betsy Novotny, who were involved with the Mnemiopsis genomic sequencing at NISC. This manuscript was greatly improved due to the many discussions and comments from members of the Martindale Lab. Special thanks to William E. Browne and Eric Roettinger for images in Figure 1A, and the Embryology Course at the Marine Biological Laboratory (Woods Hole, MA) for summer research space. NR 64 TC 34 Z9 34 U1 1 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2041-9139 J9 EVODEVO JI EvoDevo PY 2010 VL 1 AR 10 DI 10.1186/2041-9139-1-10 PG 15 WC Evolutionary Biology; Developmental Biology SC Evolutionary Biology; Developmental Biology GA V26AD UT WOS:000208517600010 PM 20920349 ER PT J AU Ryan, JF Pang, K Mullikin, JC Martindale, MQ Baxevanis, AD AF Ryan, Joseph F. Pang, Kevin Mullikin, James C. Martindale, Mark Q. Baxevanis, Andreas D. CA NISC Comparative Sequencing Progra TI The homeodomain complement of the ctenophore Mnemiopsis leidyi suggests that Ctenophora and Porifera diverged prior to the ParaHoxozoa SO EVODEVO LA English DT Article AB Background: The much-debated phylogenetic relationships of the five early branching metazoan lineages (Bilateria, Cnidaria, Ctenophora, Placozoa and Porifera) are of fundamental importance in piecing together events that occurred early in animal evolution. Comparisons of gene content between organismal lineages have been identified as a potentially useful methodology for phylogenetic reconstruction. However, these comparisons require complete genomes that, until now, did not exist for the ctenophore lineage. The homeobox superfamily of genes is particularly suited for these kinds of gene content comparisons, since it is large, diverse, and features a highly conserved domain. Results: We have used a next-generation sequencing approach to generate a high-quality rough draft of the genome of the ctenophore Mnemiopsis leidyi and subsequently identified a set of 76 homeobox-containing genes from this draft. We phylogenetically categorized this set into established gene families and classes and then compared this set to the homeodomain repertoire of species from the other four early branching metazoan lineages. We have identified several important classes and subclasses of homeodomains that appear to be absent from Mnemiopsis and from the poriferan Amphimedon queenslandica. We have also determined that, based on lineage-specific paralog retention and average branch lengths, it is unlikely that these missing classes and subclasses are due to extensive gene loss or unusually high rates of evolution in Mnemiopsis. Conclusions: This paper provides a first glimpse of the first sequenced ctenophore genome. We have characterized the full complement of Mnemiopsis homeodomains from this species and have compared them to species from other early branching lineages. Our results suggest that Porifera and Ctenophora were the first two extant lineages to diverge from the rest of animals. Based on this analysis, we also propose a new name ParaHoxozoa - for the remaining group that includes Placozoa, Cnidaria and Bilateria. C1 [Ryan, Joseph F.; Mullikin, James C.; Baxevanis, Andreas D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Pang, Kevin; Martindale, Mark Q.] Univ Hawaii, Pacific Biosci Res Ctr, Kewalo Marine Lab, Honolulu, HI 96822 USA. [NISC Comparative Sequencing Progra] NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM andy@nhgri.nih.gov FU National Human Genome Research Institute, National Institutes of Health; NSF Graduate Research Fellowship Program; NASA; NSF FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Additional support was provided by the NSF Graduate Research Fellowship Program to KP and grants from NASA and NSF to MQM. We would like to thank Alice Young, Brian Schmidt, Natalie Gurson, Richelle Legaspi and Betsy Novotny, who were largely responsible for the sequencing work performed at NISC. JR would like to thank Arjun Prasad, Adam Reitzel, Bhavesh Borate and Tyra Wolfsberg for insightful conversations regarding this work. We are also thankful to the three anonymous reviewers whose thoughtful suggestions, corrections and insightful comments greatly improved this finished manuscript. NR 67 TC 69 Z9 69 U1 2 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2041-9139 J9 EVODEVO JI EvoDevo PY 2010 VL 1 AR 9 DI 10.1186/2041-9139-1-9 PG 18 WC Evolutionary Biology; Developmental Biology SC Evolutionary Biology; Developmental Biology GA V26AD UT WOS:000208517600009 PM 20920347 ER PT B AU Koonin, EV Wolf, YI AF Koonin, Eugene V. Wolf, Yuri I. BE Pontarotti, P TI Constraints, Plasticity, and Universal Patterns in Genome and Phenome Evolution SO EVOLUTIONARY BIOLOGY: CONCEPTS, MOLECULAR AND MORPHOLOGICAL EVOLUTION LA English DT Proceedings Paper CT 13th Evolutionary Biology Meeting CY SEP 22-25, 2009 CL Marseille, FRANCE SP Univ Provence, CNRS, GDR BIM, Conseil Gen, Ville Marseille ID SLIGHTLY DELETERIOUS MUTATIONS; CONSERVED NONCODING SEQUENCES; GENE COEXPRESSION NETWORKS; NATURAL-SELECTION; ESCHERICHIA-COLI; POSITIVE SELECTION; SYSTEMS BIOLOGY; ULTRACONSERVED ELEMENTS; CAENORHABDITIS-ELEGANS; PROTEIN EVOLUTION AB Evolutionary genomics identifies multiple constraints that differentially affect different parts of the genomes of diverse life forms. The selective pressures that shape the evolution of viral, prokaryotic, and eukaryotic genomes differ dramatically, and substantial differences exist even between animal and bacterial lineages. Constraints on protein evolution appear to be more universal and could be determined by the fundamental physics of protein folding. Some key features of the molecular phenome such as protein abundance turn out to be unexpectedly conserved and hence strongly constrained. The constraints that shape the evolution of genomes and phenomes are complemented by the plasticity and robustness of genome architecture, expression, and regulation. Several universal "laws" of genome and phenome evolution were detected, some of which seem to be dictated by selective constraints and others by neutral process. C1 [Koonin, Eugene V.; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov NR 153 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-12339-9 PY 2010 BP 19 EP 47 DI 10.1007/978-3-642-12340-5_2 PG 29 WC Evolutionary Biology SC Evolutionary Biology GA BYL29 UT WOS:000299233400002 ER PT S AU Chavakis, T AF Chavakis, Triantafyllos BE Hammes, HP Porta, M TI Interactions of Leukocytes with the Endothelium SO EXPERIMENTAL APPROACHES TO DIABETIC RETINOPATHY SE Frontiers in Diabetes LA English DT Article; Book Chapter ID JUNCTIONAL-ADHESION-MOLECULE; INFLAMMATORY CELL RECRUITMENT; PROTEIN-KINASE-C; NEUTROPHIL TRANSENDOTHELIAL MIGRATION; MONOCYTE CHEMOTACTIC PROTEIN-1; MEDIATES RAP1-INDUCED ADHESION; ISCHEMIA-REPERFUSION INJURY; HIGH GLUCOSE-CONCENTRATIONS; ICAM-1 MESSENGER-RNA; IN-VIVO AB Leukocyte recruitment is integral to both the innate and adaptive immune response. Leukocytes extravasate to sites of inflammation, injury or infection and leukocyte recruitment is crucial to a variety of inflammatory and autoimmune diseases. The process of leukocyte extravasation comprises a complex multistep cascade of adhesive interactions between leukocytes and the endothelium in the vessel wall. These adhesive events are tightly orchestrated by the crosstalk between adhesion receptors on both leukocytes and endothelial cells, as well as by several chemokine receptors, and control how different leukocyte subpopulations are recruited into specific tissues. Targeting leukocyte recruitment is of great therapeutic importance in inflammatory pathologies; specific inhibitors of leukocyte recruitment have already been used successfully in autoimmune diseases. Thus, understanding of the mechanisms regulating the leukocyte adhesion cascade as well as the tissue- and vascular bed-specific leukocyte recruitment will allow for the development of further novel therapeutic approaches with potential application in inflammatory and autoimmune diseases. The present review will (a) focus on the molecular mechanisms of the leukocyte adhesion cascade governing the interactions between leukocytes and endothelial cells and (b) address the potential role of leukocyte-endothelial interactions in the retina, and in particular, the potential role of inflammation in diabetic retinopathy. Copyright (C) 2010 S. Karger AG, Basel C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr,Rm 5B17, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov NR 186 TC 0 Z9 0 U1 3 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0251-5342 BN 978-3-8055-9275-8 J9 FRONT DIABETES JI Front.Diabetes PY 2010 VL 20 BP 158 EP 173 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BMT27 UT WOS:000273524500010 ER PT J AU Elliot, SJ Catanuto, P Espinosa-Heidmann, DG Fernandez, P Hernandez, E Saloupis, P Korach, K Karl, M Cousins, SW AF Elliot, Sharon J. Catanuto, Paola Espinosa-Heidmann, Diego G. Fernandez, Pedro Hernandez, Eleut Saloupis, Peter Korach, Kenneth Karl, Michael Cousins, Scott W. TI Estrogen receptor beta protects against in vivo injury in RPE cells SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE mouse retinal pigmented ephitelial cells; ERKO mice; estrogen receptors; extracellular matrix ID RETINAL-PIGMENT EPITHELIUM; HORMONE REPLACEMENT THERAPY; NONLETHAL OXIDANT INJURY; GENE-EXPRESSION; MACULAR DEGENERATION; REPRODUCTIVE FACTORS; DEPOSIT FORMATION; MMP-2 ACTIVATION; GROWTH; MOUSE AB Epidemiological data suggest that estrogen deficiency in postmenopausal women may contribute to the severity of AMD. We discovered that 17 beta-estradiol (E(2)) was a crucial regulator of the severity of extracellular matrix turnover (ECM) dysregulation both in vivo and in vitro. We also found in vitro that the presence of estrogen receptor (ER)beta regulates MMP-2 activity. Therefore in an attempt to delineate the role of the ER subtypes, female estrogen receptor knockout (ERKO) mice were fed a high-fat diet, and the eyes were exposed to seven 5-second doses of nonphototoxic levels of blue-green light over 2 weeks. Three months after cessation of blue light treatment, transmission electron microscopy was performed to assess severity of deposits, Bruchs membrane changes, and choriocapillaris endothelial morphology. We found that changes in the trimolecular complex of pro-MMP-2, MMP-14 and TIMP-2 correlated with increased Bruch's membrane thickening or sub-retinal deposit formation (basal laminar deposits) in ERKO beta mice. In addition RPE isolated from ERKO beta mice had an increase in expression of total collagen and a decrease in MMP-2 activity. Finally we found that ERK an intermediate signaling molecule in the MMP pathway was activated in RPE isolated from ERKO beta mice. These data suggest that mice which lack ER beta are more susceptible to in vivo injury associated with environmental light and high fat diet. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Elliot, Sharon J.; Catanuto, Paola; Fernandez, Pedro; Hernandez, Eleut] Univ Miami, Miller Sch Med, Dept Surg, Miami, FL 33136 USA. [Espinosa-Heidmann, Diego G.; Saloupis, Peter; Cousins, Scott W.] Duke Univ, Ctr Eye, Duke Ctr Macula Dis, Durham, NC USA. [Korach, Kenneth] NIH, Receptor Biol Lab, Res Triangle Pk, NC USA. [Karl, Michael] Florida Int Univ, Coll Med, Miami, FL 33199 USA. RP Elliot, SJ (reprint author), Univ Miami, Miller Sch Med, Dept Surg, Rosenstiel Med Bldg Room 1043,R104, Miami, FL 33136 USA. EM selliot@med.miami.edu OI Korach, Kenneth/0000-0002-7765-418X FU National Institutes of Health, National Eye Institute [R01 EY1447-04] FX This work was supported in part by National Institutes of Health, National Eye Institute Grant R01 EY1447-04 (SJE, MK, and SWC). NR 34 TC 14 Z9 14 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JAN PY 2010 VL 90 IS 1 BP 10 EP 16 DI 10.1016/j.exer.2009.09.001 PG 7 WC Ophthalmology SC Ophthalmology GA 542SW UT WOS:000273516500003 PM 19799898 ER PT J AU Wang, Z Do, CW Avila, MY Peterson-Yantorno, K Stone, RA Gao, ZG Joshi, B Besada, P Jeong, LS Jacobson, KA Civan, MM AF Wang, Zhao Do, Chi Wai Avila, Marcel Y. Peterson-Yantorno, Kim Stone, Richard A. Gao, Zhan-Guo Joshi, Bhalchandra Besada, Pedro Jeong, Lak Shin Jacobson, Kenneth A. Civan, Mortimer M. TI Nucleoside-derived antagonists to A(3) adenosine receptors lower mouse intraocular pressure and act across species SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE aqueous humor; servo-null micropipette system; pneumotonometry; nucleoside-based antagonists; bovine nonpigmented ciliary epithelial cells ID CILIARY EPITHELIAL-CELLS; NORMAL-TENSION GLAUCOMA; ACTIVATED CL-CHANNELS; SELECTIVE ANTAGONISTS; HIGHLY POTENT; AGONISTS; MODULATION; DISCOVERY; LIGANDS AB The purpose of the study was to determine whether novel, selective antagonists of human A(3) adenosine receptors (ARs) derived from the A(3)-selective agonist Cl-IB-MECA lower intraocular pressure (IOP) and act across species. IOP was measured invasively with a micropipette by the Servo-Null Micropipette System (SNMS) and by non-invasive pneumotonometry during topical drug application. Antagonist efficacy was also assayed by measuring inhibition of adenosine-triggered shrinkage of native bovine nonpigmented ciliary epithelial (NPE) cells. Five agonist-based A(3)AR antagonists lowered mouse IOP measured with SNMS tonometry by 3-5 mm Hg within minutes of topical application. Of the five agonist derivatives, LJ 1251 was the only antagonist to lower IOP measured by pneumotonometry. No effect was detected pneumotonometrically over 30 min following application of the other four compounds, consonant with slower, smaller responses previously measured non-invasively following topical application of A(3)AR agonists and the dihydropyridine A(3)AR antagonist MRS 1191. Latanoprost similarly lowered SNMS-measured IOP, but not IOP measured non-invasively over 30 min. Like MRS 1191, agonist-based A(3)AR antagonists applied to native bovine NPE cells inhibited adenosine-triggered shrinkage. In summary, the results indicate that antagonists of human A(3)ARs derived from the potent, selective A3 agonist Cl-IB-MECA display efficacy in mouse and bovine cells, as well. When intraocular delivery was enhanced by measuring mouse IOP invasively, five derivatives of the A(3)AR agonist Cl-IB-MECA lowered IOP but only one rapidly reduced IOP measured non-invasively after topical application. We conclude that derivatives of the highly-selective A(3)AR agonist Cl-IB-MECA can reduce IOP upon reaching their intraocular target, and that nucleoside-based derivatives are promising A(3) antagonists for study in multiple animal models. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Wang, Zhao; Avila, Marcel Y.; Peterson-Yantorno, Kim; Civan, Mortimer M.] Univ Penn, Dept Physiol, Sch Med, Philadelphia, PA 19104 USA. [Do, Chi Wai] Hong Kong Polytech Univ, Sch Optometry, Hong Kong, Hong Kong, Peoples R China. [Stone, Richard A.] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Gao, Zhan-Guo; Joshi, Bhalchandra; Besada, Pedro; Jacobson, Kenneth A.] NIDDK, NIH, Bethesda, MD USA. [Jeong, Lak Shin] Ewha Womans Univ, Coll Pharm, Seoul, South Korea. [Civan, Mortimer M.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Civan, MM (reprint author), Univ Penn, Dept Physiol, Sch Med, Richards Bldg, Philadelphia, PA 19104 USA. EM civan@mail.med.upenn.edu RI Besada Pereira, Pedro/E-6051-2012; Jacobson, Kenneth/A-1530-2009; Wang, Zhao/C-2168-2014; OI Besada Pereira, Pedro/0000-0002-9985-9063; Jacobson, Kenneth/0000-0001-8104-1493; WANG, ZHAO/0000-0002-4233-9884 FU National Institutes of Health [EY01583]; Paul and Evanina Bell Mackall Foundation Trust; Research to Prevent Blindness; Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases; [EY13624] FX Supported in part by research grant EY13624 (MMC) and core grant EY01583 from the National Institutes of Health, the Paul and Evanina Bell Mackall Foundation Trust (RAS) and Research to Prevent Blindness (RAS). BVJ and KAJ acknowledge support from the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. NR 36 TC 27 Z9 27 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JAN PY 2010 VL 90 IS 1 BP 146 EP 154 DI 10.1016/j.exer.2009.10.001 PG 9 WC Ophthalmology SC Ophthalmology GA 542SW UT WOS:000273516500020 PM 19878673 ER PT J AU Lathia, JD Chigurupati, S Thundyil, J Selvaraj, PK Mughal, MR Woodruff, TM Chan, SL Karamyan, VT Mattson, MP Arumugam, TV AF Lathia, Justin D. Chigurupati, Srinivasulu Thundyil, John Selvaraj, Pradeep K. Mughal, Mohamed R. Woodruff, Trent M. Chan, Sic L. Karamyan, Vardan T. Mattson, Mark P. Arumugam, Thiruma V. TI Pivotal role for beta-1 integrin in neurovascular remodelling after ischemic stroke SO EXPERIMENTAL NEUROLOGY LA English DT Article DE beta 1 integrin; Cerebral ischemia; Angiogenesis; Vascular remodelling; Endothelial cells ID ENDOTHELIAL GROWTH-FACTOR; CEREBRAL-ARTERY OCCLUSION; BLOOD-BRAIN-BARRIER; ENHANCES ANGIOGENESIS; FACTOR EXPRESSION; CELL-ADHESION; INTEGRINS; MICE; RAT; ANGIOPOIETIN-1 AB beta 1 integrin is a cell surface molecule that is critical for endothelial cell adhesion, migration and survival during angiogenesis. In the present study we employed in vivo and in vitro models to elucidate the role of beta 1 integrin in vascular remodelling and stroke outcomes. At 24 h after cerebral ischemia and reperfusion (I/R), the ischemic cortex (ipsilateral area) exhibited modest beta 1 integrin immunoreactivity and a robust increase was observed at 72 h. Double-label immunohistochemical analysis for beta 1 integrin with neuronal (NeuN). microglial (Iba-1), astrocyte (GFAP), progenitor cell (Ng2) and blood vessel (collagen 4) markers showed that beta 1 integrin expression only localized to blood vessels. In vitro studies using cultured endothelial cells and a beta 1 integrin blocking antibody confirmed that beta 1 integrin is required for endothelial cell migration, proliferation and blood vessel formation. In vivo studies in the cerebral I/R model using the beta 1 integrin blocking antibody further confirmed that beta 1 integrin signaling is involved in vascular formation and recovery following ischemic stroke. Finally, we found that beta 1 integrin is critically involved in functional deficits and survival after a stroke. These results Suggest that beta 1 integrin plays important roles in neurovascular remodelling and functional outcomes following stroke, and that targeting the beta 1 integrin signalling may provide a novel strategy for modulating angiogenesis in ischemic stroke and other pathological conditions. (C) 2009 Elsevier Inc. All rights reserved. C1 [Thundyil, John; Woodruff, Trent M.; Arumugam, Thiruma V.] Univ Queensland, Sch Biomed Sci, St Lucia, Qld 4072, Australia. [Lathia, Justin D.; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Lathia, Justin D.] Cleveland Clin, Dept Stem Cell Biol & Regenerat Med, Lerner Res Inst, Cleveland, OH 44195 USA. [Chigurupati, Srinivasulu; Chan, Sic L.] Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32816 USA. [Thundyil, John; Selvaraj, Pradeep K.; Karamyan, Vardan T.] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. RP Arumugam, TV (reprint author), Univ Queensland, Sch Biomed Sci, St Lucia, Qld 4072, Australia. EM t.arumugam@uq.edu.au RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; Woodruff, Trent/B-4861-2009 OI Woodruff, Trent/0000-0003-1382-911X FU National Institutes of Health (NIH); American Heart Association FX This research was Supported by the National Institute on Aging Intramural Research Program of the National Institutes of Health (NIH) and American Heart Association (to T.V.A.). NR 42 TC 13 Z9 14 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2010 VL 221 IS 1 BP 107 EP 114 DI 10.1016/j.expneurol.2009.10.007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 546RH UT WOS:000273827500013 PM 19837065 ER PT J AU Madan, RA Mohebtash, M Schlom, J Gulley, JL AF Madan, Ravi A. Mohebtash, Mahsa Schlom, Jeffrey Gulley, James L. TI Therapeutic vaccines in metastatic castration-resistant prostate cancer: principles in clinical trial design SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE clinical trial design; immunotherapy; prostate cancer; therapeutic cancer vaccine ID REGULATORY T-CELLS; IMMUNOLOGICAL SELF-TOLERANCE; ANDROGEN-DEPRIVATION THERAPY; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; COSTIMULATORY MOLECULES; RADICAL PROSTATECTOMY; BREAST-CANCER; DENDRITIC CELLS; LUNG-CANCER AB Although docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer in 2004, additional therapies are still required. Prostate cancer is often slow-growing and expresses many tumor-associated antigens, making it a feasible target for immunotherapy. Several therapeutic cancer vaccines have been developed for prostate cancer, including antigen-presenting-cell-based, vector-based, and whole tumor cell vaccines. initial trials demonstrated that vaccine approaches have limited toxicity. Clinical trials of targeted biologic therapies have demonstrated that patient selection is vital, and there is preliminary evidence that clinical parameters can be used to encompass metastatic prostate cancer patients who will more probably respond to vaccine treatment. In addition to appropriate patient selection, a successful clinical trial must have an appropriate primary endpoint as well. Three randomized, 'placebo'-controlled studies in metastatic castration-resistant prostate cancer have suggested a clinically significant survival advantage in spite of a lack of improvement in time to progression, implying that overall survival is the ideal endpoint for such trials. Careful examination of data from completed immunotherapy clinical trials in prostate cancer has identified appropriate patient populations and endpoints. Those principles need to be applied to future trial design to properly evaluate prostate cancer vaccines. C1 [Gulley, James L.] NCI, Clin Trials Grp, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. [Madan, Ravi A.; Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Clin Trials Grp, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 81 TC 20 Z9 20 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 EI 1744-7682 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD JAN PY 2010 VL 10 IS 1 BP 19 EP 28 DI 10.1517/14712590903321421 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 542HF UT WOS:000273482900002 PM 19857185 ER PT J AU Pasha, S Gupta, K AF Pasha, Santosh Gupta, Kshitij TI Various drug delivery approaches to the central nervous system SO EXPERT OPINION ON DRUG DELIVERY LA English DT Review DE blood-brain barrier; brain targeting; central nervous system; colloidal nanosystems; convection-enhanced delivery; delivery approaches ID BLOOD-BRAIN-BARRIER; CONVECTION-ENHANCED DELIVERY; SOLID LIPID NANOPARTICLES; PEGYLATED LIPOSOMAL DOXORUBICIN; CELL-PENETRATING PEPTIDES; VECTOR-MEDIATED STRATEGY; ALZHEIMERS-DISEASE; RAT-BRAIN; PROTEIN TRANSDUCTION; ENDOTHELIAL-CELLS AB Importance of the field. The presence of the blood-brain barrier (BBB), an insurmountable obstacle, in particular, and other barriers in brain and periphery contribute to hindrance of the successful diagnosis and treatment of a myriad of central nervous system pathologies. This review discusses several strategies adopted to define a rational drug delivery approach to the CNS along with a short description of the strategies implemented by the authors' group to enhance the analgesic activity, a CNS property, of chimeric peptide of Met-enkephalin and FMRFa (YGGFMKKKFMRFa-YFa). Areas covered in this review. Various approaches for drug delivery to the CNS with their beneficial and non-beneficial aspects, supported by an extensive literature Survey published recently, up to August 2009. What the reader will gain: The reader will have the privilege of gaining an understanding of previous as well as recent approaches to breaching the CNS barriers. Take home message: Among the various strategies discussed, the potential for efficacious CNS drug targeting in future lies either with the non-invasively administered multifunctional nanosystems or these nanosystems without characterstics such as long systemic circulating capability and avoiding reticuloendothelial system scavenging system of the body, endogenous transporters and efflux inhibitors administered by convection-enhanced delivery. C1 [Pasha, Santosh] Inst Genom & Integrat Biol, Peptide Synth Lab, Delhi 110007, India. [Gupta, Kshitij] NCI, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA. RP Pasha, S (reprint author), Inst Genom & Integrat Biol, Peptide Synth Lab, Mall Rd, Delhi 110007, India. EM spasha@igib.res.in; guptak@mail.nih.gov RI Ganju, Shahji/F-3409-2012 FU Council of Scientific & Industrial Research (CSIR) [NWP0013] FX The authors received financial support from Council of Scientific & Industrial Research (CSIR) project NCL-IGIB JCI (NWP0013). NR 139 TC 18 Z9 18 U1 0 U2 15 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5247 J9 EXPERT OPIN DRUG DEL JI Expert Opin. Drug Deliv. PD JAN PY 2010 VL 7 IS 1 BP 113 EP 135 DI 10.1517/17425240903405581 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 546QM UT WOS:000273825300009 PM 20017662 ER PT J AU Lebeda, FJ Cer, RZ Stephens, RM Mudunuri, U AF Lebeda, Frank J. Cer, Regina Z. Stephens, Robert M. Mudunuri, Uma TI Temporal characteristics of botulinum neurotoxin therapy SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE antigenicity; decay; diffusion; duration; immunogenicity; onset; persistence; spread; waning ID TOXIN TYPE-A; TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; ACADEMY-OF-NEUROLOGY; PROSPECTIVE OPEN-LABEL; CERVICAL DYSTONIA; DOUBLE-BLIND; CLOSTRIDIAL NEUROTOXINS; NEUROMUSCULAR-JUNCTION; GLABELLAR WRINKLES; MASS-SPECTROMETRY AB Botulinum neurotoxin is a pharmaceutical treatment used for an increasing number of neurological and non-neurological indications, symptoms and diseases. Despite the wealth of clinical reports that involve the timing of the therapeutic effects of this toxin, few studies have attempted to integrate these data into unified models. Secondary reactions have also been examined including the development of adverse events, resistance to repeated applications, and nerve terminal sprouting. Our primary intent for conducting this review was to gather relevant pharmacodynamic data from suitable biomedical literature regarding botulinum neurotoxins via the use of automated data-mining techniques. We envision that mathematical models will ultimately be of value to those who are healthcare decision makers and providers, as well as clinical and basic researchers. Furthermore, we hypothesize that the combination of this computer-intensive approach with mathematical modeling will predict the percentage of patients who will favorably or adversely respond to this treatment and thus will eventually assist in developing the increasingly important area of personalized medicine. C1 [Lebeda, Frank J.] USA, Med Res & Mat Command, Combat Casualty Care Res Program, Ft Detrick, MD 21702 USA. [Cer, Regina Z.; Stephens, Robert M.; Mudunuri, Uma] NCI, Adv Biomed Comp Ctr, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Lebeda, FJ (reprint author), USA, Med Res & Mat Command, Combat Casualty Care Res Program, 504 Scott St, Ft Detrick, MD 21702 USA. EM frank.lebeda@amedd.army.mil; cerr@mail.nih.gov; stephensr@mail.nih.gov; mudunuriu@mail.nih.gov FU Defense Threat Reduction Agency Joint Science and Technology Office-Chemical Biological Defense [3.10043-07-RD-B]; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported by the Defense Threat Reduction Agency Joint Science and Technology Office-Chemical Biological Defense [project 3.10043-07-RD-B] to Frank J Lebeda; and by the National Cancer Institute, National Institutes of Health, under contract No. HHSN261200800001E. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the US Army. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services. 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. NR 75 TC 8 Z9 9 U1 1 U2 8 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD JAN PY 2010 VL 10 IS 1 BP 93 EP 103 DI 10.1586/ERN.09.134 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 572ZF UT WOS:000275876800016 PM 20021324 ER PT J AU Bukreyev, A Collins, PL AF Bukreyev, Alexander Collins, Peter L. TI Filovirus vaccines: what challenges are left? SO EXPERT REVIEW OF VACCINES LA English DT Editorial Material ID PROTECTS NONHUMAN-PRIMATES; STOMATITIS-VIRUS VECTORS; EBOLA HEMORRHAGIC-FEVER; MARBURG VIRUS; POSTEXPOSURE PROTECTION; RHESUS-MONKEYS; GUINEA-PIGS; INFECTION; IMMUNITY; TRANSMISSION C1 [Bukreyev, Alexander; Collins, Peter L.] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bukreyev, A (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 50 South Dr,Room 6505, Bethesda, MD 20892 USA. EM abukreyev@niaid.nih.gov; pcollins@niaid.nih.gov FU Intramural NIH HHS NR 35 TC 3 Z9 3 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD JAN PY 2010 VL 9 IS 1 BP 5 EP 8 DI 10.1586/ERV.09.150 PG 4 WC Immunology SC Immunology GA 544JA UT WOS:000273650800002 PM 20021298 ER PT J AU Ananth, S Jonas, W AF Ananth, Sita Jonas, Wayne TI IMPLEMENTING OHES SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING LA English DT Editorial Material C1 [Jonas, Wayne] Georgetown Univ, Med Ctr, Washington, DC 20057 USA. [Jonas, Wayne] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Jonas, Wayne] NIH, Off Alternat Med, Bethesda, MD 20892 USA. [Jonas, Wayne] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. [Jonas, Wayne] WHO Collaborating Ctr Tradit Med, New York, NY USA. NR 3 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-8307 J9 EXPLORE-NY JI Explore-J Sci. Heal. PD JAN-FEB PY 2010 VL 6 IS 1 BP 52 EP 53 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 590FH UT WOS:000277209600010 PM 20129313 ER PT S AU Klinman, D Klaschik, S AF Klinman, Dennis Klaschik, Sven BE Kikuchi, Y Rykova, EY TI Modulation and Regulation of Gene Expression by CpG Oligonucleotides SO EXTRACELLULAR NUCLEIC ACIDS SE Nucleic Acids and Molecular Biology LA English DT Article; Book Chapter ID PLASMACYTOID DENDRITIC CELLS; TOLL-LIKE RECEPTORS; INDUCED IMMUNE ACTIVATION; DOUBLE-STRANDED-RNA; BACTERIAL-DNA; B-CELL; CUTTING EDGE; INDUCTION; MACROPHAGES; MOTIFS AB Immune cells are triggered when their Toll-like receptors (TLR) interact with pathogen-associated molecular patterns present on infectious agents. For example, TLR9 recognizes unmethylated CpG motifs present in bacterial DNA, whereas TLR3 recognizes single-stranded RNA present in viruses. Microarrays were used to examine the pattern of gene activation elicited following engagement of TLR9 and TLR3. Two distinct waves of activation were induced by CpG DNA. Each wave was regulated by a small group of major and minor inducers. Included in these waves of gene activation were suppressive networks that served to then downregulate TLR-dependent cellular stimulation. Triggering via TLR3 activated a larger and more complex regulatory network than did TLR9. Synergy was observed when cells were stimulated with both TLRs. This was characterized by the early and persistent activation of multiple regulatory pathways, resulting in a prolonged signaling cascade that increased, magnified, and diversified gene expression. C1 [Klinman, Dennis; Klaschik, Sven] NCI Frederick, Natl Canc Inst, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Klinman, D (reprint author), NCI Frederick, Natl Canc Inst, Canc & Inflammat Program, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov NR 52 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0933-1891 BN 978-3-642-12616-1 J9 NUCLEIC ACIDS MOL BI JI Nucleic Acids Molec. Biol. PY 2010 VL 25 BP 191 EP 208 DI 10.1007/978-3-642-12617-8_11 D2 10.1007/978-3-642-12617-8 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQH18 UT WOS:000281000900011 ER PT B AU Motabar, O Goldin, E Zheng, W Sidransky, E AF Motabar, Omid Goldin, Ehud Zheng, Wei Sidransky, Ellen BE Elstein, D Altarescu, G Beck, M TI Small Molecule Drug Discovery for Fabry Disease SO FABRY DISEASE LA English DT Article; Book Chapter DE Fabry disease; alpha-galactosidase; Drug discovery; High throughput screening; Small molecule chaperone therapy; Assay optimization ID ENZYME REPLACEMENT THERAPY; ALPHA-GALACTOSIDASE-A; GAUCHER-DISEASE; CHAPERONE THERAPY; PHARMACOLOGICAL ENHANCEMENT; BETA-GLUCOSIDASE; GLOBOTRIAOSYLCERAMIDE; CHROMATOGRAPHY; GLYCOSIDASES; FIBROBLASTS AB Small molecule therapy has been widely used for the treatment of a variety of diseases. Small molecule drugs can be easily administered to patients, and are advantageous in that they can cross the blood-brain barrier, do not cause autoimmune responses, and have lower manufacturing costs. In this chapter, we focus on different strategies and methods for small molecule drug development as it applies to Fabry disease. The steps involved in developing an appropriate high throughput screen to identify activators and inhibitors of alpha galactosidase A are outlined. Assay development includes optimization of the assay pH, time course, enzyme and substrate concentration and the amount of sodium taurocholate used. The assay must then be validated and confirmed using additional screens. The optimized screens can be used to identify novel lead compounds that can serve as new starting points for drug development for Fabry disease. C1 [Motabar, Omid; Goldin, Ehud; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Zheng, Wei] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM motabaro@mail.nih.gov; goldine@mail.nih.gov; wzheng@mail.nih.gov; sidranse@mail.nih.gov NR 39 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-9032-4 PY 2010 BP 163 EP 177 DI 10.1007/978-90-481-9033-1_9 D2 10.1007/978-90-481-9033-1 PG 15 WC Genetics & Heredity; Medicine, General & Internal SC Genetics & Heredity; General & Internal Medicine GA BQO46 UT WOS:000281448000009 ER PT J AU Mittal, J Hummer, G AF Mittal, Jeetain Hummer, Gerhard TI Interfacial thermodynamics of confined water near molecularly rough surfaces SO FARADAY DISCUSSIONS LA English DT Article ID HYDROPHOBIC SURFACES; HYDROPHILIC SURFACES; DYNAMICS SIMULATIONS; LENGTH SCALES; LIQUID WATER; SHORT-RANGE; FORCE; TRANSITION; NANOTUBES; CHEMISTRY AB We study the effects of nanoscopic roughness on the interfacial free energy of water confined between solid surfaces. SPC/E water is simulated in confinement between two infinite planar surfaces that differ in their physical topology: one is smooth and the other one is physically rough on a sub-nanometre length scale. The two thermodynamic ensembles considered, with constant pressure either normal or parallel to the walls, correspond to different experimental conditions. We find that molecular-scale surface roughness significantly increases the solid liquid interfacial free energy compared to the smooth surface. For our surfaces with a water-wall interaction energy minimum of -1.2 kcal mol(-1), we observe a transition from a hydrophilic surface to a hydrophobic surface at a roughness amplitude of about 3 angstrom and a wavelength of 11.6 angstrom, with the interfacial free energy changing sign from negative to positive. In agreement with previous studies of water near hydrophobic surfaces, we find an increase in the isothermal compressibility of water with increasing surface roughness. Interestingly, average measures of the water density and hydrogen-bond number do not contain distinct signatures of increased hydrophobicity. In contrast, a local analysis indicates transient dewetting of water in the valleys of the rough surface, together with a significant loss of hydrogen bonds, and a change in the dipole orientation toward the surface. These microscopic changes in the density, hydrogen bonding, and water orientation contribute to the large increase in the interfacial free energy, and the change from a hydrophilic to a hydrophobic character of the surface. C1 [Mittal, Jeetain] Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. [Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Mittal, J (reprint author), Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. EM jeetain@lehigh.edu; hummer@helix.nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS [ZIA DK029036-04] NR 62 TC 54 Z9 54 U1 0 U2 37 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1364-5498 J9 FARADAY DISCUSS JI Faraday Discuss. PY 2010 VL 146 BP 341 EP 352 DI 10.1039/b925913a PG 12 WC Chemistry, Physical SC Chemistry GA 651DG UT WOS:000281904200026 PM 21043431 ER PT J AU Raifman, O Kolusheva, S Comin, MJ Kedei, N Lewin, NE Blumberg, PM Marquez, VE Jelinek, R AF Raifman, Or Kolusheva, Sofiya Comin, Maria J. Kedei, Noemi Lewin, Nancy E. Blumberg, Peter M. Marquez, Victor E. Jelinek, Raz TI Membrane anchoring of diacylglycerol lactones substituted with rigid hydrophobic acyl domains correlates with biological activities SO FEBS JOURNAL LA English DT Article DE biomimetic membranes; diacylglycerol; diacylglycerol lactones (DAG-lactones); membrane interactions; PKC translocation ID PROTEIN-KINASE-C; CONFORMATIONALLY CONSTRAINED ANALOGS; LIPID VESICLES; DAG-LACTONES; ASSAY; DELTA; SELECTIVITY; ALPHA AB Synthetic diacylglycerol lactones (DAG lactones) are effective modulators of critical cellular signaling pathways downstream of the lipophilic second messenger diacylglycerol that activate a host of protein kinase C (PKC) isozymes as well as other non-kinase proteins that share with PKC similar C1 membrane-targeting domains. A fundamental determinant of the biological activity of these amphiphilic molecules is the nature of their interactions with cellular membranes. This study characterizes the membrane interactions and bilayer anchoring of a series of DAG lactones in which the hydrophobic moiety is a 'molecular rod', namely a rigid 4-[2-(R-phenyl)ethynyl]benzoate moiety in the acyl position. Use of assays employing chromatic biomimetic vesicles and biophysical techniques revealed that the mode of membrane anchoring of the DAG lactone derivatives was markedly affected by the presence of the hydrophobic diphenyl rod and by the size of the functional unit at the terminus of the rod. Two primary mechanisms of interaction were observed: surface binding of the DAG lactones at the lipid/water interface and deep insertion of the ligands into the alkyl core of the lipid bilayer. These membrane-insertion properties could explain the different patterns of the PKC translocation from the cytosol to membranes that is induced by the molecular-rod DAG lactones. This investigation emphasizes that the side residues of DAG lactones, rather than simply conferring hydrophobicity, profoundly influence membrane interactions, and thus may further contribute to the diversity of biological actions of these synthetic biomimetic ligands. C1 [Comin, Maria J.; Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Raifman, Or; Kolusheva, Sofiya; Jelinek, Raz] Ben Gurion Univ Negev, Dept Chem, Beer Sheva, Israel. [Kedei, Noemi; Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, 376 Boyles St, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov; razj@bgu.ac.il RI JELINEK, RAZ/F-2023-2012; OI jelinek, raz/0000-0002-0336-1384 FU US National Institutes of Health, Center for Cancer Research, National Cancer Institute FX We are grateful to Dr L. Meshi and Dr E. Nativ-Roth for help with the cryo-TEM experiments. This research was supported in part by the Intramural Research Program of the US National Institutes of Health, Center for Cancer Research, National Cancer Institute. NR 26 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JAN PY 2010 VL 277 IS 1 BP 233 EP 243 DI 10.1111/j.1742-4658.2009.07477.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 533PG UT WOS:000272836100023 PM 19961537 ER PT J AU Calvo, E Tokumasu, F Mizurini, DM McPhie, P Narum, DL Ribeiro, JMC Monteiro, RQ Francischetti, IMB AF Calvo, Eric Tokumasu, Fuyuki Mizurini, Daniella M. McPhie, Peter Narum, David L. Ribeiro, Jose Marcos C. Monteiro, Robson Q. Francischetti, Ivo M. B. TI Aegyptin displays high-affinity for the von Willebrand factor binding site (RGQOGVMGF) in collagen and inhibits carotid thrombus formation in vivo SO FEBS JOURNAL LA English DT Article DE aegyptin; blood-sucking; GPVI; thrombosis; yellow fever ID INDUCED PLATELET-AGGREGATION; GLYCOPROTEIN-VI; SPECIFICALLY BINDS; ADHESION PROTEINS; SALIVARY-GLANDS; MOUSE MODEL; ACTIVATION; RECEPTOR; INTEGRIN; COAGULATION AB Aegyptin is a 30 kDa mosquito salivary gland protein that binds to collagen and inhibits platelet aggregation. We have studied the biophysical properties of aegyptin and its mechanism of action. Light-scattering plot showed that aegyptin has an elongated monomeric form, which explains the apparent molecular mass of 110 kDa estimated by gel-filtration chromatography. Surface plasmon resonance identified the sequence RGQOGVMGF (where O is hydroxyproline) that mediates collagen interaction with von Willebrand factor (vWF) as a high-affinity binding site for aegyptin, with a K(D) of approximately 5 nm. Additionally, aegyptin interacts with the linear peptide RGQPGVMGF and heat-denatured collagen, indicating that the triple helix and hydroxyproline are not a prerequisite for binding. However, aegyptin does not interact with scrambled RGQPGVMGF peptide. Aegyptin also recognizes the peptides (GPO)(10) and GFOGER with low affinity (mu m range), which respectively represent glycoprotein VI and integrin alpha 2 beta 1 binding sites in collagen. Truncated forms of aegyptin were engineered, and the C-terminus fragment was shown to interact with collagen and to attenuate platelet aggregation. In addition, aegyptin prevents laser-induced carotid thrombus formation in the presence of Rose Bengal in vivo, without significant bleeding in rats. In conclusion, aegyptin interacts with distinct binding sites in collagen, and is useful tool to inhibit platelet-collagen interaction in vitro and in vivo. C1 [Calvo, Eric; Ribeiro, Jose Marcos C.; Francischetti, Ivo M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20852 USA. [Tokumasu, Fuyuki] NIAID, Malaria Genet Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20852 USA. [Mizurini, Daniella M.; Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil. [McPhie, Peter] NIDDK, Lab Biochem & Genet, NIDDKD, NIH, Bethesda, MD USA. [Narum, David L.] NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20852 USA. RP Francischetti, IMB (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E-28, Bethesda, MD 20852 USA. EM ifrancischetti@niaid.nih.gov RI Inbeb, Inct/K-2317-2013; Monteiro, Robson/B-8007-2014; OI Tokumasu, Fuyuki/0000-0003-2790-1071; Calvo, Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We are thankful to the Department of Transfusional Medicine at the National Institutes of Health Clinical Center for providing fresh platelet-rich plasma. We are grateful to Dr Jan Lukszo [ Peptide Synthesis and Analysis Laboratory, Research Technologies Branch, National Institute of Allergy and Infectious Diseases ( NIAID)/NIH] for assistance with peptide synthesis, and Karine Reiter for assistance with analytical SEC-MALSHPLC. We are thankful to Drs Joan C. Marini and Wayne Cabral [ National Institute of Child Health and Human Development ( NICHD)/NIH] and Michael B. Murphy ( GE Healthcare/Biacore) for helpful discussions. E. C., F. T., P. M., D. N., J. M. C. R. and I. M. B. F. are US government employees. NR 53 TC 22 Z9 22 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JAN PY 2010 VL 277 IS 2 BP 413 EP 427 DI 10.1111/j.1742-4658.2009.07494.x PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 541EF UT WOS:000273396000016 PM 20015075 ER PT J AU Vincent, K Kennedy, S Stratton, P AF Vincent, Katy Kennedy, Stephen Stratton, Pamela TI Pain scoring in endometriosis: entry criteria and outcome measures for clinical trials. Report from the Art and Science of Endometriosis meeting SO FERTILITY AND STERILITY LA English DT Article DE Endometriosis; pain; quality of life; dysmenorrhea ID QUALITY-OF-LIFE; PELVIC PAIN; IMMPACT RECOMMENDATIONS; WOMEN; QUESTIONNAIRE; SEVERITY; SYMPTOMS; THERAPY; DANAZOL AB Standardized entry criteria and outcome measures for clinical trials in endometriosis-related pain would facilitate the comparison of trial results and the production of systematic reviews, improving evidence-based practice in this area. This report summarizes the recommendations from an international meeting for these criteria. (Fertil Steril(R) 2010;93:62-7. (C)2010 by American Society for Reproductive Medicine.) C1 [Vincent, Katy; Kennedy, Stephen] John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England. [Stratton, Pamela] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Vincent, K (reprint author), John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Headley Way, Oxford OX3 9DU, England. EM kvincent@fmrib.ox.ac.uk FU National Institute of Child Health and Human Development; Ferring; Neurocrine; Pfizer; Schering; Takeda; TAP Pharmaceuticals FX This study was supported by the Intramural Program of the National Institute of Child Health and Human Development and unrestricted educational grants from Ferring, Neurocrine, Pfizer, Schering, Takeda, and TAP Pharmaceuticals. NR 25 TC 33 Z9 35 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN 1 PY 2010 VL 93 IS 1 BP 62 EP 67 DI 10.1016/j.fertnstert.2008.09.056 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 543TJ UT WOS:000273601200011 PM 18990378 ER PT J AU Csokmay, JM Yauger, BJ Henne, MB Armstrong, AY Queenan, JT Segars, JH AF Csokmay, John M. Yauger, Belinda J. Henne, Melinda B. Armstrong, Alicia Y. Queenan, John T. Segars, James H. TI Cost analysis model of outpatient management of ovarian hyperstimulation syndrome with paracentesis: "Tap early and often" versus hospitalization SO FERTILITY AND STERILITY LA English DT Article DE Ovarian hyperstimulation syndrome; OHSS; paracentesis; cost-analysis; outpatient management; ART; cost ID INVITRO FERTILIZATION; SYNDROME OHSS; FLUID; PREVENTION; ASPIRATION; ASCITES AB Objective: To compare the cost of two treatment regimens for moderate to severe ovarian hyperstimulation syndrome (OHSS): conservative inpatient versus outpatient management with paracentesis. Design: A decision-tree mathematical model comparing conservative inpatient versus outpatient management of moderate to severe OHSS was created. The common final pathway of either management was resolution of OHSS. Sensitivity analyses were performed over the range of variables. Main Outcome Measure(s): Total management cost of OHSS. Result(s): The cost of conservative therapy including first-tier complications was $10,099 (range $9,655-$15,044). The cost of outpatient management with paracentesis was $1954 (range $788-$12,041). This resulted in an estimated cost savings of $8145 with outpatient management with paracentesis. One-way sensitivity analyses were performed. Varying the probability of admission after outpatient treatment still indicated that outpatient treatment was the most cost-effective (probability = 1.0, cost = $6110). Varying the duration of hospitalization with primary inpatient treatment was equal to outpatient treatment costs only at a stay of 0.71 days or shorter. Conclusion(s): Our model suggests early outpatient paracentesis for moderate to severe OHSS is the most cost-effective management plan when compared with traditional conservative inpatient therapy. The cost savings for outpatient management persisted throughout a variety of outcome probabilities. (Fertil Steril(R) 2010;93:167-73. (C)2010 by American Society for Reproductive Medicine.) C1 [Csokmay, John M.; Yauger, Belinda J.; Henne, Melinda B.; Armstrong, Alicia Y.; Segars, James H.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Queenan, John T.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Csokmay, John M.; Yauger, Belinda J.; Armstrong, Alicia Y.; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. RP Segars, JH (reprint author), NICHD, NIH, 10 Ctr Dr,Bldg 10,CRC,1E-3140, Bethesda, MD USA. EM segarsj@mail.nih.gov FU Reproductive Biology and Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This research was supported in part by the Intramural Research Program of the Reproductive Biology and Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 20 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN 1 PY 2010 VL 93 IS 1 BP 167 EP 173 DI 10.1016/j.fertnstert.2008.09.054 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 543TJ UT WOS:000273601200026 PM 18990389 ER PT J AU Pollack, AZ Louis, GMB Sundaram, R Lum, KJ AF Pollack, Anna Z. Louis, Germaine M. Buck Sundaram, Rajeshwari Lum, Kirsten J. TI Caffeine consumption and miscarriage: a prospective cohort study SO FERTILITY AND STERILITY LA English DT Editorial Material ID SPONTANEOUS-ABORTION; DELAYED CONCEPTION; PREGNANCY; RISK; REGRESSION; BEVERAGES; OUTCOMES AB Caffeine consumption has been equivocally associated with miscarriage, despite an absence of prospective longitudinal measurement of caffeine intake during sensitive windows of human development. In response to this critical data gap, we analyzed daily caffeine consumption while attempting pregnancy through 12 menstrual cycles at risk for pregnancy and found that caffeine consumption did not increase the risk or hazard of miscarriage, even after adjusting for relevant covariates. (Fertil Steril(R) 2010;93:304-6. (C)2010 by American Society for Reproductive Medicine.) C1 [Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. [Sundaram, Rajeshwari; Lum, Kirsten J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. [Pollack, Anna Z.] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Rm 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov RI Pollack, Anna/F-2021-2011; OI Pollack, Anna/0000-0002-4313-3298; Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural NIH HHS [Z99 HD999999] NR 25 TC 8 Z9 8 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN 1 PY 2010 VL 93 IS 1 BP 304 EP 306 DI 10.1016/j.fertnstert.2009.07.992 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 543TJ UT WOS:000273601200049 PM 19732873 ER PT J AU Fejzo, MS Romero, R Goodwin, TM AF Fejzo, Marlena S. Romero, Roberto Goodwin, T. Murphy TI Patients with a history of hyperemesis gravidarum have similar symptoms during egg stimulation and develop ovarian hyperstimulation syndrome: case series SO FERTILITY AND STERILITY LA English DT Editorial Material DE Hyperemesis gravidarum; ovarian hyperstimulation syndrome; surrogacy; fertility ID PREGNANCY; NAUSEA; RISK AB Objective: To investigate the symptoms and outcomes of ovarian stimulation in patients with a history of hyperemesis gravidarum. Design: Retrospective case series. Setting: Research laboratory of a university hospital. Patient(s): Participants in an ongoing study on hyperemesis gravidarum that reported ovarian stimulation for gestational surrogacy. Intervention(s): Review of medical records. Main Outcome Measure(s): Pregnancy history, symptoms, estradiol level and mature oocyte number in cases, and nausea and vomiting level reported in surrogate. Result(s): Three cases in their early thirties with a history of hyperemesis gravidarum presented with severe nausea and vomiting during ovarian stimulation and ovarian hyperstimulation syndrome. Gestational carriers reported normal nausea and vomiting of pregnancy. Conclusion(s): This series provides lessons for in vitro fertilization for cases with a history of hyperemesis gravidarum and their gestational carriers as well as insight into the cause of hyperemesis gravidarum and its potential role in fertility. A link between hyperemesis gravidarum and an evolutionary advantage of increased fertility suggests a novel theory to explain the selection for nausea and vomiting in pregnancy. (Fertil Steril (R) 2010;93:267.e9-e11. (C)2010 by American Society for Reproductive Medicine.) C1 [Fejzo, Marlena S.; Goodwin, T. Murphy] Univ Calif Los Angeles, Dept Maternal Fetal Med, Keck Sch Med, Los Angeles, CA USA. [Romero, Roberto] NICHHD, NIH, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI USA. RP Fejzo, MS (reprint author), 675 Charles E Young Dr S,5535 MRL Bldg, Los Angeles, CA 90095 USA. EM mfejzo@mednet.ucla.edu FU National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services FX Supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services. NR 14 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN 1 PY 2010 VL 93 IS 1 AR 267.e9 DI 10.1016/j.fertnstert.2009.09.022 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 668RQ UT WOS:000283287700004 PM 19878938 ER PT B AU Tuchman, M Gahl, WA Gunay-Aygun, M AF Tuchman, Maya Gahl, William A. Gunay-Aygun, Meral BE Murray, KF Larson, AM TI Genetics of Fibrocystic Diseases of the Liver and Molecular Approaches to Therapy SO FIBROCYSTIC DISEASES OF THE LIVER LA English DT Article; Book Chapter DE Hepatorenal fibrocystic disease; Polycystic liver disease; Congenital hepatic fibrosis; Caroli's syndrome; Caroli's disease; Polycystic kidney disease; Primary cilia; Centrosome; Nephronophthisis; Joubert syndrome; and related disorders; COACH; Meckel syndrome; Bardet-Biedl syndrome; Polycystin 1; Polycystin 2; Fibrocystin; Hepatocystin; Sec63; EGFR-TKI; inhibitors; Src-inhibitors; Rapamycin; Somatostatin inhibitors ID POLYCYSTIC KIDNEY-DISEASE; BARDET-BIEDL-SYNDROME; MECKEL-GRUBER-SYNDROME; HEPATIC-PANCREATIC DYSPLASIA; ASPHYXIATING THORACIC DYSTROPHY; CHOLANGIOCYTE PRIMARY CILIA; CHAPERONIN-LIKE PROTEIN; DIGITAL SYNDROME TYPE-1; HUMAN OBESITY SYNDROME; RENAL CYSTIC-DISEASE AB Congenital hepatic fibrosis (CHF), Caroli's disease (CD), and polycystic liver disease (PLD) are the three major descriptive categories of fibrocystic liver disease. Caroli's syndrome (CS) and CD probably represent different presentations of the same continuum. CS refers to CD in association with CHF. CHF/CS and PLD are often part of multisystem disorders associated with fibrocystic renal involvement. These are collectively referred to as "ciliopathies," since the abnormal proteins involved function on the primary cilium or its basal body. The inheritance pattern of CHF/CS is autosomal recessive, with rare exceptions such as the CHF associated with X-linked oral-facial-digital syndrome type 1. The inheritance pattern of PLD is autosomal dominant; the majority of patients have autosomal dominant polycystic kidney disease (ADPKD) caused by mutations in the PKD1 or PKD2 genes. Autosomal dominant polycystic liver disease (ADPLD), in which PLD is not associated with renal cysts, refers to a genetically distinct entity caused by mutations in the PRKCSH or SEC63 genes. CHF/CS most commonly presents in association with autosomal recessive polycystic kidney disease (ARPI(D) caused by mutations in the PKHD1 gene. Multisystem syndromes associated with CHF/CS include Meckel, Bardet Biedl, and Joubert syndromes and related cerebello-hepatorenal syndromes, renal-hepatic-pancreatic-dysplasia, and ciliary skeletal dysplasias such as Jeune's chondrodysplasia. Many syndromic ciliopathies display marked genotypic heterogeneity with multiple different genes causing the same disease. This chapter will review the molecular genetic bases of these disorders and provide an overview of novel targeted therapies. C1 [Tuchman, Maya; Gahl, William A.; Gunay-Aygun, Meral] NHGRI, Med Genet Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Tuchman, M (reprint author), NHGRI, Med Genet Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 141 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 978-1-60327-523-1 PY 2010 BP 71 EP 102 DI 10.1007/978-1-60327-524-8_4 D2 10.1007/978-1-60327-524-8 PG 32 WC Medicine, General & Internal; Surgery; Urology & Nephrology SC General & Internal Medicine; Surgery; Urology & Nephrology GA BOL05 UT WOS:000276922600005 ER PT B AU Parisi, MA Finn, LS Glass, IA AF Parisi, Melissa A. Finn, Laura S. Glass, Ian A. BE Murray, KF Larson, AM TI Meckel and Joubert Syndromes SO FIBROCYSTIC DISEASES OF THE LIVER LA English DT Article; Book Chapter DE Meckel syndrome; Joubert syndrome; Molar tooth sign; Nephronophthisis; Ductal plate malformation; Ciliary disorder; Ciliopathy; Congenital hepatic fibrosis; Encephalocele; Cerebellar vermis hypoplasia ID SYNDROME-RELATED DISORDERS; MOLAR TOOTH SIGN; FAMILIAL JUVENILE NEPHRONOPHTHISIS; RECESSIVE MENTAL-RETARDATION; CONGENITAL HEPATIC-FIBROSIS; INTRAHEPATIC BILE-DUCTS; BARDET-BIEDL-SYNDROME; OCULO-RENAL SYNDROMES; SENIOR-LOKEN-SYNDROME; AHI1 GENE-MUTATIONS AB Both Meckel (Gruber) syndrome (MKS; MIM 249000) and Joubert syndrome and related disorders (JSRD; MIM 213300) are rare, autosomal recessive genetic disorders that share congenital malformations of the posterior fossa or the hindbrain and are associated with defects in the structure and/or the function of the primary cilium. The cardinal features of Meckel syndrome include the triad of brain anomalies (usually an occipital encephalocele), cystic renal dysplasia, and hepatic ductal plate malformation, in conjunction with a variety of other more variable malformations, such as polydactyly. MKS is typically lethal in the perinatal period. The genetic defects in MKS involve at least five genes that localize to the primary cilium and/or the basal body. Joubert syndrome and related disorders are characterized by a complex hindbrain malformation identified on axial magnetic resonance imaging (MRI) known as the molar tooth sign (MTS), as well as intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other congenital anomalies, including retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis, have been described. In contrast to MKS, most children with this condition survive infancy to reach adulthood. At least seven genes cause JSRD, with the MKS3 gene more likely to be associated with hepatic fibrosis and the JSRD subtype known as COACH syndrome. In fact, the JSRD genes associated with liver (and other) phenotypes overlap with the MKS genes, illustrating the close association of these two disorders and their shared etiology in coding for proteins important in the function of the primary cilium. C1 [Parisi, Melissa A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. [Finn, Laura S.] Univ Washington, Sch Med, Dept Labs, Seattle, WA USA. [Finn, Laura S.; Glass, Ian A.] Seattle Childrens Hosp, Seattle, WA USA. [Glass, Ian A.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. RP Parisi, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. NR 144 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 978-1-60327-523-1 PY 2010 BP 221 EP 256 DI 10.1007/978-1-60327-524-8_10 D2 10.1007/978-1-60327-524-8 PG 36 WC Medicine, General & Internal; Surgery; Urology & Nephrology SC General & Internal Medicine; Surgery; Urology & Nephrology GA BOL05 UT WOS:000276922600011 ER PT S AU Wilson, MA Hunt, PR Wolkow, CA AF Wilson, Mark A. Hunt, Piper R. Wolkow, Catherine A. BE Qian, MC Rimando, AM TI Using Caenorhabditis elegans To Study Bioactivities of Natural Products from Small Fruits SO FLAVOR AND HEALTH BENEFITS OF SMALL FRUITS SE ACS Symposium Series LA English DT Proceedings Paper CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc ID LIFE-SPAN; RESVERATROL; ANTIOXIDANT; DIET; CELL AB Natural products from small fruits elicit a variety of bioactivities studied primarily in vitro. Although rigorous, these approaches fail to replicate the inherent complexity of the whole organism, where uptake and detoxification processes limit interactions with the target of interest. Currently, most in vivo studies use rodent models, such as mice and rats. Invertebrates, such as Caenorhabditis elegans nematodes, offer an efficient alternative to rodents. C. elegans nematodes are cheap to maintain, easily cultivated in large numbers and amenable to genetic and cellular studies. This chapter provides a brief introduction to the use of C. elegans for in vivo studies of natural products. In addition, we describe our own use of C. elegans to elucidate bioactivities of blueberry proanthocyanins and a collection of resveratrol analogs, with the goal of encouraging new investigations of natural products using C. elegans. C1 [Wilson, Mark A.; Hunt, Piper R.; Wolkow, Catherine A.] NIA, Neurosci Lab, Intramural Res Program, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Wilson, MA (reprint author), NIA, Neurosci Lab, Intramural Res Program, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM wolkowca@grc.nia.nih.gov RI Hunt, Piper/G-1555-2012 OI Hunt, Piper/0000-0003-0538-7606 NR 30 TC 0 Z9 0 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2549-7 J9 ACS SYM SER JI ACS Symp. Ser. PY 2010 VL 1035 BP 227 EP 238 PG 12 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA BVT24 UT WOS:000292708300014 ER PT B AU Moxey-Mims, M Goodyer, P AF Moxey-Mims, Marva Goodyer, Paul BE Feld, LG Kaskel, FJ TI A Physiologic Approach to Hereditary Tubulopathies SO FLUID AND ELECTROLYTES IN PEDIATRICS: A COMPREHENSIVE HANDBOOK SE Nutrition and Health Series LA English DT Article; Book Chapter DE Fanconi syndrome; cystinosis; salt-losing syndromes; aminoaciduria; bicarbonaturia; proximal tubule; phosphaturia; pseudohypoaldosteronism; nephrogenic diabetes insipidus; Bartter syndrome ID NEPHROGENIC DIABETES-INSIPIDUS; EPITHELIAL SODIUM-CHANNEL; POTASSIUM CONCENTRATION GRADIENT; MINERALOCORTICOID RECEPTOR GENE; CONGENITAL ADRENAL-HYPERPLASIA; PSEUDOHYPOALDOSTERONISM TYPE-1; NEPHROPATHIC CYSTINOSIS; HYPOKALEMIC ALKALOSIS; BARTTERS-SYNDROME; CHILDREN AB 1. The primary function of the proximal tubule is the bulk reabsorption of inorganic and organic solutes. 2. Fanconi syndrome is a generalized term applied to a large number of disorders characterized by defective proximal tubular reabsorption of numerous Solutes. The most common inherited cause is cystinosis. 3. Normally, 99% of filtered sodium is actively reabsorbed by the renal tubules, with sequential fine-tuning as the glomerular filtrate moves along the nephron. 4. Isolated salt-losing syndromes result from luminal transporter disorders along the thick ascending limb of Henle. the distal convoluted tubule, or the cortical collecting tubule. C1 [Moxey-Mims, Marva] NIDDK, Pediat Nephrol Program, NIH, DKUH, Bethesda, MD 20892 USA. [Goodyer, Paul] McGill Univ, Montreal, PQ, Canada. RP Moxey-Mims, M (reprint author), NIDDK, Pediat Nephrol Program, NIH, DKUH, Bethesda, MD 20892 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 978-1-60327-224-7 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 323 EP 339 DI 10.1007/978-1-60327-225-4_15 D2 10.1007/978-1-60327-225-4 PG 17 WC Nutrition & Dietetics; Pediatrics SC Nutrition & Dietetics; Pediatrics GA BMT26 UT WOS:000273523800015 ER PT S AU Meaburn, KJ AF Meaburn, Karen J. BE Bridger, JM Volpi, EV TI Fluorescence In Situ Hybridization on 3D Cultures of Tumor Cells SO FLUORESCENCE IN SITU HYBRIDIZATION (FISH): PROTOCOLS AND APPLICATIONS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE FISH; 3D cell culture; Acini; Interphase; Nuclear architecture; Tissue models; Genome organization; Early tumorigenesis ID BREAST EPITHELIAL-CELLS; CHROMOSOME TERRITORIES; GENOME; ORGANIZATION; ARCHITECTURE; MODELS; DIMENSIONS; ACINI AB Genomes are spatially highly organized within interphase nuclei. Spatial genome organization is increasingly linked to genome function. Fluorescence in situ hybridization (FISH) allows the visualization of specific regions of the genome for spatial mapping. While most gene localization studies have been performed on cultured cells, genome organization is likely to be different in the context of tissues. Three-dimensional (3D) culture model systems provide a powerful tool to study the contribution of tissue organization to gene expression and organization. However, FISH on 3D cultures is technically more challenging than on monocultures. Here, we describe an optimized protocol for interphase DNA FISH on 3D cultures of the breast epithelial cell line MCF-10A.B2, which forms breast acini and can be used as a model for early breast cancer. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Meaburn, KJ (reprint author), NCI, NIH, Bethesda, MD 20892 USA. OI Meaburn, Karen/0000-0002-1327-5957 FU Intramural NIH HHS NR 18 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-788-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 659 BP 323 EP 336 DI 10.1007/978-1-60761-789-1_25 D2 10.1007/978-1-60761-789-1 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BRC22 UT WOS:000282335500025 PM 20809324 ER PT J AU Roy, S Hart, CM AF Roy, Swarnava Hart, Craig M. TI Targeted gene replacement by homologous recombination in Drosophila stimulates production of second-site mutations SO FLY LA English DT Article DE Drosophila; BEAF; insulator; gene targeting; homologous recombination ID BREAK REPAIR; MELANOGASTER; KNOCKOUT; REVEALS AB Gene replacement by homologous recombination is a powerful technique for generating mutations in Drosophila. While using this technique for the BEAF gene, we encountered non-targeted lethal mutations on the target chromosome that complicated the analysis of the BEAF mutations until they were discovered and removed by meiotic recombination. Subsequent experiments indicated that the gene-targeting method leads to a modest but significant three-fold increase in the rate of production of non-targeted lethal mutations. It is important to be aware of this phenomenon when using this method. C1 [Roy, Swarnava] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Hart, Craig M.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. RP Roy, S (reprint author), NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM roys2@niddk.nih.gov RI Hart, Craig/B-4832-2016 OI Hart, Craig/0000-0002-9870-991X FU NSF [0718898]; Louisiana Board of Regents [LEQSF (2004-05)-RD-A-11]; LSU FX We thank Chris Lin for technical assistance and maintaining fly stocks. This work was supported by grants from the NSF (0718898), the Louisiana Board of Regents (LEQSF (2004-05)-RD-A-11) and a LSU Faculty Research Grant. NR 21 TC 3 Z9 3 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1933-6934 J9 FLY JI Fly PD JAN-MAR PY 2010 VL 4 IS 1 BP 12 EP 17 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 572HY UT WOS:000275820100002 PM 20139711 ER PT J AU Lipardi, C Paterson, BM AF Lipardi, Concetta Paterson, Bruce M. TI Identification of an RNA-dependent RNA polymerase in Drosophila establishes a common theme in RNA silencing SO FLY LA English DT Article DE transposon suppression; endo siRNAs; elongator; genome defense; immunity ID C-ELEGANS; ENDOGENOUS SIRNAS; FISSION YEAST; TOMATO LEAVES; INTERFERENCE; AMPLIFICATION; BIOGENESIS; PROTEINS; GENOME; PLANTS AB In lower eukaryotes, such as A. thaliana, C. elegans, S. pombe and N. crassa, RNA-dependent RNA polymerase (RdRP) is a required component of the RNA silencing pathway. Remarkably, even though robust RNA silencing occurs in Drosophila in response to exogenous dsRNA and siRNAs, no RdRP homolog has been identified in the Drosophila genome or in any other higher eukaryote characteristic of the known cellular RdRPs. We showed recently that the largest subunit of the Drosophila RNA polymerase II core elongator complex, called D-elp1, has RdRP activity capable of using unprimed or primed synthesis mechanisms to convert single stranded RNA templates into double stranded RNA (dsRNA) that can be cleaved by Dcr-2. Loss of D-elp1 inhibits both siRNA and dsRNA directed RNAi in S2 cells but does not affect micro RNA targeting. Transposon RNA levels also increase with the loss of D-elp1 while the corresponding endo siRNAs, critical for transposon suppression, are dramatically reduced and this is correlated with a reduction in transposon antisense RNA levels. D-elp1 associates tightly with Dicer-2, similar to the Dicer-RdRP interaction observed in lower eukaryotes. With the exception of S. cerevisiae, which lacks the RNAi machinery altogether, RdRP activity is conserved in the elp1 homologs from S. pombe to human. This commentary focuses on the importance and universality of RdRP in RNA silencing. C1 [Lipardi, Concetta; Paterson, Bruce M.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Paterson, BM (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM patersob@mail.nih.gov NR 35 TC 8 Z9 8 U1 1 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1933-6934 J9 FLY JI Fly PD JAN-MAR PY 2010 VL 4 IS 1 BP 30 EP 35 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 572HY UT WOS:000275820100006 PM 20023402 ER PT J AU Wesolowska, N Rong, YKS AF Wesolowska, Natalia Rong, Yikang S. TI The past, present and future of gene targeting in Drosophila SO FLY LA English DT Review DE gene targeting; Drosophila mutagenesis; SIRT; ends-in; ends-out; recombineering ID ZINC-FINGER NUCLEASES; HOMOLOGOUS RECOMBINATION; ENDS-OUT; MELANOGASTER; DNA; EFFICIENT; TRANSFORMATION; MUTAGENESIS; REPAIR; REPLACEMENT AB The beginnings of Drosophila as a model organism reach far back into the 1900s to Thomas Hunt Morgan's first fly room. The success of this system for the study of genetics is closely linked to the fact that the fly is amenable to complex genetic manipulations so that random mutagenesis screens can be easily performed. Nonetheless, current advances in genomics and in our ability to predict protein function emphasize the importance of mutagenesis methods that are not random, but rather give the researcher control over how the gene is modified. Gene targeting in Drosophila, developed almost a decade ago, makes use of the organism's own DNA repair machinery to exchange genetic information between a chromosomal target and an exogenous template. Here we discuss available targeting methods and recent advances that facilitate repeated targeting and open the doors to routine allelic studies. C1 [Wesolowska, Natalia] Johns Hopkins Univ, JHU NIH Grad Partnership Program, Baltimore, MD 21218 USA. [Rong, Yikang S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wesolowska, N (reprint author), Johns Hopkins Univ, JHU NIH Grad Partnership Program, Baltimore, MD 21218 USA. EM wesolown@mail.nih.gov FU NCI FX We thank Dr. Jean-Claude Walser (University of Basel, Basel, Switzerland) and Nazanin Ashourian at NCI for comments on the manuscript. This work was supported by the NCI Intramural Program. NR 35 TC 11 Z9 12 U1 2 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1933-6934 EI 1933-6942 J9 FLY JI Fly PD JAN-MAR PY 2010 VL 4 IS 1 BP 53 EP 59 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 572HY UT WOS:000275820100010 PM 20139712 ER PT J AU Auerbach, SS Bristol, DW Peckham, JC Travlos, GS Hebert, CD Chhabra, RS AF Auerbach, Scott S. Bristol, Douglas W. Peckham, John C. Travlos, Gregory S. Hebert, Charles D. Chhabra, Rajendra S. TI Toxicity and carcinogenicity studies of methylene blue trihydrate in F344N rats and B6C3F1 mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Methylene blue trihydrate; Methemoglobin; Chronic toxicity; Carcinogenicity ID ZERO-DOSE CONTROL; HIGHLY IONIZED DRUGS; PHARMACOKINETICS; LEUKEMIA; TESTS AB Methylene blue trihydrate has a variety of biomedical and biologically therapeutic applications. Groups of 50 male and 50 female rats and mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose Solution by gavage at doses of 0, 5, 25, or 50 mg/kg bw/day (rats) or 0, 2.5, 12.5, and 25 mg/kg bw/day (mice), 5 days per week for 2 years. In rats survival of all dosed groups was similar to that of the vehicle controls, whereas mice exhibited a dose-dependent increase in survival. Rats receiving 25 and 50 mg/kg bw/day and mice receiving 25 mg/kg bw/day developed mild anemia. The incidences of pancreatic islet cell adenoma and adenoma or carcinoma (combined) were increased in all dosed groups of male rats, but increases were statistically significant in 25 mg/kg bw/day males only and the dose-response was non-linear. There was a corresponding increase in the incidence of pancreatic islet cell hyperplasia but statistically significant only in the 50 mg/kg bw/day male rats. There were no significant increases in neoplastic transformation observed in the mice; however, positive trends were noted for adenoma or carcinoma (combined) of the small intestine and malignant lymphoma. Published by Elsevier Ltd. C1 [Auerbach, Scott S.; Bristol, Douglas W.; Peckham, John C.; Travlos, Gregory S.; Chhabra, Rajendra S.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Hebert, Charles D.] So Res Inst, Birmingham, AL 35205 USA. RP Auerbach, SS (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM auerbachs@niehs.nih.gov; bristol@niehs.nih.gov; peckham@niehs.nih.gov; travlos@niehs.nih.gov; hebert@southernresearch.org; chhabrar@niehs.nih.gov FU NIH; Environmental Health Sciences [1 Z01 ES045004-11 BB] FX We thank Dr. Matthew D. Stout, NIEHS, and Dr. Michelle J. Hooth, NIEHS, for their excellent review of the manuscript. 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 ES045004-11 BB. NR 35 TC 13 Z9 14 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2010 VL 48 IS 1 BP 169 EP 177 DI 10.1016/j.fct.2009.09.034 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 554UJ UT WOS:000274460400028 PM 19804809 ER PT J AU Chang, AHK Levine, RL AF Chang, Allen Hung-Kang Levine, Rodney L. TI Is Lysosome the Non-proteasomal Degradation Pathway for Iron Regulatory Protein 2? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Chang, Allen Hung-Kang; Levine, Rodney L.] NHLBI, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S77 EP S77 DI 10.1016/j.freeradbiomed.2010.10.190 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000207 ER PT J AU Chatterjee, S DaSilva, DG Jiang, LJ Bonini, MG Leinisch, F Kadiiska, M Mason, RP AF Chatterjee, Saurabh DaSilva, Douglas Ganini Jiang, Linjie Bonini, Marcelo G. Leinisch, Fabian Kadiiska, Maria Mason, Ronald P. TI Free Radical Metabolism by Cytochrome P450-2E1 and NADPH Oxidase Activation Forms Protein Radicals and Tyrosine Nitration in Obesity-Associated Non-alcoholic Fatty Liver Disease SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Chatterjee, Saurabh; Jiang, Linjie; Leinisch, Fabian; Kadiiska, Maria; Mason, Ronald P.] NIEHS, Res Triangle Pk, NC USA. [DaSilva, Douglas Ganini] Univ Fed Sao Paulo, UNIFESP, Sao Paulo, Brazil. [Bonini, Marcelo G.] Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S163 EP S164 DI 10.1016/j.freeradbiomed.2010.10.460 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000470 ER PT J AU Chatterjee, S Kadiiska, M Mason, RP AF Chatterjee, Saurabh Kadiiska, Maria Mason, Ronald P. TI P2X7 Receptor-mediated Free Radical Production by Leptin is key to Kupffer cell Activation and MHC Class II Expression in Worsening Steatohepatitis of Obesity SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Chatterjee, Saurabh; Kadiiska, Maria; Mason, Ronald P.] NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S140 EP S141 DI 10.1016/j.freeradbiomed.2010.10.389 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000401 ER PT J AU Ehrenshaft, M Zhao, BZ Andley, UP Mason, RP Roberts, JE AF Ehrenshaft, Marilyn Zhao, Baozhang Andley, Usha P. Mason, Ronald P. Roberts, Joan E. TI Immunological Detection of NFK in Photo-oxidized Lens Alpha-crystallin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Ehrenshaft, Marilyn; Zhao, Baozhang; Mason, Ronald P.] NIEHS, NIH, Res Triangle Pk, NC USA. [Andley, Usha P.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Roberts, Joan E.] Fordham Univ, Bronx, NY 10458 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S164 EP S165 DI 10.1016/j.freeradbiomed.2010.10.463 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000473 ER PT J AU Enika, N Viachaslau, BM Mohanty, JG Nyhan, D Berkowitz, DE Strouse, JJ Rifkind, JM AF Enika, Nagababu Viachaslau, Barodka M. Mohanty, Joy G. Nyhan, Daniel Berkowitz, Dan E. Strouse, John J. Rifkind, Joseph M. TI Increased Heme Degradation and Impaired Deformability of Red Blood Cells in Sickle Cell Disease and Anemia SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Enika, Nagababu; Mohanty, Joy G.; Rifkind, Joseph M.] NIA, Bethesda, MD 20892 USA. [Viachaslau, Barodka M.; Nyhan, Daniel; Berkowitz, Dan E.; Strouse, John J.] Johns Hopkins Med Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S165 EP S165 DI 10.1016/j.freeradbiomed.2010.10.464 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000474 ER PT J AU Enika, N Rifkind, JM AF Enika, Nagababu Rifkind, Joseph M. TI S-nitrosothiols Formation during the Reductive Nitrosylation of Methemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Enika, Nagababu; Rifkind, Joseph M.] NIA, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S114 EP S114 DI 10.1016/j.freeradbiomed.2010.10.306 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000320 ER PT J AU Finkel, T AF Finkel, Toren TI MITOCHONDRIAL AND REDOX REGULATION OF STEM CELL BIOLOGY SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Finkel, Toren] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S5 EP S5 DI 10.1016/j.freeradbiomed.2010.10.672 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000009 ER PT J AU Kadiiska, M AF Kadiiska, Maria TI Validation of Best Detection Methods for Measuring Oxidative Stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Kadiiska, Maria] NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S166 EP S167 DI 10.1016/j.freeradbiomed.2010.10.471 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000480 ER PT J AU Leinisch, F Ranguelova, K Jiang, JJ Sinha, BK Corbett, J Mason, RP AF Leinisch, Fabian Ranguelova, Kalina Jiang, JinJie Sinha, Birandra K. Corbett, Jean Mason, Ronald P. TI The Assessment of Artifacts Originating from the Non-Radical Forrester-Hepburn Mechanism as a Side Reaction in Sulfite Radical Spin Trapping by DMPO and its N-15 Analog SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Leinisch, Fabian; Ranguelova, Kalina; Jiang, JinJie; Sinha, Birandra K.; Corbett, Jean; Mason, Ronald P.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S211 EP S212 DI 10.1016/j.freeradbiomed.2010.10.616 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000624 ER PT J AU Matsumoto, K Nakanishi, I Krishna, MC AF Matsumoto, Ken-ichiro Nakanishi, Ikuo Krishna, Murali C. TI Reaction of Nitroxyl Radicals and GSH; pH Dependence SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Matsumoto, Ken-ichiro; Nakanishi, Ikuo] NCI, Bethesda, MD USA. [Krishna, Murali C.] Natl Inst Radiol Sci, Bethesda, MD USA. RI Nakanishi, Ikuo/E-4430-2012 OI Nakanishi, Ikuo/0000-0001-9204-0664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S212 EP S212 DI 10.1016/j.freeradbiomed.2010.10.619 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000627 ER PT J AU Mattmiller, S Carlson, B Corl, C Sordillo, L AF Mattmiller, Sarah Carlson, Bradley Corl, Chris Sordillo, Lorraine TI Selenoenzyme Status Affects Eicosanoid Biosynthesis in Macrophages SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Mattmiller, Sarah; Corl, Chris; Sordillo, Lorraine] Michigan State Univ, E Lansing, MI 48824 USA. [Carlson, Bradley] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S145 EP S146 DI 10.1016/j.freeradbiomed.2010.10.407 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000419 ER PT J AU Merker, MP Bongard, RD Lindemer, BJ Baumgardt, S Gonzalez, FI AF Merker, Marilyn P. Bongard, Robert D. Lindemer, Brian J. Baumgardt, Shelley Gonzalez, Frank I. TI Impact of NAD(P)H:quinone Oxidoreductase 1 (NQ01) on Quinone Reduction During Passage Through the Mouse Pulmonary Circulation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Merker, Marilyn P.; Bongard, Robert D.; Lindemer, Brian J.; Baumgardt, Shelley] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Merker, Marilyn P.] Zablocki VAMC, Milwaukee, WI 53295 USA. [Gonzalez, Frank I.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S178 EP S178 DI 10.1016/j.freeradbiomed.2010.10.505 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000514 ER PT J AU Park, JW Piknova, B Schechter, AN AF Park, Ji Won Piknova, Barbora Schechter, Alan N. TI Effect of Storage on Levels of Nitric Oxide Metabolites in Platelet Preparation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Park, Ji Won; Piknova, Barbora; Schechter, Alan N.] NIDDK NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S118 EP S118 DI 10.1016/j.freeradbiomed.2010.10.321 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000335 ER PT J AU Piknova, B Kocharyan, A Silva, A Schechter, AN AF Piknova, Barbora Kocharyan, Ara Silva, Afonso Schechter, Alan N. TI Role of Nitrite in Neurovascular Coupling: Possible Nitric Oxide-related and -independent Mechanisms SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Piknova, Barbora; Schechter, Alan N.] NIH NIDDK, Bethesda, MD 20892 USA. [Kocharyan, Ara; Silva, Afonso] NIH NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S118 EP S118 DI 10.1016/j.freeradbiomed.2010.10.322 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000336 ER PT J AU Polzella, BJ Piknova, B Pluta, R Schechter, AN AF Polzella, Benjamin J. Piknova, Barbora Pluta, Rzyszard Schechter, Alan N. TI Nitric Oxide Metabolite Levels as a Function of Blood Oxygenation: An in vivo Animal Study SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Polzella, Benjamin J.; Piknova, Barbora; Schechter, Alan N.] NIDDK, Bethesda, MD 20892 USA. [Pluta, Rzyszard] NINCDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S119 EP S119 DI 10.1016/j.freeradbiomed.2010.10.325 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000339 ER PT J AU Ranguelova, K Garantziotis, S Rice, AB Mason, RP AF Ranguelova, Kalina Garantziotis, Stavros Rice, Annette B. Mason, Ronald P. TI Formation of Highly Reactive Sulfite-Derived Free Radicals by the Activation of Human Neutrophils SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Ranguelova, Kalina; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Garantziotis, Stavros; Rice, Annette B.] NIEHS, Climat Res Unit, NIH, Res Triangle Pk, NC 27709 USA. RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S214 EP S214 DI 10.1016/j.freeradbiomed.2010.10.625 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000633 ER PT J AU Ruggiero, C Ehrenshaft, M Stadler, K AF Ruggiero, Christine Ehrenshaft, Marilyn Stadler, Krisztian TI Early Oxidative Stress Precedes the Derailment of Mitochondrial Bioenergetics in the Prediabetic Kidney SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Ehrenshaft, Marilyn] NIEHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S42 EP S42 DI 10.1016/j.freeradbiomed.2010.10.088 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000108 ER PT J AU Salmon, A Styskal, J Musi, N Levine, R Richardson, A AF Salmon, Adam Styskal, JennaLynn Musi, Nicolas Levine, Rodney Richardson, Arlan TI Obesity-induced Insulin Resistance is Regulated by Methionine Sulfoxide Reductase SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Salmon, Adam; Styskal, JennaLynn; Musi, Nicolas; Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Musi, Nicolas; Richardson, Arlan] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Levine, Rodney] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S41 EP S41 DI 10.1016/j.freeradbiomed.2010.10.085 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000105 ER PT J AU Sarsour, EH Kalen, AL Xiao, Z Chaudhuri, L Veenstra, TD Goswami, PC AF Sarsour, Ehab H. Kalen, Amanada L. Xiao, Zhen Chaudhuri, Leena Veenstra, Timothy D. Goswami, Prabhat C. TI An Inverse Correlation Between Manganese Superoxide Dismutase Activity and Glucose Consumption: MnSOD, a New Molecular Player for the Warburg Effect SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Sarsour, Ehab H.; Kalen, Amanada L.; Chaudhuri, Leena; Goswami, Prabhat C.] Univ Iowa, Iowa City, IA 52242 USA. [Xiao, Zhen; Veenstra, Timothy D.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S69 EP S69 DI 10.1016/j.freeradbiomed.2010.10.169 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000187 ER PT J AU Scarbrough, PM Mattson, D Gius, D Watson, WH Spitz, DR AF Scarbrough, Peter M. Mattson, David Gius, David Watson, Walter H. Spitz, Douglas R. TI Inhibitors of Glucose and Hydroperoxide Metabolism Potentiate 17-AAG-induced Cancer Cell Killing via Oxidative Stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Scarbrough, Peter M.; Spitz, Douglas R.] Univ Iowa, Iowa City, IA 52242 USA. [Mattson, David] Roswell Pk Canc Inst, Buffalo, NY USA. [Gius, David] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Gius, David] NCI, Bethesda, MD 20892 USA. [Watson, Walter H.] Univ Louisville, Louisville, KY 40292 USA. [Watson, Walter H.] Johns Hopkins Bloomberg Sch Publ Hlth, Bloomsburg, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S69 EP S69 DI 10.1016/j.freeradbiomed.2010.10.170 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000188 ER PT J AU Summers, FA Mason, RP Bonini, MG AF Summers, Fiona A. Mason, Ronald P. Bonini, Marcelo G. TI A Novel Peroxidase Activity of Human Manganese Superoxide Dismutase SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Summers, Fiona A.; Mason, Ronald P.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Bonini, Marcelo G.] Univ Illinois, Chicago, IL 60680 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S103 EP S103 DI 10.1016/j.freeradbiomed.2010.10.273 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000288 ER PT J AU Tanaka, M Han, S Kupfer, PA Leumann, CJ Chock, B Sonntag, WE AF Tanaka, Mikiei Han, Song Kupfer, Pascal A. Leumann, Christian J. Chock, Boon Sonntag, William E. TI Identification of Selectively Damaged mRNA in Response to Oxidative Stress: Characterization of Abasic sites using an Aldehyde Reactive Probe SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Tanaka, Mikiei; Han, Song; Sonntag, William E.] Oklahoma Univ HSC, Oklahoma City, OK USA. [Kupfer, Pascal A.; Leumann, Christian J.] Univ Bern, CH-3012 Bern, Switzerland. [Chock, Boon] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S172 EP S172 DI 10.1016/j.freeradbiomed.2010.10.490 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000500 ER PT J AU Tiso, M Tejero, J Basu, S Azarov, I Wang, XD Simplaceanu, V Frizzell, S Jayaraman, T Geary, L Shapiro, C Ho, CE Shiva, S Kim-Shapiro, DB Gladwin, MT AF Tiso, Mauro Tejero, Jesus Basu, Swati Azarov, Ivan Wang, Xunde Simplaceanu, Virgil Frizzell, Sheila Jayaraman, Thottala Geary, Lisa Shapiro, Calli Ho, Chien Shiva, Sruti Kim-Shapiro, Daniel B. Gladwin, Mark T. TI Heme Coordination and Nitrite Reductase Activity of Human Neuroglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Tiso, Mauro; Tejero, Jesus; Frizzell, Sheila; Jayaraman, Thottala; Geary, Lisa; Shapiro, Calli; Shiva, Sruti; Gladwin, Mark T.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Basu, Swati; Azarov, Ivan; Kim-Shapiro, Daniel B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Wang, Xunde] NHLBI, NIH, Bethesda, MD 20892 USA. [Simplaceanu, Virgil; Ho, Chien] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. RI Ho, Chien/O-6112-2016; OI Ho, Chien/0000-0002-4094-9232; Tejero, Jesus/0000-0003-3245-9978 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S121 EP S121 DI 10.1016/j.freeradbiomed.2010.10.331 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000345 ER PT J AU Zhao, BZ Ranguelova, K Jiang, JJ Zielonka, J Kalyanaraman, B Ronald, MP AF Zhao, Baozhong Ranguelova, Kalina Jiang, JinJie Zielonka, Jacek Kalyanaraman, Balaraman Ronald, Mason P. TI Studies on the Photosensitized Reduction of Resorufin and Implications for the Detection of Oxidative Stress with Amplex Red SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 17th Annual Meeting of the Society-for-Free-Radical-Biology-Medicine /15th Biennial Meeting of the Society-for-Free-Radical-Research-International CY NOV 17-21, 2010 CL Orlando, FL SP Soc Free Radi Biol Med, Soc Free Radi Res Int C1 [Zhao, Baozhong; Ranguelova, Kalina; Jiang, JinJie; Ronald, Mason P.] NIEHS, NIH, Res Triangle Pk, NC USA. [Zielonka, Jacek; Kalyanaraman, Balaraman] Med Coll Wisconsin, Milwaukee, WI USA. RI Zielonka, Jacek/N-9546-2014 OI Zielonka, Jacek/0000-0002-2524-0145 NR 0 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2010 VL 49 SU 1 BP S105 EP S106 DI 10.1016/j.freeradbiomed.2010.10.280 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 681VD UT WOS:000284348000295 ER PT S AU Hyodo, F Matsumoto, S Hyodo, E Matsumoto, A Matsumoto, K Krishna, MC AF Hyodo, F. Matsumoto, S. Hyodo, E. Matsumoto, A. Matsumoto, K. Krishna, M. C. BE Uppu, RM Murthy, SN Pryor, WA Parinandi, NL TI In Vivo Measurement of Tissue Oxygen Using Electron Paramagnetic Resonance Spectroscopy with Oxygen-Sensitive Paramagnetic Particle, Lithium Phthalocyanine SO FREE RADICALS AND ANTIOXIDANT PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Lithium phthalocyanine (LiPc); oxymetry; in vivo tissue oxygen; tumor; EPR ID TUMOR OXYGENATION; CONTINUOUS-WAVE; INDIA INK; EPR; OXIMETRY; PROBE; HYPOXIA AB The partial pressure of oxygen (pO(2)) plays a determining role in the energy metabolism of aerobic cells. However, low pO(2) level induces pathophysiological conditions such as tumor hypoxia, ischemia or reperfusion injury, and delayed/altered wound healing. Especially, pO(2) level in the tumor is known to be related to tumor progression and effectiveness of radiotherapy. To monitor the pO(2) levels ill Vivo, continuous wave (CW) and time-domain (TD) electron paramagnetic resonance (EPR) spectroscopy method was used, in Which Surface coil resonator and Lithium phthalocyanine (LiPc) as oxygen sensor were crucial. Once LiPc particles are embedded in a desired location of organ/tissue, the pO(2) level call be monitored repeatedly and non-invasively. This method is based oil the effect of oxygen concentration oil the EPR spectra of LiPc which offers several advantages as follows: (I) high sensitivity, (2) minimum invasiveness, (3) repeated measurements, (4) absence of toxicity (non-toxic), and (5) measurement in a local region of the tissue With embedded LiPc. Therefore, in this chapter, we describe the method using CW and TD EPR spectroscopy with oxygen-sensitive particle, LiPc, for in vivo monitoring of oxygen. C1 [Hyodo, F.; Matsumoto, S.; Matsumoto, A.; Matsumoto, K.; Krishna, M. C.] NCI, Biophys Spect Sect, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hyodo, F (reprint author), NCI, Biophys Spect Sect, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 19 TC 2 Z9 3 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 978-1-58829-710-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 610 SI 2nd BP 29 EP 39 DI 10.1007/978-1-60327-029-8_2 D2 10.1007/978-1-60327-029-8 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BND73 UT WOS:000274239900002 PM 20013170 ER PT S AU Nagababu, E Rifkind, JM AF Nagababu, Enika Rifkind, Joseph M. BE Uppu, RM Murthy, SN Pryor, WA Parinandi, NL TI Measurement of Plasma Nitrite by Chemiluminescence SO FREE RADICALS AND ANTIOXIDANT PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Plasma; nitrite; nitric oxide; endothelial nitric oxide synthase; chemiluminescence; ascorbic acid ID OXIDE SYNTHASE ACTIVITY; S-NITROSOTHIOLS; N-NITROSO; REDUCTION; DEOXYHEMOGLOBIN; TISSUES; NITRATE; FLUIDS AB Studies have demonstrated that plasma nitrite (NO2-) reflects endothelial nitric oxide (NO) production. In addition, NO2- has been shown to have biological activities associated with its reduction to NO in blood and tissues. Therefore, determination of plasma NO2- has been proposed as a prognostic market for cardiovascular diseases. Typical concentrations of NO2- in the plasma arc in the nanomolar range and determination of this NO2- poses a challenge in terms of both sensitivity and specificity. Thus, a highly sensitive, chemiluminescence method that is based on the reduction of NO2- by potassium iodide and iodine is being used to determine the nitrite in biological fluids. This method has the sensitivity, but also measures other nitric oxide Species Such as S-nitrosothiols and N-nitrosamines. We, therefore, developed an alternative method based on the reduction of NO2- by ascorbic acid in strongly acidic media. As part of the methodology, glacial acetic acid and ascorbic acid are introduced into the purge vessel of the NO analyzer. Samples containing NO2- are injected into the purge vessel and the chemiluminescence signals generated as a result of the formation of NO are then measured. We find that under these conditions NO2- is stoichiometrically reduced to NO. Other traditional NO-generating species, Such as S-nitrosothiols, N-nitrosamines, nitrated lipids, and nitrated proteins, did not interfere in the determination of plasma NO2- Using the present method, plasma NO2- in fasting human Subjects has been determined to be in the range of 56-210 nM (mean +/- SD = 110 +/- 36 nM; n = 8). C1 [Nagababu, Enika; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP Nagababu, E (reprint author), NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. FU Intramural NIH HHS [ZIA AG000433-04] NR 19 TC 17 Z9 18 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-710-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 610 SI 2nd BP 41 EP 49 DI 10.1007/978-1-60327-029-8_3 D2 10.1007/978-1-60327-029-8 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BND73 UT WOS:000274239900003 PM 20013171 ER PT S AU Nagababu, E Rifkind, JM Boindala, S Nakka, L AF Nagababu, Enika Rifkind, Joseph M. Boindala, Sesikeran Nakka, Lakshmaiah BE Uppu, RM Murthy, SN Pryor, WA Parinandi, NL TI Assessment of Antioxidant Activity of Eugenol In Vitro and In Vivo SO FREE RADICALS AND ANTIOXIDANT PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Reactive oxygen species; antioxidants; eugenol; lipid peroxidation; TBARS; carbon tetrachloride hepatotoxicity ID RAT-LIVER MITOCHONDRIA; LIPID-PEROXIDATION; FREE-RADICALS; HEPATOTOXICITY; ASCORBATE; TOXICITY; METALS AB Reactive oxygen species arc implicated in many human diseases and aging process. Much of the evidence is based oil experimental data indicating increasing rates of lipid peroxidation in disease states and the ameliorating effects of antioxidants. It is becoming increasingly evident that the natural antioxidants, which have phenolic structure, play an important role in protecting the tissues against free radical damage. Eugenol (4-allyl-2 methoxyphenol) is one such naturally occurring phenolic compound. The antioxidant activity of eugenol was evaluated by the extent of protection offered against free radical-mediated lipid peroxidation using both in vitro and in vivo Studies. The in vitro lipid peroxidation was induced in mitochondria by (Fe(II)-ascorbate) or (Fe(II) + H2O2). The lipid peroxidation was assessed colorimetrically by measuring the formation of thiobarbituric acid reactive Substances (TBARS) following the reaction of oxidized lipids with TBA. Eugenol completely inhibited both iron and Fenton reagent-mediated lipid peroxidation. The inhibitory activity of eugenol was about fivefold higher than that observed for alpha-tocopherol and about tenfold less than that observed for BHT. The in vivo lipid peroxidation-mediated liver damage was induced by administration of CCl4 to rats. Eugenol significantly inhibited the rise in SGOT activity and cell necrosis Without protecting the endoplasmic reticulum (ER) damage as assessed by its failure to prevent a decrease in cytochrome p450 and G-6-phosphatase activity. The protective action of eugenol has been found to be due to interception of secondary radicals derived from ER lipids rather than interfering with primary radicals of CCl4(center dot CCl3/CCl3OO center dot). C1 [Nagababu, Enika; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. [Boindala, Sesikeran; Nakka, Lakshmaiah] Jamai Osmania, Indian Council Med Res, Natl Inst Nutr, Hyderabad, Andhra Pradesh, India. RP Nagababu, E (reprint author), NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. NR 27 TC 26 Z9 27 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-710-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 610 SI 2nd BP 165 EP 180 DI 10.1007/978-1-60327-029-8_10 D2 10.1007/978-1-60327-029-8 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BND73 UT WOS:000274239900010 PM 20013178 ER PT J AU Kiyatkin, EA AF Kiyatkin, Eugene A. TI Brain temperature homeostasis: physiological fluctuations and pathological shifts SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Metabolism; Cerebral blood flow; Brain temperature; Hyperthermia; Hypothermia; Metabolic brain activation; Arousal; Behavior; Psychomotor stimulants; Neural injury; Blood-brain barrier; Neurotoxicity; Review ID CENTRAL-NERVOUS-SYSTEM; CEREBRAL-BLOOD-FLOW; METHAMPHETAMINE-INDUCED HYPERTHERMIA; PREOPTIC-ANTERIOR HYPOTHALAMUS; LOCALIZED THERMAL-CHANGES; NORMOTENSIVE YOUNG-RATS; IN-VITRO; PROLONGED EXERCISE; UNRESTRAINED RATS; HEAT-STRESS AB Brain temperature is a physiological parameter, reflecting the balance between metabolism-related intra-brain heat production and heat loss by cerebral circulation to the rest of the body and then to the external environment. First, we present data on brain temperature fluctuations occurring under physiological and behavioral conditions and discuss their mechanisms. Since most processes governing neural activity are temperature-dependent, we consider how naturally occurring temperature fluctuations could affect neural activity and neural functions. We also consider psychomotor stimulants and show that their hyperthermic effects are state-dependent and modulated by environmental conditions. Since high temperature could irreversibly damage neural cells and worsen various pathological processes, we consider the situations associated with pathological brain hyperthermia and evaluate its role in acute perturbations of brain functions, neurotoxicity, and neurodegeneration. We also discuss the limitations in consideration of brain temperature within the frameworks of physiological regulation and homeostasis. While different adaptive mechanisms could, within some limits, compensate for altered intra-brain heat balance, these mechanisms could fail in real-life situations, resulting in life-threatening health complications. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@mail.nih.gov FU NIH, NIDA FX This work was supported by the Intramural Research Program of the NIH, NIDA. Data described in this review were obtained in collaboration with Dr. Hari S. Sharma, P. Leon Brown, Robert Mitchum, David Bae, and Michael S. Smirnov, whose valuable contribution is greatly appreciated. I wish to thank Michael S. Smirnov and Mary Pfeiffer for editorial assistance, and Dr. Clark Blatteis for comments and suggestions made on the early variant of this review. NR 154 TC 56 Z9 57 U1 2 U2 14 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN 1 PY 2010 VL 15 BP 73 EP 92 DI 10.2741/3608 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 660DN UT WOS:000282619800008 PM 20036808 ER PT J AU Mishra, PK Singh, SR Joshua, IG Tyagi, SC AF Mishra, Paras Kumar Singh, Shree Ram Joshua, Irving G. Tyagi, Suresh C. TI Stem cells as a therapeutic target for diabetes SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Diabetes mellitus; Mesenchymal stem cells; adult stem cells; insulin producing cells; induced pluripotent stem cells; human embryonic stem cells; nuclear reprogramming; MicroRNAs; stem cell therapy; pancreas development; beta-cells regeneration; Review ID INSULIN-PRODUCING CELLS; PANCREATIC BETA-CELLS; UMBILICAL-CORD BLOOD; VERTEBRATE ENDODERM DEVELOPMENT; TO-MESENCHYMAL TRANSITION; IN-VITRO DIFFERENTIATION; ADULT-MOUSE PANCREAS; ISLET-LIKE CLUSTERS; MURINE BONE-MARROW; MALPIGHIAN TUBULES AB The rapidly increasing number of diabetes patients across the world poses a great challenge to the current therapeutic approach. The traditional method of exogenous supply of insulin has ephemeral effect and often causes lethal hypoglycemia that demands to develop a novel strategy. Recent investigations on regeneration of insulin producing cells (IPCs) revealed that in addition to primary source i.e., pancreatic beta cells, IPCs can be derived from several alternative sources including embryonic, adult, mesenchymal and hematopoietic stem cells via the process of proliferation, dedifferentiation, neogenesis, nuclear reprogramming and transdifferentiation. There is considerable success in insulin independency of diabetes patient after transplantation of whole pancreas and / or the islet cells. However, the major challenge for regenerative therapy is to obtain a large source of islet / beta cells donor. Recent advances in the directed differentiation of stem cells generated a promising hope for a better and permanent insulin independency for diabetes. In this review we discussed stem cells as a potential future therapeutic target for the treatment of diabetes and associated diseases. C1 [Tyagi, Suresh C.] Univ Louisville, Sch Med, Dept Physiol & Biophys, Louisville, KY 40202 USA. [Singh, Shree Ram] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Tyagi, SC (reprint author), Univ Louisville, Sch Med, Dept Physiol & Biophys, A-1215,500 S Preston St, Louisville, KY 40202 USA. EM suresh.tyagi@louisville.edu RI Mishra, Paras /B-4760-2010; Singh, Shree Ram/B-7614-2008; OI Singh, Shree Ram/0000-0001-6545-583X; Mishra, Paras Kumar/0000-0002-7810-9239 FU NIH [HL-71010, HL-74185, HL-88012, NS-51568] FX Paras Kumar Mishra, Shree Ram Singh contributed equally to this work. This work was supported in part by the NIH grants HL-71010, HL-74185, HL-88012 and NS-51568. We would like to thank Lindsey Draper and Avinash S. Yadav for their help during preparation of the manuscript. NR 174 TC 18 Z9 19 U1 0 U2 18 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2010 VL 15 BP 461 EP 477 DI 10.2741/3630 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 660DO UT WOS:000282619900004 PM 20036830 ER PT S AU Muller, CE Ferre, S AF Mueller, Christa E. Ferre, Sergi BE AttaUrRahman, FRS Choudhary, MI TI Blocking Striatal Adenosine A2A Receptors: A New Strategy for Basal Ganglia Disorders SO FRONTIERS IN CNS DRUG DISCOVERY, VOL 1 SE Frontiers in CNS Drug Discovery LA English DT Article; Book Chapter DE Adenosine; xanthines; adenine derivative; adenine analog; Parkinson's disease; adenosine receptor; antagonist; istradefylline; A2A receptor; pha lacophore model ID MONOAMINE-OXIDASE-B; C-FOS EXPRESSION; BEARING POLAR SUBSTITUENTS; ANTAGONIST MSX-3 REVERSES; EMISSION-TOMOGRAPHY PET; CENTRAL-NERVOUS-SYSTEM; HIGHER-ORDER OLIGOMERS; MPTP-TREATED MONKEYS; A(2A) RECEPTOR; PARKINSONS-DISEASE AB Adenosine A2A receptors are highly concentrated in the striatum, where they play an important modulatory role of glutamatergic transmission to the GABAergic enkephalinergic neuron, whose function is particularly compromised in Parkinson's disease and in the early stages of Huntington's disease. An important amount of preclinical data suggested the possible application of A2A receptor antagonists in Parkinson's disease, particularly as adjuvant therapy to the currently used dopaminergic agonists. Several A2A receptor antagonists are currently in clinical trials in patients with Parkinson's disease and initial results have been promising. In recent years, many pharmaceutical companies have started programs to develop A2A antagonists for Parkinson's disease and for other indications, such as neurodegenerative diseases in general, depression, and restless legs syndrome. Antagonists with high A2A receptor affinity and selectivity have been developed from various chemical classes of compounds, including xanthines, adenines and other amino -substituted heterocyclic compounds. Novel structures include benzothiazole and thiazolopyridine derivatives. The present review describes properties of standard A2A receptor antagonists including those in clinical development. Furthermore, the different chemical classes of A2A receptor antagonists that have been described in the literature, including recent patent literature, will be presented. C1 [Mueller, Christa E.] Univ Bonn, PharmaCtr Bonn, Inst Pharmaceut, Pharmaceut Chem 1, Bonn, Germany. [Ferre, Sergi] NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. RP Ferre, S (reprint author), NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. EM sferre@intra.nida.nih.gov NR 224 TC 3 Z9 3 U1 2 U2 2 PU BENTHAM SCIENCE PUBL PI BUSUM PA PO BOX 294, BUSUM, 1400 AG, NETHERLANDS SN 1879-6613 BN 978-1-60805-159-5; 978-1-60805-363-6 J9 FRONT CNS DRUG DISC PY 2010 VL 1 BP 304 EP 341 DI 10.2174/978160805159511001010304 PG 38 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA BE2XD UT WOS:000370170000016 ER PT B AU Whitehead, SS Durbin, AP AF Whitehead, Stephen S. Durbin, Anna P. BE Hanley, KA Weaver, SC TI Prospects and Challenges for Dengue Virus Vaccine Development SO FRONTIERS IN DENGUE VIRUS RESEARCH LA English DT Article; Book Chapter ID NEUTRALIZING ANTIBODY-RESPONSE; TERMINALLY TRUNCATED DENGUE-2; TETRAVALENT DNA VACCINE; RHESUS LUNG-CELLS; ATTENUATED DENGUE; ENVELOPE GLYCOPROTEIN; PROTECTIVE EFFICACY; TYPE-2 VIRUS; IMMUNE-RESPONSES; INSECT CELLS AB A safe and effective vaccine for the control of dengue virus disease is urgently needed and long overdue. Because each of the four dengue virus serotypes can cause the full spectrum of dengue disease, vaccination must protect against each serotype. An unprecedented number of vaccine candidates are in development and under clinical evaluation, with live attenuated vaccines being the most advanced. Considerable effort is also being made in the development of inactivated, subunit protein, virus vectored, and DNA vaccine candidates. The need to elicit protective immunity without predisposing for antibody-mediated enhanced disease, the need for rapid and tetravalent protection, and the need for an economical vaccine have presented challenges in the development pathway. Nevertheless, innovative research and development continues to provide solutions to these obstacles. C1 [Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Durbin, Anna P.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD USA. RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM swhitehead@niaid.nih.gov; adurbin@jhsph.edu NR 121 TC 6 Z9 6 U1 1 U2 3 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-50-9 PY 2010 BP 221 EP 237 PG 17 WC Tropical Medicine SC Tropical Medicine GA BLU71 UT WOS:000271100500012 ER PT B AU Goncalvez, AP Purcell, RH Lai, CJ AF Goncalvez, Ana P. Purcell, Robert H. Lai, Ching-Juh BE Hanley, KA Weaver, SC TI Progress in Passive Immunotherapy SO FRONTIERS IN DENGUE VIRUS RESEARCH LA English DT Article; Book Chapter ID WEST-NILE-VIRUS; JAPANESE ENCEPHALITIS-VIRUS; NONSTRUCTURAL PROTEIN NS1; YELLOW-FEVER VIRUS; DENGUE HEMORRHAGIC-FEVER; RESPIRATORY SYNCYTIAL VIRUS; HUMAN MONOCLONAL-ANTIBODIES; MEMORY B-CELLS; FLAVIVIRUS ENVELOPE PROTEIN; INTRAVENOUS IMMUNOGLOBULIN THERAPY AB Dengue is currently endemic in more than one hundred countries around the world. It causes approximately 50-100 million infections annually, including 250,000-500,000 cases of dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). According to the World Health Organization (WHO), two-fifths of the world population is at risk of dengue virus (DENV) infection. It has been suggested that globalization and climate change have had a significant impact on the emergence of DENV in new areas. No vaccine or therapy against DENV is currently approved for use in humans, and alternative strategies to control DENV infection are urgently needed, particularly because the design of such strategies may also inform efforts in vaccine design. This chapter outlines the prophylaxis/therapeutic potential of monoclonal antibodies (MAbs) against DENV and highlights the challenges to implementation of this strategy, including antibody-dependent enhancement (ADE), genetic variability of DENV strains, potential for selection of MAb escape variants, and financial cost. Moreover, we describe recent immunologic and structural studies that have provided a new understanding of antibody-mediated neutralization mechanisms and protection against DENV and other flavivirus infections. These insights are having an important impact on the development of vaccines and antibody-based therapies. C1 [Goncalvez, Ana P.; Lai, Ching-Juh] NIAID, Mol Viral Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Goncalvez, Ana P.; Purcell, Robert H.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Goncalvez, AP (reprint author), NIAID, Mol Viral Biol Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM agoncalvez@niaid.nih.gov; rpurcell@niaid.nih.gov; clai@niaid.nih.gov NR 253 TC 1 Z9 1 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-50-9 PY 2010 BP 265 EP 297 PG 33 WC Tropical Medicine SC Tropical Medicine GA BLU71 UT WOS:000271100500014 ER PT J AU Chong, A Celli, J AF Chong, Audrey Celli, Jean TI The Francisella intracellular life cycle: toward molecular mechanisms of intracellular survival and proliferation SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE Francisella; macrophage; phagosome; pathogenesis AB The tularemia-causing bacterium Francisella tularensis is a facultative intracellular organism with a complex intracellular lifecycle that ensures its survival and proliferation in a variety of mammalian cell types, including professional phagocytes. Because this cycle is essential to Francisella pathogenesis and virulence, much research has focused on deciphering the mechanisms of its intracellular survival and replication and characterizing both bacterial and host determinants of the bacterium's intracellular cycle. Studies of various strains and host cell models have led to the consensual paradigm of Francisella as a cytosolic pathogen, but also to some controversy about its intracellular cycle. In this review, we will detail major findings that have advanced our knowledge of Francisella intracellular survival strategies and also attempt to reconcile discrepancies that exist in our molecular understanding of the Francisella-phagocyte interactions. C1 [Chong, Audrey; Celli, Jean] NIAID, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Celli, J (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, 903 South 4th St, Hamilton, MT 59840 USA. EM jcelli@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy, and Infectious Diseases FX We wish to thank Leigh Knodler for critical reading of the manuscript and Anita Mora for assistance with visual arts. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy, and Infectious Diseases. NR 91 TC 34 Z9 34 U1 2 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2010 VL 1 AR 138 DI 10.3389/fmicb.2010.00138 PG 12 WC Microbiology SC Microbiology GA V31DD UT WOS:000208863400037 PM 21687806 ER PT J AU Tsunetsugu-Yokota, Y Yamamoto, T AF Tsunetsugu-Yokota, Yasuko Yamamoto, Takuya TI Mammalian microRNAs: post-transcriptional gene regulation in RNA virus infection and therapeutic applications SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE mammalian microRNAs; RNA virus infection; host-virus interaction; gene therapy AB RNA silencing mediated by microRNAs (miRNAs) is a recently discovered gene regulatory mechanism involved in various aspects of biology, such as development, cell differentiation and proliferation, and innate immunity against viral infections. miRNAs, which are a class of small (21-25 nucleotides) RNAs, target messenger RNA (mRNA) through incomplete base-pairing with their target sequences resulting in mRNA degradation or translational repression. Although studies of miRNAs have led to numerous sensational discoveries in biology, many fundamental questions about their expression and function still remain. In this review, we discuss the dynamics of the mammalian miRNA machinery and the biological function of miRNAs, focusing on RNA viruses and the various therapeutic applications of miRNAs against viral infections. C1 [Tsunetsugu-Yokota, Yasuko] Natl Inst Infect Dis, Dept Immunol, Tokyo 1628640, Japan. [Yamamoto, Takuya] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Tsunetsugu-Yokota, Y (reprint author), Natl Inst Infect Dis, Dept Immunol, Shinjuku Ku, 1-23-1 Toyama, Tokyo 1628640, Japan. EM yyokota@nih.go.jp RI Yamamoto, Takuya/L-2642-2013 OI Yamamoto, Takuya/0000-0003-3753-1211 FU Ministry of Health, Labor and Welfare of Japan; Health Science Foundation of Japan FX We thank our colleagues in the first laboratory, Department of Immunology, NIID, Japan, for their help and discussion. This paper was supported by grants from the Ministry of Health, Labor and Welfare of Japan and from the Health Science Foundation of Japan. NR 71 TC 5 Z9 5 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2010 VL 1 AR 108 DI 10.3389/fmicb.2010.00108 PG 9 WC Microbiology SC Microbiology GA V31DD UT WOS:000208863400008 PM 21607080 ER PT J AU von Leupoldt, A Bradley, MM Lang, PJ Davenport, PW AF von Leupoldt, Andreas Bradley, Margaret M. Lang, Peter J. Davenport, Paul W. TI Neural processing of respiratory sensations when breathing becomes more difficult and unpleasant SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE brain; breathing difficulty; breathlessness; dyspnea; EEG; neural processing; perception; respiratory-related evoked potential AB The accurate perception of respiratory sensations is important for the successful management and treatment of respiratory diseases. Previous studies demonstrated that external stimuli such as affective pictures and distracting films can impact the perception and neural processing of respiratory sensations. This study examined the neural processing of respiratory sensations when breathing as an internal stimulus is manipulated and becomes more difficult and unpleasant. Sustained breathing through an inspiratory resistive load was used to increase perceived breathing difficulty in 12 female individuals without respiratory disease. Using high-density EEG, respiratory-related evoked potentials (RREP) to short inspiratory occlusions were recorded at early versus late time points of sustained loaded breathing. Ratings of perceived intensity and unpleasantness of breathing difficulty showed an increase from early to late time points of loaded breathing (p < 0.01 and p < 0.05, respectively). This was paralleled by significant increases in the magnitudes of RREP components N1, P2, and P3 (p < 0.01, p < 0.05, and p < 0.05, respectively). The present results demonstrate increases in the neural processing of respiratory sensations when breathing becomes more difficult and unpleasant. This might reflect a protective neural mechanism allowing effective response behavior when air supply is at risk. C1 [von Leupoldt, Andreas; Davenport, Paul W.] Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA. [Bradley, Margaret M.] Univ Hamburg, Dept Psychol, D-20146 Hamburg, Germany. [von Leupoldt, Andreas] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany. [von Leupoldt, Andreas; Bradley, Margaret M.; Lang, Peter J.] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. RP von Leupoldt, A (reprint author), Univ Hamburg, Dept Psychol, Von Melle Pk 5, D-20146 Hamburg, Germany. EM andreas.vonleupoldt@uni-hamburg.de FU German Research Society (Deutsche Forschungsgemeinschaft, DFG) [DFG LE 1843/9-1]; National Institute of Mental Health [P50 MH 72850] FX This study was supported by a stipend (Heisenberg-Stipendium, DFG LE 1843/9-1) from the German Research Society (Deutsche Forschungsgemeinschaft, DFG) to Andreas von Leupoldt and a grant from the National Institute of Mental Health (P50 MH 72850) to Peter J. Lang. The authors wish to thank Andreas Keil for his valuable support of the present study and all our participants. NR 36 TC 7 Z9 7 U1 1 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2010 VL 1 AR 144 DI 10.3389/fphys.2010.00144 PG 5 WC Physiology SC Physiology GA V35UB UT WOS:000209172400040 PM 21423384 ER PT S AU Reilly, MT Lovinger, DM AF Reilly, Matthew T. Lovinger, David M. BE Reilly, MT Lovinger, DM TI Functional Plasticity and Genetic Variation: Insights into the Neurobiology of Alcoholism PREFACE SO FUNCTIONAL PLASTICITY AND GENETIC VARIATION: INSIGHTS INTO THE NEUROBIOLOGY OF ALCOHOLISM SE International Review of Neurobiology LA English DT Editorial Material; Book Chapter C1 [Reilly, Matthew T.] NIAAA, Div Neurosci & Behav, NIH, Bethesda, MD 20892 USA. [Lovinger, David M.] NIAAA, Lab Integrat Neurosci, Div Intramural Clin & Biomed Res, Rockville, MD 20852 USA. RP Reilly, MT (reprint author), NIAAA, Div Neurosci & Behav, NIH, 5635 Fishers Lane,Suite 2065,MSC 9304, Bethesda, MD 20892 USA. NR 2 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 SN 0074-7742 BN 978-0-12-381276-6 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2010 VL 91 BP XI EP XII PG 2 WC Substance Abuse; Genetics & Heredity; Neurosciences SC Substance Abuse; Genetics & Heredity; Neurosciences & Neurology GA BVX26 UT WOS:000293021700001 PM 20813237 ER PT J AU Hill, DA Desai, SA AF Hill, David A. Desai, Sanjay A. TI Malaria parasite mutants with altered erythrocyte permeability: a new drug resistance mechanism and important molecular tool SO FUTURE MICROBIOLOGY LA English DT Review DE host-pathogen interactions; ion channels; malaria; mutant selection; patch clamp; Plasmodium falciparum ID SURFACE ANION CHANNEL; RED-BLOOD-CELLS; FALCIPARUM-INFECTED ERYTHROCYTES; PLASMODIUM-FALCIPARUM; HOST ERYTHROCYTE; BLASTICIDIN-S; PROTEIN-SYNTHESIS; MAMMALIAN-CELLS; OMPF PORIN; IN-VITRO AB Erythrocytes infected with plasmodia, including those that cause human malaria, have increased permeability to a diverse collection of organic and inorganic solutes. While these increases have been known for decades, their mechanistic basis was unclear until electrophysiological studies revealed flux through one or more ion channels on the infected erythrocyte membrane. Current debates have centered on the number of distinct ion channels, which channels mediate the transport of each solute and whether the channels represent parasite-encoded proteins or human channels activated after infection. This article reviews the identification of the plasmodial surface anion channel and other proposed channels with an emphasis on two distinct channel mutants generated through in vitro selection. These mutants implicate parasite genetic elements in the parasite-induced permeability, reveal an important new antimalarial drug resistance mechanism and provide tools for molecular studies. We also critically examine the technical issues relevant to the detection of ion channels by electrophysiological methods; these technical considerations have general applicability for interpreting studies of various ion channels proposed for the infected erythrocyte membrane. C1 [Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Hill, David A.] Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM davhill@mail.med.upenn.edu; sdesai@niaid.nih.gov OI Hill, David/0000-0001-9286-4268 FU NIH; NIAID FX This research was funded by the Intramural Research Program of the NIH, NIAID. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in orfinancial conflict with the suhject matter or materials discussed in the manuscript apartfrom those disclosed. NR 78 TC 8 Z9 8 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD JAN PY 2010 VL 5 IS 1 BP 81 EP 97 DI 10.2217/FMB.09.109 PG 17 WC Microbiology SC Microbiology GA 544ZM UT WOS:000273700500012 PM 20020831 ER PT B AU Alcain, FJ Minor, RK Villalba, JM de Cabo, R AF Alcain, Francisco J. Minor, Robin K. Villalba, Jose M. de Cabo, Rafael BE Fahy, GM West, MD Coles, LS Harris, SB TI Small Molecule Modulators of Sirtuin Activity SO FUTURE OF AGING: PATHWAYS TO HUMAN LIFE EXTENSION LA English DT Article; Book Chapter ID IN-SITU HYBRIDIZATION; HISTONE DEACETYLASE; SIR2 HOMOLOG; LIFE-SPAN; CALORIE RESTRICTION; GENE-EXPRESSION; CHROMOSOMAL ORGANIZATION; ADP-RIBOSYLTRANSFERASE; MITOCHONDRIAL-FUNCTION; BIOLOGICAL EVALUATION C1 [Alcain, Francisco J.; Villalba, Jose M.] Univ Cordoba, Fac Ciencias, Dept Biol Celular Fisiol & Inmunol, Cordoba 14014, Spain. [de Cabo, Rafael] NIA, Expt Lab, NIH, Baltimore, MD 21224 USA. [Minor, Robin K.] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Villalba, JM (reprint author), Univ Cordoba, Fac Ciencias, Dept Biol Celular Fisiol & Inmunol, Campus Univ Rabanales,Edificio Severo Ochoa, Cordoba 14014, Spain. EM bclaltef/@uco.es; minorro@mail.nih.gov; bclvimoj@uco.es; decabora@mail.nih.gov RI de Cabo, Rafael/J-5230-2016 OI de Cabo, Rafael/0000-0002-3354-2442 NR 130 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-90-481-3998-9 PY 2010 BP 331 EP 356 DI 10.1007/978-90-481-3999-6_10 D2 10.1007/978-90-481-3999-6 PG 26 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA BRL24 UT WOS:000283007100010 ER PT S AU Gaynutdinov, TI Neumann, RD Panyutin, IG AF Gaynutdinov, Timur I. Neumann, Ronald D. Panyutin, Igor G. BE Baumann, P TI Assessing DNA Structures with I-125 Radioprobing SO G-QUADRUPLEX DNA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Iodine-125; Radioprobing; DNA structure; Telomere; Quadruplex ID TRIPLEX-FORMING OLIGONUCLEOTIDE; HUMAN TELOMERIC SEQUENCE; SYNTHETIC OLIGODEOXYNUCLEOTIDE; STRAND BREAKS; G-QUADRUPLEX; K+ SOLUTION; DECAY; COMPLEXES AB Iodine-125 radioprobing is based oil incorporation of radioiodine into a defined position in a nucleic acid molecule. Decay of I-125 results ill the emission Of Multiple, low-energy Auger electrons that, along with positively charged residual daughter nuclide, produce DNA strand breaks. The probability Of Such strand breaks at a given nucleotide is in inverse proportion to the distance from the I-125 atom to the sugar of that nucleotide. Therefore, conclusions call be drawn about the conformation or folding of a DNA or RNA molecule based oil the distribution of I-125 decay-induced strand breaks. Here we describe ill detail the application I-125 radioprobing for Studying the conformation of quadruplex structures, and discuss the advantages and limitations of the method. C1 [Gaynutdinov, Timur I.; Neumann, Ronald D.; Panyutin, Igor G.] NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gaynutdinov, TI (reprint author), NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 21 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-950-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 608 BP 137 EP 145 DI 10.1007/978-1-59745-363-9_9 D2 10.1007/978-1-59745-363-9 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNM40 UT WOS:000274950300009 PM 20012420 ER PT B AU Lawrence, JJ AF Lawrence, J. Josh BE Monti, JM PandiPerumal, SR Mohler, H TI Subcortical Neuromodulation of Feedforward and Feedback Inhibitory Microcircuits by the Reticular Activating System SO GABA AND SLEEP: MOLECULAR, FUNCTIONAL AND CLINICAL ASPECTS LA English DT Article; Book Chapter ID HIPPOCAMPAL CA1 INTERNEURONS; STRATUM-ORIENS INTERNEURONS; NICOTINIC ACETYLCHOLINE-RECEPTORS; RAT HIPPOCAMPUS; GABAERGIC INTERNEURONS; PYRAMIDAL CELLS; CHOLINERGIC MODULATION; GABA-RELEASE; IN-VITRO; SYNAPTIC POTENTIALS AB GABAergic inhibition originates from distinct subclasses of interneuron subtypes. These interneuron subtypes are highly specialized, exhibiting distinct pre- and postsynaptic properties. The convergence of these specializations enables each interneuron subtype to make a unique but complementary contribution to the function of cortical microcircuits. The existence of morphologically and physiologically distinct interneuron classes raises the possibility of their being controlled independently of one another. Indeed, based on mounting evidence from Somogyi and colleagues for distinct interneuron classes, Nicoll presented a hypothesis that different neuromodulatory systems might exert precise control over principal cell excitability by engaging different interneuron subtypes. Although our knowledge of the manner in which defined interneuron subtypes undergo neuromodulation remains incomplete, there is accumulating evidence that neuromodulatory receptors are differentially expressed on specific GABAergic interneuron subtypes. Therefore, the efficacy of specific GABAergic feedforward and feedback inhibitory circuits will be dynamically regulated by fluctuations in the concentrations of monoamines occurring across the sleep/wake cycle. During periods of wakefulness, alertness, and attention, I propose that the activation of the reticular activating system will engage specific interneuron subtypes in a cell-type specific manner, collectively optimizing sensory processing and information storage in neural microcircuits. C1 Univ Montana, COBRE Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. RP Lawrence, JJ (reprint author), Univ Montana, COBRE Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, 32 Campus Dr,Skaggs Bldg 385-391, Missoula, MT 59812 USA. EM josh.lawrence@umontana.edu NR 96 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-3-0346-0225-9 PY 2010 BP 147 EP 168 DI 10.1007/978-3-0346-0226-6_6 D2 10.1007/978-3-0346-0226-6 PG 22 WC Physiology SC Physiology GA BRN75 UT WOS:000283201000006 ER PT S AU Crawley, JN AF Crawley, J. N. BE Hokfelt, T TI Galanin Impairs Cognitive Abilities in Rodents: Relevance to Alzheimer's Disease SO GALANIN SE Experientia Supplementum LA English DT Article; Book Chapter DE Alzheimer's; Fear conditioning; Learning and memory; Morris water maze; Receptor knockout mice; Social transmission of food preference; Transgenic mice ID OVEREXPRESSING TRANSGENIC MICE; RAT VENTRAL HIPPOCAMPUS; NONMATCHING-TO-SAMPLE; ELEVATED PLUS-MAZE; SPONTANEOUS-ALTERNATION PERFORMANCE; VITRO AUTORADIOGRAPHIC ANALYSIS; CHOLINERGIC BASAL FOREBRAIN; AMYLOID PRECURSOR PROTEIN; RELEASE IN-VIVO; ACETYLCHOLINE-RELEASE AB The neuropeptide galanin and its receptors are localized in brain pathways that mediate learning and memory. Central microinjection of galanin impairs performance of a variety of cognitive tasks in rats. Transgenic mice overexpressing galanin display deficits in some learning and memory tests. The inhibitory role of galanin in cognitive processes, taken together with the fact that overexpression of galanin occurs in Alzheimer's disease, suggests that galmin antagonists may offer a novel therapeutic approach to treat memory loss in patients suffering from Alzheimer's. C1 NIMH, Lab Behav Neurosci, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Crawley, JN (reprint author), NIMH, Lab Behav Neurosci, Porter Neurosci Res Ctr, Bldg 35,Room IC-903,Mail Code 3730, Bethesda, MD 20892 USA. EM crawleyj@intra.nimh.nih.gov FU Intramural NIH HHS NR 78 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1023-294X BN 978-3-0346-0227-3 J9 EXPERIENTIA SUPPL JI Exp. Suppl. PY 2010 VL 102 BP 133 EP 141 DI 10.1007/978-3-0346-0228-0_10 PG 9 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BQZ17 UT WOS:000282188400010 PM 21299066 ER PT J AU Schoen, RE Pinsky, PF Weissfeld, JL Yokochi, LA Reding, DJ Hayes, RB Church, T Yurgalevich, S Doria-Rose, VP Hickey, T Riley, T Berg, CD AF Schoen, Robert E. Pinsky, Paul F. Weissfeld, Joel L. Yokochi, Lance A. Reding, Douglas J. Hayes, Richard B. Church, Timothy Yurgalevich, Susan Doria-Rose, V. Paul Hickey, Tom Riley, Thomas Berg, Christine D. TI Utilization of Surveillance Colonoscopy in Community Practice SO GASTROENTEROLOGY LA English DT Article ID CANCER SCREENING TRIAL; COLORECTAL-CANCER; NATIONAL-SURVEY; UNITED-STATES; TASK-FORCE; POLYPECTOMY; GUIDELINES; PHYSICIANS; RATIONALE; DEMAND AB BACKGROUND & AIMS: The recommended timing of surveillance colonoscopy For Individuals with adenomatous Polyps is based oil adenoma histology, size, and number. The burden and Cost OF Surveillance colonoscopy are significant. The aim of this Study was to examine the use of surveillance colonoscopy on a, community-wide basis. METHODS: We retrospectively queried participants in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial in 9 US communities about use Of surveillance colonoscopy. Subjects whose initial colonoscopy showed advanced adenoma (AA), nonadvanced adenoma, (NAA), or no adenoma (NA) findings were included. Colonoscopy examinations were confirmed by reviewing colonoscopy reports. RESULTS: Of 3876 subjects selected for Inquiry, 3627 (93.6%) responded. The cumulative probability of a surveillance colonoscopy within 5 years was 58.4% (n = 1342) in the AA group, 57.5% in those with >= 3 NAAs (n = 117), 46.7% in those with 1-2 NAAs (n = 905), and 26.5% (n = 1263) in Subjects with NAs. Within 7 years, 33.2% of subjects with AAs received >= 2 Surveillance examinations versus 26.9% For those with >= 3 NAAs, 18.2% for those With 1 or 2 NAAs, and 10.4% For those with NAs. Incomplete colonoscopy, Family history of colorectal cancer, or interval adenomatous findings could explain only a minority of surveillance colonoscopy in low-risk subjects. CONCLUSIONS: In community practice, there is substantial overuse of surveillance colonoscopy among low-risk subjects and underuse among subjects with AAs. Interventions to better align use of surveillance colonoscopy with risk for advanced lesions are needed. C1 [Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. [Schoen, Robert E.; Weissfeld, Joel L.] Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Pinsky, Paul F.; Doria-Rose, V. Paul; Berg, Christine D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Yokochi, Lance A.] Pacific Hlth Res Inst, Honolulu, HI USA. [Reding, Douglas J.] Marshfield Clin Fdn Med Res & Educ, Dept Hematol & Oncol, Marshfield, WI USA. [Church, Timothy] Univ Minnesota, Dept Hlth Studies Environm Hlth Sci, Minneapolis, MN USA. [Yurgalevich, Susan] Westat Corp, Dept Hlth Studies, Rockville, MD USA. [Hickey, Tom; Riley, Thomas] Informat Management Serv Inc, Rockville, MD USA. RP Schoen, RE (reprint author), Presbyterian Univ Hosp, Div Gastroenterol Hepatol & Nutr, Mezzanine Level,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM rschoen@pitt.edu OI Doria-Rose, Vincent/0000-0002-8802-5143; Church, Timothy R./0000-0003-3292-5035 FU National Cancer Institute [N01-CN2551] FX Supported by a contract from the National Cancer Institute (N01-CN2551). NR 23 TC 98 Z9 99 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2010 VL 138 IS 1 BP 73 EP 81 DI 10.1053/j.gastro.2009.09.062 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 541PA UT WOS:000273427700017 PM 19818779 ER PT J AU Ghany, MG Lok, ASF Everhart, JE Everson, GT Lee, WM Curto, TM Wright, EC Stoddard, AM Sterling, RK Di Bisceglie, AM Bonkovsky, HL Morishima, C Morgan, TR Dienstag, JL AF Ghany, Marc G. Lok, Anna S. F. Everhart, James E. Everson, Gregory T. Lee, William M. Curto, Teresa M. Wright, Elizabeth C. Stoddard, Anne M. Sterling, Richard K. Di Bisceglie, Adrian M. Bonkovsky, Herbert L. Morishima, Chihiro Morgan, Timothy R. Dienstag, Jules L. CA Halt C Trial Grp TI Predicting Clinical and Histologic Outcomes Based on Standard Laboratory Tests in Advanced Chronic Hepatitis C SO GASTROENTEROLOGY LA English DT Article ID VIRUS-RELATED CIRRHOSIS; STAGE LIVER-DISEASE; INSULIN-RESISTANCE; NATURAL-HISTORY; UNITED-STATES; HEPATOCELLULAR-CARCINOMA; FIBROSIS PROGRESSION; COMPENSATED CIRRHOSIS; RISK-FACTORS; STEATOSIS AB BACKGROUND & AIMS: Predictors of clinical outcomes and histologic progression among patients with chronic hepatitis C and advanced fibrosis are poorly defined. We developed statistical models to predict clinical and histologic outcomes in such patients. METHODS: Baseline demographic, clinical, and histologic data from Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial participants were Subjected to multivariate analyses to determine their ability to predict clinical outcomes (ascites, spontaneous bacterial peritonitis, Child-Turcotte-Pugh score >= 7 on 2 consecutive visits, variceal bleeding, hepatic encephalopathy, and liver-related death) and histologic outcome (>= 2-point increase in Ishak fibrosis stage) during the 33 years of the trial. RESULTS: of 1050 randomized patients, 135 had 1 or more clinical Outcomes a median of 23 (range, 1-45) months after randomization. Factors associated with a clinical outcome in multivariate analyses were higher aspartate aminotransferase/alanine aminotransferase ratio, lower albumin, lower platelet Count, higher total bilirubin, and more advanced Ishak fibrosis score (P < .0001). The Cumulative 3.5-year incidence of a clinical outcome was 2% in the lowest and 65% in the highest risk group. OF 547 patients without cirrhosis at baseline and at least 1 follow-up biopsy, 152 had a histologic outcome. Independent variables associated with a histologic Outcome were higher body mass index, lower platelet count, and greater hepatic steatosis (P < .0001). CONCLUSIONS: In patients with chronic hepatitis C and advanced fibrosis, risk of clinical complications and fibrosis progression during 3.5 years can be predicted using baseline laboratory tests and histologic data. Our models may be useful in counseling patients and determining the frequency of monitoring. C1 [Ghany, Marc G.] NIDDK, LDB, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Lok, Anna S. F.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Everson, Gregory T.] Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Curto, Teresa M.; Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA. [Wright, Elizabeth C.] NIDDK, Off Director, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Sterling, Richard K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Ghany, MG (reprint author), NIDDK, LDB, NIH, US Dept HHS, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM marcg@intra.niddk.nih.gov OI Yang, Shuman/0000-0002-9638-0890 FU University of Massachusetts Medical Center, Worcester, Massachusetts [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, Connecticut [M01RR-06192]; St. Louis University School of Medicine, St. Louis, Missouri [N01-DK-9-2324]; Massachusetts General Hospital, Boston, Massachusetts [N01-DK-9-2319, M01RR-01066, UL1 RR025758-01] FX In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct, and/or care of patients enrolled in this study at each of the participating institutions as follows:; University of Massachusetts Medical Center, Worcester, Massachusetts: (contract N01-DK-9-2326) Gyongyl Szabo, MD; Barbara F. Banner, MD; Maureen Cormier, RN; Donna Giansiracusa, RN.; University of Connecticut Health Center, Farmington, Connecticut: (grant M01RR-06192) Gloria Borders, RN; Michelle Kelley, RN, ANP. St. Louis University School of Medicine, St. Louis, Missouri:; St. Louis University School of Medicine, St. Louis, Missouri: (contract N01-DK-9-2324) Bruce Bacon, MD; Brent Neuschwander-Tetri, MD; Debra King, RN.; Massachusetts General Hospital, Boston, Massachusetts: (contract N01-DK-9-2319, grant M01RR-01066; grant I UL1 RR025758-01, Harvard Clinical and Translational Science Center) Raymond T. Chung, MD; Andrea E. Reid, MD; Atul K. Bhan, MD; Wallis A. Molchen, Cara C. Gooch.; University of Colorado School of Medicine, Denver, Colorado: (contract N01-DK-9-2327, grant M01RR-00051, grant 1 UL1 RR 025780-01) S. Russell Nash, MD; Jennifer DeSanto, RN; Carol McKinley, RN. University of California-Irvine, Irvine, California: (contract NO1-DK9-2320, grant M01RR-00827) John C. Hoefs, MD; John R. Craig, MD; M. Mazen Jamal, MD, MPH; Muhammad Sheikh, MD, Choon Park, RN. University of Texas Southwestern Medical Center, Dallas, Texas: (contract N01-DK-9-2321, grant MOIRR-00633, grant I UL1 RR024982-01, North and Central Texas Clinical and Translational Science Initiative) Thomas E. Rogers, MD; Janel Shelton, Nicole Crowder, LVN; Rivka Elbein, RN, BSN; Nancy Liston, MPH. University of Southern California, Los Angeles, California: (contract NOI-DK-9-2325, grant M01RR-00043) Karen L. Lindsay, MD, MMM; Sugantha Govindarajan, MD; Carol B. Jones, RN; Susan L. Milstein, RN. University of Michigan Medical Center, Ann Arbor, Michigan: (contract N01-DK-9-2323, grant MOIRR-00042, grant 1 ULI RR024986, Michigan Center for Clinical and Health Research) Robert J. Fontana, MD; Joel K. Greenson, MD; Pamela A. Richtmyer, LPN, CCRC; R. Tess Bonham, BS. Virginia Commonwealth University Health System, Richmond, Virginia: (contract N01-DK-9-2322, grant M01RR-00065) Mitchell L. Shiffman, MD; Melissa J. Contos, MD; A. Scott Mills, MD; Charlotte Hofmann, RN; Paula Smith, RN. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland: T. Jake Liang, MD; David Weiner, MD, PhD; Yoon Park, RN; Elenita Rivera, RN; Vanessa Haynes-Williams, RN. National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, Maryland: Leonard B. Seeff, MD; Patricia R. Robuck, PhD; Jay H. Hoofnagle, MD. University of Washington, Seattle, Washington: (contract N01-DK9-2318) David R. Gretch, MD, PhD; Minjun Chung Apodaca, BS, ASCP; Rohit Shankar, BC, ASCP; Natalia Antonov, MEd. New England Research Institutes, Watertown, Massachusetts: (contract NOI-DK-9-2328) Kristin K. Snow, MSc, ScD; Linda J. Massey; Deepa Naishadham, MA, MS. Armed Forces Institute of Pathology, Washington, DC: Zachary D. Goodman, MD. Data and Safety Monitoring board members: (chair) Gary L. Davis, MD; Guadalupe Garcia-Tsao, MD; Michael Kutner, PhD; Stanley M. Lemon, MD; Robert P. Perrillo, MD. H.L.B.'s current address is Carolinas Medical Center, Charlotte, North Carolina. This is publication number 40 from the HALT-C Trial Group. The HALT-C Trial was registered with clinicaltrials.gov (No. NCTO0006164). Conflicts of interest The authors disclose the following: financial relationships of the authors with Hoffmann-La Roche, Inc, are as follows: A. S. F. Lok is a consultant; G. T. Everson is a consultant, on the speaker's bureau, and receives research support; W. M. Lee receives research support; R. K. Sterling is consultant, on the speaker's bureau, and receives research support; A.M. Di Bisceglie is a consultant, on the speaker's bureau, and receives research support; H. L. Bonkovsky receives research support; and T. R. Morgan is a consultant, on the speaker's bureau, and receives research support. The remaining authors disclose no conflicts. In addition, many of the HALT-C Trial investigators have other associations with industry relating to the area of hepatitis C, and, to achieve the highest level of disclosure, we list these for you as well. A. S. F.; Lok: Schering-Plough Corporation, consultant and receives research support; Vertex Pharmaceuticals, consultant; denix Pharmaceuticals, receives research support; Eisai Pharmaceuticals, receives research support. G. T. Everson: receives research support from Schering-Plough, Pharmasset, Globelmmune, Source, Novartis/ Human Genome Sciences, and GlaxoSmithKline and is a consultant and receives research support from Vertex Pharmaceuticals. W. M. Lee: receives research support from Aegerion, Globelmmune, Orasure, Schering-Plough, Siemens Diagnostics, and Vertex Pharmaceuticals. A.M. Stoddard: equity interest in Johnson & Johnson, Procter & Gamble, Bristol-Myers Squibb, and Elan. R. K. Sterling: consultant and on the speaker's bureau for Schering-Plough; is on an advisory board for Vertex Pharmaceuticals; and is a consultant and receives research support from Wako Chemicals USA. A. M. Di Bisceglie: consultant, on the speaker's bureau, and receives research support from Idenix Pharmaceuticals; is a consultant for Schering-Plough, Novartis, Bristol-Myers Squibb, and Abbott; is a consultant and receives research support from Vertex Pharmaceuticals, Anadys, Globelmmune, Pharmasset, Scl-Clone, Gilead Sciences, and Novartis. H. L. Bonkovsky: serves on a data monitoring and safety committee for Glaxo Smith Kline; served as a paid consultant for Boehringer-Ingelheim and Infacare Pharmaceuticals receives research support from Merck; consultant and receives research support from Novartis Pharmaceuticals; consultant and on speaker's bureau for Ovation, Inc; receives research support from ScheringPlough Corporation; receives research support from Vertex Pharmaceuticals. T. R. Morgan: is on the speaker's bureau and receives research support from Schering-Plough and is a consultant and receives research support from Vertex Pharmaceuticals. J. L. Dienstag: receives research support from Vertex Pharmaceuticals; serves on a Data Monitoring Committee for Schering-Plough Research Institute and Human Genome Sciences; and is on ad hoc hepatitis advisory board for Boehringer-Ingelheim. Funding Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below) and the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. NR 38 TC 55 Z9 56 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2010 VL 138 IS 1 BP 136 EP 146 DI 10.1053/j.gastro.2009.09.007 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 541PA UT WOS:000273427700024 PM 19766643 ER PT J AU Ahlenstiel, G Titerence, RH Koh, C Edlich, B Feld, JJ Rotman, Y Ghany, MG Hoofnagle, JH Liang, TJ Heller, T Rehermann, B AF Ahlenstiel, Golo Titerence, Rachel H. Koh, Christopher Edlich, Birgit Feld, Jordan J. Rotman, Yaron Ghany, Marc G. Hoofnagle, Jay H. Liang, T. Jake Heller, Theo Rehermann, Barbara TI Natural Killer Cells Are Polarized Toward Cytotoxicity in Chronic Hepatitis C in an Interferon-Alfa-Dependent Manner SO GASTROENTEROLOGY LA English DT Article ID VIRUS ENVELOPE PROTEIN; NK CELLS; ANTIVIRAL DEFENSE; HUMAN HEPATOCYTES; IMMUNE-RESPONSES; GENE-EXPRESSION; T-CELLS; B-VIRUS; INFECTION; LIVER AB BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection display great variability in disease activity and progression. Although virus-specific adaptive immune responses have been characterized extensively and found to be impaired in chronic hepatitis C, the role of innate immune responses in disease activity and progression of chronic hepatitis C is not well understood. METHODS: We studied 42 HCV-infected patients and 12 healthy uninfected controls. RESULTS: We found in increased frequency of natural killer (NK) cells expressing tumor necrosis Factor-related apoptosis-inducing ligand (TRAIL), NKp44, NKG2C,and CD122 in chronic hepatitis C as compared with health), controls (P < .05 For all markers) and stronger activation of NK cells in the liver than in the blood (P < .05). This NK cell phenotype was associated with polarization of NK cell function toward CD107a expression as a marker of degranulation, but with not increased interferon (IFN)-gamma production of CD56(dim) NK cells. The polarized NK cell phenotype correlated with alanine aminotransferase levels (r(2) = 0.312, P = .03). To investigate whether in vivo exposure of NK cells to HCV-induced type I IFN was causing this NK cell phenotype, peripheral blood mononuclear cells from 10 healthy controls and 8 HCV-infected patients Were stimulated in the presence of IFN-alfa, which resulted in increased NK cell expression of TRAIL and CD107a (P < .001), but not IFN-gamma. CONCLUSIONS: Collectively, these results describe a polarized NK cell phenotype induced by chronic exposure to HCV-induced IFN-alfa. This phenotype may contribute to liver injury through TRAIL expression and cytotoxicity, whereas the lacking increase in IFN-gamma production may facilitate the inability to clear HCV. C1 [Rehermann, Barbara] NIDDKD, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDKD, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 9B16C, Bethesda, MD 20892 USA. EM rehermann@nih.gov OI Rotman, Yaron/0000-0002-7549-8216; Ahlenstiel, Golo/0000-0003-0026-1457 FU National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Deutsche Forschungsgemein-Schaft, Bonn, Germany [AH173/1-1] FX This study was supported by the intramural research program of the National Institute for Diabetes and Digestive and Kidney Diseases, National Institutes of Health; and Golo Ahlenstiel is the recipient of grant AH173/1-1 from the Deutsche Forschungsgemein-Schaft, Bonn, Germany. NR 43 TC 107 Z9 116 U1 0 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2010 VL 138 IS 1 BP 325 EP 335 DI 10.1053/j.gastro.2009.08.066 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 541PA UT WOS:000273427700042 PM 19747917 ER PT J AU Yin, S Gao, B AF Yin, Shi Gao, Bin TI Toll-Like Receptor 3 in Liver Diseases SO GASTROENTEROLOGY RESEARCH AND PRACTICE LA English DT Review ID HEPATITIS-C VIRUS; NATURAL-KILLER-CELLS; PRIMARY BILIARY-CIRRHOSIS; CHRONIC ETHANOL-CONSUMPTION; LARGE GRANULAR LYMPHOCYTES; ACTIVATED STELLATE CELLS; INNATE IMMUNITY; CELLS/INTERFERON-GAMMA; RESPONSE MODIFIERS; ADAPTER PROTEIN AB Toll-like receptor 3 (TLR3) is amember of the TLR family that can recognize double-stranded RNA (dsRNA), playing an important role in antiviral immunity. Recent studies have shown that TLR3 is also expressed on parenchymal and nonparenchymal cells in the liver as well as on several types of immune cells. In this review, we summarize the role of TLR3 in liver injury, inflammation, regeneration, and liver fibrosis, and discuss the implication of TLR3 in the pathogenesis of human liver diseases including viral hepatitis and autoimmune liver disease. C1 [Yin, Shi; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Yin, Shi] Anhui Med Univ, Affiliated Prov Hosp, Dept Geriatr, Hefei 230001, Anhui, Peoples R China. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov FU NIAAA, NIH FX This work was supported by the intramural program of NIAAA, NIH. No conflicts of interest exist for all authors. NR 58 TC 6 Z9 6 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 1687-6121 J9 GASTROENT RES PRACT JI Gastroenterol. Res. Pract. PY 2010 AR 750904 DI 10.1155/2010/750904 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 689LT UT WOS:000284929800001 ER PT J AU Leung, K Pinsky, P Laiyemo, AO Lanza, E Schatzkin, A Schoen, RE AF Leung, Keith Pinsky, Paul Laiyemo, Adeyinka O. Lanza, Elaine Schatzkin, Arthur Schoen, Robert E. TI Ongoing colorectal cancer risk despite surveillance colonoscopy: the Polyp Prevention Trial Continued Follow-up Study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID FECAL-OCCULT-BLOOD; HIGH-FIBER; SCREENING COLONOSCOPY; CLINICAL-PRACTICE; LOW-FAT; ADENOMAS; RECURRENCE; POLYPECTOMY; NEOPLASIA; QUALITY AB Background: Despite regular colonoscopy, interval colorectal cancer (CRC) may occur. Long-term studies examining CRC rates in patients with previous colonoscopy are lacking. Objective: examined the rate of interval CRC ill the Polyp Prevention Trial Continued Follow-up Study (PPT-CFS), all observational study of PPT participants that began after the PPT ended. Design: Prospective. Setting: A national U.S. community-based polyp prevention trial. Main Outcome Measurements: Medical records of patients with CRC were Collected, reviewed, and abstracted ill a standardized fashion. Results: Among 2079 PPT participants, 1297 (62.4%) agreed to participate ill the PPT-CFS. They were followed For a median of 6.2 years after 4.3 years of ineclian FOHOW-1-11D in the rri fin PPT. Limitation: A relatively small of interval cancers were cletectecl. Conclusions: Despite frequent colonoscopy during the PPT, in a persistent ongoing risk of cancer. Subjects With a history of advanced adenoma ire at increased(l risk Of subsequent cancer should he followed closely with continued surveillance. (Gastrointest Endose 2010;71:1.11-7.) C1 [Schoen, Robert E.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Dept Med, Pittsburgh, PA 15213 USA. [Schoen, Robert E.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Schoen, Robert E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Pinsky, Paul] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Laiyemo, Adeyinka O.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Lanza, Elaine] NCI, Lab Canc Prevent, Bethesda, MD 20892 USA. [Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Schoen, RE (reprint author), Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Dept Med, Mezzanine Level,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. FU Intramural NIH HHS [Z99 CA999999] NR 30 TC 52 Z9 54 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JAN PY 2010 VL 71 IS 1 BP 111 EP 117 DI 10.1016/j.gie.2009.05.010 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 545YF UT WOS:000273772400017 PM 19647250 ER PT J AU Wang, HB Kondo, A Yoshida, A Yoshizaki, S Abe, S Bao, LL Mizuki, N Ichino, M Klinman, D Okuda, K Shimada, M AF Wang, H-B Kondo, A. Yoshida, A. Yoshizaki, S. Abe, S. Bao, L-L Mizuki, N. Ichino, M. Klinman, D. Okuda, K. Shimada, M. TI Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys SO GENE THERAPY LA English DT Article DE vaccine; virus vector; SIV; monkey model ID SIMIAN IMMUNODEFICIENCY VIRUS; MEMORY T-CELLS; ATTENUATED SIV; IMMUNE-RESPONSES; MUCOSAL CHALLENGE; POXVIRUS VECTORS; ADULT MACAQUES; DNA VACCINES; IN-VITRO; HIV AB This study explores the effect of priming rhesus monkeys with an Ad5/35 vector expressing simian immunodeficiency virus (SIV) gag and gp120, and then boosting the animals with an modified vaccinia virus Ankara (MVA) vector encoding the same antigens after a 2-month interval. The animals were intravenously challenged with 100 TCID50 of highly pathogenic SIVmac239 virus 2 months after the booster vaccination. The priming vaccination induced robust SIV-specific cell-mediated and humoral immune responses, and boosting further enhanced the cellular immunity. Vaccination reduced peak and long-term viral loads by 1-2 logs for a period of >6 months, as reflected by a reduction in both the SIV RNA and DNA levels. Of considerable interest, the immunized monkeys did not suffer from loss of CD4 T cells, particularly central memory CD4 T cells. These results demonstrate that prophylactic vaccination with Ad5/35 followed by MVA reduces viral replication and prevents CD4 T-cell loss, and that these effects may decrease the likelihood of disease progression. Gene Therapy (2010) 17, 4-13; doi: 10.1038/gt.2009.122; published online 17 September 2009 C1 [Bao, L-L] Peking Union Med Coll, Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100021, Peoples R China. [Mizuki, N.] Yokohama City Univ, Grad Sch Med, Dept Ophthalmol, Yokohama, Kanagawa 2360004, Japan. [Ichino, M.] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 2360004, Japan. [Klinman, D.] NCI, NIH, Frederick, MD 21701 USA. RP Shimada, M (reprint author), Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM mshimada@yokohama-cu.ac.jp FU Ministry of Education, Science, Sports and Culture of Japan; Yokohama City University, Japan; Research Foundation for Advanced Medical Research Center; Japanese National Institute of Biomedical Innovation [05-1] FX We thank Dr Chuan Qin, Dr Hong Gao and Dr Li-San Pan (Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences) for animal care and treatment. This work was partially supported by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan; a grant for the Strategic Research Project of Yokohama City University, Japan; a grant from Research Foundation for Advanced Medical Research Center and a grant from the Japanese National Institute of Biomedical Innovation (no. 05-1). NR 55 TC 4 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2010 VL 17 IS 1 BP 4 EP 13 DI 10.1038/gt.2009.122 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 541IJ UT WOS:000273408200002 PM 19759567 ER PT J AU Voutetakis, A Zheng, C Cotrim, AP Mineshiba, F Afione, S Roescher, N Swaim, WD Metzger, M Eckhaus, MA Donahue, RE Dunbar, CE Chiorini, JA Baum, BJ AF Voutetakis, A. Zheng, C. Cotrim, A. P. Mineshiba, F. Afione, S. Roescher, N. Swaim, W. D. Metzger, M. Eckhaus, M. A. Donahue, R. E. Dunbar, C. E. Chiorini, J. A. Baum, B. J. TI AAV5-mediated gene transfer to the parotid glands of non-human primates SO GENE THERAPY LA English DT Article DE AAV; serotype 5; non-human primates; salivary glands; gene therapeutics ID ADENOASSOCIATED VIRUS TYPE-2; SALIVARY-GLANDS; ADENOVIRAL VECTOR; TRANSDUCTION; EXPRESSION; THERAPY; LIVER; DNA; ERYTHROPOIETIN; THERAPEUTICS AB Salivary glands are potentially useful target sites for multiple clinical applications of gene transfer. Previously, we have shown that serotype 2 adeno-associated viral (AAV2) vectors lead to stable gene transfer in the parotid glands of rhesus macaques. As AAV5 vectors result in considerably greater transgene expression in murine salivary glands than do AAV2 vectors, herein we have examined the use of AAV5 vectors in macaques at two different doses (n = 3 per group; 10(10) or 3 x 10(11) particles per gland). AAV5 vector delivery, as with AAV2 vectors, led to no untoward clinical, hematological or serum chemistry responses in macaques. The extent of AAV5-mediated expression of rhesus erythropoietin (RhEpo) was dose-dependent and similar to that seen with an AAV2 vector. However, unlike results with the AAV2 vector, AAV5 vector-mediated RhEpo expression was transient. Maximal expression peaked at day 56, was reduced by similar to 80% on day 84 and thereafter remained near background levels until day 182 (end of experiment). Quantitative PCR studies of high-dose vector biodistribution at this last time point showed much lower AAV5 copy numbers in the targeted parotid gland (similar to 1.7%) than found with the same AAV2 vector dose. Molecular analysis of the conformation of vector DNA indicated a markedly lower level of concatamerization for the AAV5 vector compared with that of a similar AAV2 vector. In addition, cellular immunological studies suggest that host response differences may occur with AAV2 and AAV5 vector delivery at this mucosal site. The aggregate data indicate that results with AAV5 vectors in murine salivary glands apparently do not extend to macaque glands. Gene Therapy (2010) 17, 50-60; doi: 10.1038/gt.2009.123; published online 17 September 2009 C1 [Baum, B. J.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA. [Metzger, M.; Donahue, R. E.; Dunbar, C. E.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Eckhaus, M. A.] NIH, Div Vet Resources, DHHS, 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; National, Heart, Lung, and Blood Institute; National Institutes of Health FX These studies were supported by the Divisions of Intramural Research of the National Institute of Dental and Craniofacial Research and the National, Heart, Lung, and Blood Institute, National Institutes of Health. We thank the animal care staff and technicians for their excellent care and handling of the animals in Building 102 of the NIH Animal Facility in Poolesville, MD, USA. NR 32 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2010 VL 17 IS 1 BP 50 EP 60 DI 10.1038/gt.2009.123 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 541IJ UT WOS:000273408200006 PM 19759566 ER PT B AU Roescher, N Tak, PP Chiorini, JA AF Roescher, Nienke Tak, Paul Peter Chiorini, John A. BE Chernajovsky, Y Robbins, PD TI Gene therapy: Sjogren's syndrome SO GENE THERAPY FOR AUTOIMMUNE AND INFLAMMATORY DISEASES SE Milestones in Drug Therapy LA English DT Article; Book Chapter ID GLAND CELL-LINE; VASOACTIVE-INTESTINAL-PEPTIDE; ANTI-MUSCARINIC ANTIBODIES; NECROSIS-FACTOR-ALPHA; SALIVARY-GLAND; RHEUMATOID-ARTHRITIS; MURINE MODEL; AUTOIMMUNE EXOCRINOPATHY; DOUBLE-BLIND; RECEPTOR AUTOANTIBODIES AB Sjogrens syndrome (SS) is characterized by inflammation and dysfunction of the secretory organs. In the majority of patients the salivary and lachrymal elands are predominantly affected, although systemic symptoms;ire common. The pathogenesis of the disease is not well understood and to date there IS no universally effective therapy available. The development of gene therapy and in particular local gene therapy applied to the salivary glands may be effective in the disease. Animal studies have shown that treatment with immunomodulatory molecules like interleukin 10 or vasoactive intestinal peptide can influence salivary function positively while changing the local inflammatory environment. Future research will have to show whether this approach is feasible in humans. C1 [Roescher, Nienke; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Roescher, Nienke; Tak, Paul Peter] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1100 DD Amsterdam, Netherlands. RP Roescher, N (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. EM roeschern@mail.nih.gov; p.p.tak@amc.uva.nl; jchiorin@mail.nih.gov NR 79 TC 0 Z9 0 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 978-3-0346-0164-1 J9 MILESTONES DRUG THER JI Milest. Drug Ther. PY 2010 BP 113 EP 125 DI 10.1007/978-3-0346-0165-8_8 D2 10.1007/978-3-0346-0165-8 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BPW74 UT WOS:000280183400008 ER PT J AU Anzick, SL Chen, WD Park, Y Meltzer, P Bell, D El-Naggar, AK Kaye, FJ AF Anzick, Sarah L. Chen, Wei-Dong Park, Yoonsoo Meltzer, Paul Bell, Diana El-Naggar, Adel K. Kaye, Frederic J. TI Unfavorable Prognosis of Mucoepidermoid Tumors CRTC1-MAML2 Positive with CDKN2A Deletions SO GENES CHROMOSOMES & CANCER LA English DT Article ID MECT1-MAML2 FUSION ONCOGENE; SALIVARY-GLANDS; LUNG-CANCER; T(11/19) TRANSLOCATION; WARTHINS TUMORS; DNA METHYLATION; GENE MUTATION; P16 GENE; CARCINOMA; EGFR AB The CRTC1-MAML2 fusion oncogene underlies the etiology of mucoepidermoid salivary gland carcinoma (MEC) where it confers a favorable survival outcome as compared with fusion-negative MEC. While these analyses suggested that detection of CRTC1-MAML2 serves as a useful prognostic biomarker we recently identified outlier cases of fusion-positive MEC associated with advanced-staged lethal disease. To identify additional genetic alterations that might cooperate with CRTC1-MAML2 to promote disease progression, we performed a pilot high-resolution oligonucleotide array CGH (aCGH) and PCR-based genotyping study on 23 MEC samples including 14 fusion-positive samples for which we had clinical outcome information. Unbiased aCGH analysis identified inactivating deletions within CDKN2A as a candidate poor prognostic marker which was confirmed by PCR-based analysis (CDKN2A deletions in 5/5 unfavorable fusion-positive cases and 0/9 favorable fusion-positive cases). We did not detect either activating EGFR mutations, nor copy number gains at the EGFR or ERBB2 loci as poor prognostic features for fusion-positive MEC in any of the tumor specimens. Prospective studies with larger case series will be needed to confirm that combined CRTC1-MAML2 and CDKN2A genotyping will optimally stage this disease. (C) 2009 Wiley-Liss, Inc. C1 [Anzick, Sarah L.; Chen, Wei-Dong; Park, Yoonsoo; Meltzer, Paul; Kaye, Frederic J.] NCI, Genet Branch, Canc Res Ctr, Bethesda, MD 20892 USA. [Bell, Diana; El-Naggar, Adel K.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Pathol, Houston, TX 77030 USA. RP Kaye, FJ (reprint author), Room 364,Canc & Genet Res Complex,1376 Mowry Rd, Gainesville, FL 32610 USA. EM fkaye@ufl.edu RI kaye, frederic/E-2437-2011; CHEN, WEI-DONG/F-4521-2014 OI CHEN, WEI-DONG/0000-0003-2264-5515 FU Intramural NIH HHS [Z01 SC007256-19] NR 38 TC 27 Z9 27 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JAN PY 2010 VL 49 IS 1 BP 59 EP 69 DI 10.1002/gcc.20719 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 525KM UT WOS:000272214800007 PM 19827123 ER PT J AU Saini, AK Nanda, JS Lorsch, JR Hinnebusch, AG AF Saini, Adesh K. Nanda, Jagpreet S. Lorsch, Jon R. Hinnebusch, Alan G. TI Regulatory elements in eIF1A control the fidelity of start codon selection by modulating tRNA(i)(Met) binding to the ribosome SO GENES & DEVELOPMENT LA English DT Article DE Translation; initiation; eIF1A; eIF2; initiator; scanning ID EUKARYOTIC TRANSLATION INITIATION; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; IN-VIVO; PREINITIATION COMPLEX; CRYSTAL-STRUCTURE; SITE SELECTION; SUBUNIT; YEAST; RELEASE AB eIF1A is the eukaryotic ortholog of bacterial translation initiation factor IF1, but contains a helical domain and long unstructured N-terminal tail (NTT) and C-terminal tail (CTT) absent in IF1. Here, we identify elements in these accessory regions of eIF1A with dual functions in binding methionyl initiator tRNA (Met-tRNA(i)(Met)) to the ribosome and in selecting AUG codons. A pair of repeats in the eIF1A CTT, dubbed Scanning Enhancer 1 (SE1) and SE2, was found to stimulate recruitment of Met-tRNA(i)(Met) in the ternary complex (TC) with eIF2.GTP and also to block initiation at UUG codons. In contrast, the NTT and segments of the helical domain are required for the elevated UUG initiation occurring in SE mutants, and both regions also impede TC recruitment. Remarkably, mutations in these latter elements, dubbed scanning inhibitors SI1 and SI2, reverse the defects in TC loading and UUG initiation conferred by SE substitutions, showing that the dual functions of SE elements in TC binding and UUG suppression are mechanistically linked. It appears that SE elements enhance TC binding in a conformation conducive to scanning but incompatible with initiation, whereas SI elements destabilize this conformation to enable full accommodation of Met-tRNA(i)(Met) in the P site for AUG selection. C1 [Nanda, Jagpreet S.; Lorsch, Jon R.] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. [Saini, Adesh K.; Hinnebusch, Alan G.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Lorsch, JR (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. EM jlorsch@jhmi.edu; ahinnebusch@nih.gov RI Nanda, Jagpreet/F-9833-2011; OI Lorsch, Jon/0000-0002-4521-4999 FU NIH [GM62128] FX We thank Tom Dever for suggestions and comments on the manuscript. This work was supported in part by the Intramural Research Program of the NIH, and NIH grant GM62128 to J.R.L. NR 38 TC 51 Z9 52 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2010 VL 24 IS 1 BP 97 EP 110 DI 10.1101/gad.1871910 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 539JD UT WOS:000273249300011 PM 20048003 ER PT B AU Stratakis, CA AF Stratakis, Constantine A. BE Weiss, RE Refetoff, S TI Genetic Conditions Associated with Congenital Adrenocortical Insufficiency or Glucocorticoid and/or Mineralocorticoid Resistance SO GENETIC DIAGNOSIS OF ENDOCRINE DISORDERS LA English DT Article; Book Chapter ID TRIPLE-A-SYNDROME; ADRENAL HYPOPLASIA CONGENITA; LEMLI-OPITZ-SYNDROME; INTRAUTERINE GROWTH-RETARDATION; PRIMARY CORTISOL RESISTANCE; COMPLEX PROTEIN ALADIN; WD-REPEAT PROTEIN; RECEPTOR GENE; PSEUDOHYPOALDOSTERONISM TYPE-1; MOLECULAR-MECHANISMS C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD 20892 USA. NR 86 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-092228-7; 978-0-12-374430-2 PY 2010 BP 193 EP 203 DI 10.1016/B978-0-12-374430-2.00018-3 PG 11 WC Endocrinology & Metabolism; Primary Health Care SC Endocrinology & Metabolism; General & Internal Medicine GA BEY98 UT WOS:000318783200019 ER PT J AU Eizirik, E David, VA Buckley-Beason, V Roelke, ME Schaffer, AA Hannah, SS Narfstrom, K O'Brien, SJ Menotti-Raymond, M AF Eizirik, Eduardo David, Victor A. Buckley-Beason, Valerie Roelke, Melody E. Schaeffer, Alejandro A. Hannah, Steven S. Narfstroem, Kristina O'Brien, Stephen J. Menotti-Raymond, Marilyn TI Defining and Mapping Mammalian Coat Pattern Genes: Multiple Genomic Regions Implicated in Domestic Cat Stripes and Spots SO GENETICS LA English DT Article ID FELIS-CATUS; RADIATION HYBRID; LINKAGE MAP; COLOR; MUTATION; DOGS; DROSOPHILA; ZEBRAFISH; PHENOTYPE; EVOLUTION AB Mammalian coat patterns (e. g., spots, stripes) are hypothesized to play important roles in camouflage and other relevant processes, yet the genetic and developmental bases for these phenotypes are completely unknown. The domestic cat, with its diversity of coat patterns, is an excellent model organism to investigate these phenomena. We have established three independent pedigrees to map the four recognized pattern variants classically considered to be specified by a single locus, Tabby; in order of dominance, these are the unpatterned agouti form called "Abyssinian'' or "ticked'' (T(a)), followed by Spotted (T(s)), Mackerel (T(M)), and Blotched (t(b)). We demonstrate that at least three different loci control the coat markings of the domestic cat. One locus, responsible for the Abyssinian form (herein termed the Ticked locus), maps to an similar to 3.8-Mb region on cat chromosome B1. A second locus controls the Tabby alleles T(M) and t(b), and maps to an similar to 5-Mb genomic region on cat chromosome A1. One or more additional loci act as modifiers and create a spotted coat by altering mackerel stripes. On the basis of our results and associated observations, we hypothesize that mammalian patterned coats are formed by two distinct processes: a spatially oriented developmental mechanism that lays down a species-specific pattern of skin cell differentiation and a pigmentation-oriented mechanism that uses information from the preestablished pattern to regulate the synthesis of melanin profiles. C1 [Eizirik, Eduardo] Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, BR-90619900 Porto Alegre, RS, Brazil. [Eizirik, Eduardo] Inst Procarnivoros, BR-12945010 Sao Paulo, Brazil. [Roelke, Melody E.] NCI, SAIC Frederick, Lab Genom Divers, Frederick, MD 21702 USA. [Schaeffer, Alejandro A.] NIH, PetCare Co, Natl Ctr Biotechnol Informat, US Dept HHS, Bethesda, MD 20894 USA. [Hannah, Steven S.] Nestle Purina, St Louis, MO 63164 USA. [Narfstroem, Kristina] Univ Missouri, Dept Ophthalmol, Mason Eye Inst, Columbia, MO 65211 USA. RP Eizirik, E (reprint author), Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, Av Ipiranga 6681,Predio 12, BR-90619900 Porto Alegre, RS, Brazil. EM eduardo.eizirik@pucrs.br RI Schaffer, Alejandro/F-2902-2012; Eizirik, Eduardo/K-8034-2012 OI Eizirik, Eduardo/0000-0002-9658-0999 FU National Institutes of Health (NIH) [N01-CO-12400]; National Cancer Institute (NCI); National Library of Medicine FX We thank Audrey Law for making available the male Egyptian Mau cat used as the founder of pedigree 2, as well as Lyn Colenda and Kevin J. Cogan at the National Institutes of Health Animal Center for their efforts in maintaining and managing pedigrees 2 and 3. We thank the Nestle Purina PetCare Center and personnel for providing us with samples of DNA, as well as assistance in phenotyping the cats from pedigree 1. We thank Marti Welch, Advanced Technology Program, SAIC, Frederick, MD, for assistance in taking photographs. We additionally thank the Frederick County Animal Control Center, Frederick, MD, which allowed us to take photographs of a mackerel cat. David Wells, Ali Wilkerson, Jan Martenson, and William Murphy assisted with various aspects of project design and execution. This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), and National Library of Medicine. This project has been funded in whole or in part with federal funds from the NCI and NIH under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States government. NR 41 TC 20 Z9 21 U1 2 U2 28 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2010 VL 184 IS 1 BP 267 EP U422 DI 10.1534/genetics.109.109629 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 649PH UT WOS:000281784000024 PM 19858284 ER PT J AU Chodroff, RA Goodstadt, L Sirey, TM Oliver, PL Davies, KE Green, ED Molnar, Z Ponting, CP AF Chodroff, Rebecca A. Goodstadt, Leo Sirey, Tamara M. Oliver, Peter L. Davies, Kay E. Green, Eric D. Molnar, Zoltan Ponting, Chris P. TI Long noncoding RNA genes: conservation of sequence and brain expression among diverse amniotes SO GENOME BIOLOGY LA English DT Article ID CEREBRAL-CORTEX; HUMAN GENOME; IN-VIVO; MOUSE; IDENTIFICATION; TRANSCRIPTOME; DIFFERENTIATION; ANNOTATION; NEOCORTEX; EVOLUTION AB Background: Long considered to be the building block of life, it is now apparent that protein is only one of many functional products generated by the eukaryotic genome. Indeed, more of the human genome is transcribed into noncoding sequence than into protein-coding sequence. Nevertheless, whilst we have developed a deep understanding of the relationships between evolutionary constraint and function for protein-coding sequence, little is known about these relationships for non-coding transcribed sequence. This dearth of information is partially attributable to a lack of established non-protein-coding RNA (ncRNA) orthologs among birds and mammals within sequence and expression databases. Results: Here, we performed a multi-disciplinary study of four highly conserved and brain-expressed transcripts selected from a list of mouse long intergenic noncoding RNA (lncRNA) loci that generally show pronounced evolutionary constraint within their putative promoter regions and across exon-intron boundaries. We identify some of the first lncRNA orthologs present in birds (chicken), marsupial (opossum), and eutherian mammals (mouse), and investigate whether they exhibit conservation of brain expression. In contrast to conventional protein-coding genes, the sequences, transcriptional start sites, exon structures, and lengths for these non-coding genes are all highly variable. Conclusions: The biological relevance of lncRNAs would be highly questionable if they were limited to closely related phyla. Instead, their preservation across diverse amniotes, their apparent conservation in exon structure, and similarities in their pattern of brain expression during embryonic and early postnatal stages together indicate that these are functional RNA molecules, of which some have roles in vertebrate brain development. C1 [Chodroff, Rebecca A.; Sirey, Tamara M.; Davies, Kay E.; Molnar, Zoltan; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. [Chodroff, Rebecca A.; Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Goodstadt, Leo; Oliver, Peter L.; Davies, Kay E.; Ponting, Chris P.] Univ Oxford, MRC, Funct Genom Unit, Oxford OX1 3QX, England. RP Molnar, Z (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Le Gros Clark Bldg,S Parks Rd, Oxford OX1 3QX, England. EM zoltan.molnar@dpag.ox.ac.uk; chris.ponting@anat.ox.ac.uk OI Molnar, Zoltan/0000-0002-6852-6004; Ponting, Chris/0000-0003-0202-7816 FU NIH-Oxford; BBSRCBB/F003285/1 [BB/F003285/1, BB/F007590/1]; National Human Genome Research Institute of the National Institutes of Health; UK Medical Research Council; European Research Council (DARCGENs) FX Leah Krubitzer and Sarah Karlen (UC Davies), and Helen Stolp, Carl Joakim Ek and Norman Saunders (University of Melbourne) for M. domestica tissue; Jo Begbie (University of Oxford) for G. gallus tissue; Lisa Bluy (University of Oxford) for histological assistance; Juan Montiel (Pontificia Universidad Catolica de Chile) for comments on G. gallus expression patterns, Darryl Leja and Julia Fekecs (NHGRI) for assistance with figures; Shih-Queen Lee-Lin (NHGRI) for technical assistance; and Shurjo Kumar Sen and Belen Hurle (NHGRI) for critical reading of the manuscript. RAC was supported by an NIH-Oxford Graduate Studentship in the laboratories of EDG and ZM. The project was supported from a BBSRC Project Grant BB/F003285/1 to ZM in collaboration with EDG, KED and CPP, and a BBSRC Research Grant BB/F007590/1 to CPP. This work was also supported in part by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health, the UK Medical Research Council, and the European Research Council (DARCGENs). NR 68 TC 111 Z9 121 U1 3 U2 38 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 7 AR R72 DI 10.1186/gb-2010-11-7-r72 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 674UT UT WOS:000283776300003 PM 20624288 ER PT J AU Cirulli, ET Singh, A Shianna, KV Ge, DL Smith, JP Maia, JM Heinzen, EL Goedert, JJ Goldstein, DB AF Cirulli, Elizabeth T. Singh, Abanish Shianna, Kevin V. Ge, Dongliang Smith, Jason P. Maia, Jessica M. Heinzen, Erin L. Goedert, James J. Goldstein, David B. CA Ctr HIV AIDS Vaccine Immunology TI Screening the human exome: a comparison of whole genome and whole transcriptome sequencing SO GENOME BIOLOGY LA English DT Article AB Background: There is considerable interest in the development of methods to efficiently identify all coding variants present in large sample sets of humans. There are three approaches possible: whole-genome sequencing, whole-exome sequencing using exon capture methods, and RNA-Seq. While whole-genome sequencing is the most complete, it remains sufficiently expensive that cost effective alternatives are important. Results: Here we provide a systematic exploration of how well RNA-Seq can identify human coding variants by comparing variants identified through high coverage whole-genome sequencing to those identified by high coverage RNA-Seq in the same individual. This comparison allowed us to directly evaluate the sensitivity and specificity of RNA-Seq in identifying coding variants, and to evaluate how key parameters such as the degree of coverage and the expression levels of genes interact to influence performance. We find that although only 40% of exonic variants identified by whole genome sequencing were captured using RNA-Seq; this number rose to 81% when concentrating on genes known to be well-expressed in the source tissue. We also find that a high false positive rate can be problematic when working with RNA-Seq data, especially at higher levels of coverage. Conclusions: We conclude that as long as a tissue relevant to the trait under study is available and suitable quality control screens are implemented, RNA-Seq is a fast and inexpensive alternative approach for finding coding variants in genes with sufficiently high expression levels. C1 [Cirulli, Elizabeth T.; Singh, Abanish; Shianna, Kevin V.; Ge, Dongliang; Smith, Jason P.; Maia, Jessica M.; Heinzen, Erin L.; Goldstein, David B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA. [Goedert, James J.] US Natl Canc Inst Hlth, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Goldstein, DB (reprint author), Duke Univ, Sch Med, Ctr Human Genome Variat, Box 91009, Durham, NC 27708 USA. EM d.goldstein@duke.edu RI Sincan, Murat /A-3794-2010; OI Cirulli Rogers, Liz/0000-0001-7808-2809 FU NIAID Center for HIV/AIDS Vaccine Immunology [AI067854]; Bill and Melinda Gates Foundation [157412] FX Funding was provided by the NIAID Center for HIV/AIDS Vaccine Immunology grant AI067854 and the Bill and Melinda Gates Foundation grant 157412. We also acknowledge C Gumbs, K Cronin and L Little for DNA and RNA extraction. NR 10 TC 58 Z9 60 U1 3 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 5 AR R57 DI 10.1186/gb-2010-11-5-r57 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 622AS UT WOS:000279631000022 PM 20598109 ER PT J AU Faghihi, MA Zhang, M Huang, J Modarresi, F Van der Brug, MP Nalls, MA Cookson, MR St-Laurent, G Wahlestedt, C AF Faghihi, Mohammad Ali Zhang, Ming Huang, Jia Modarresi, Farzaneh Van der Brug, Marcel P. Nalls, Michael A. Cookson, Mark R. St-Laurent, Georges, III Wahlestedt, Claes TI Evidence for natural antisense transcript-mediated inhibition of microRNA function SO GENOME BIOLOGY LA English DT Editorial Material ID BETA-SECRETASE ACTIVITY; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; GENE-EXPRESSION; NONCODING RNA; MAMMALIAN TRANSCRIPTOME; NERVOUS-SYSTEM; DRUG TARGET; BACE1; HIF-1-ALPHA AB Background: MicroRNAs (miRNAs) have the potential to regulate diverse sets of mRNA targets. In addition, mammalian genomes contain numerous natural antisense transcripts, most of which appear to be non-protein-coding RNAs (ncRNAs). We have recently identified and characterized a highly conserved non-coding antisense transcript for beta-secretase-1 (BACE1), a critical enzyme in Alzheimer's disease pathophysiology. The BACE1-antisense transcript is markedly up-regulated in brain samples from Alzheimer's disease patients and promotes the stability of the (sense) BACE1 transcript. Results: We report here that BACE1-antisense prevents miRNA-induced repression of BACE1 mRNA by masking the binding site for miR-485-5p. Indeed, miR-485-5p and BACE1-antisense compete for binding within the same region in the open reading frame of the BACE1 mRNA. We observed opposing effects of BACE1-antisense and miR-485-5p on BACE1 protein in vitro and showed that Locked Nucleic Acid-antimiR mediated knockdown of miR-485-5p as well as BACE1-antisense over-expression can prevent the miRNA-induced BACE1 suppression. We found that the expression of BACE1-antisense as well as miR-485-5p are dysregulated in RNA samples from Alzheimer's disease subjects compared to control individuals. Conclusions: Our data demonstrate an interface between two distinct groups of regulatory RNAs in the computation of BACE1 gene expression. Moreover, bioinformatics analyses revealed a theoretical basis for many other potential interactions between natural antisense transcripts and miRNAs at the binding sites of the latter. C1 [Faghihi, Mohammad Ali; Modarresi, Farzaneh; Van der Brug, Marcel P.; Wahlestedt, Claes] Scripps Florida, Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA. [Wahlestedt, Claes] Scripps Florida, Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA. [Zhang, Ming] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA. [Huang, Jia] Miller Sch Med, Miami Inst Human Gen, Miami, FL 33101 USA. [Nalls, Michael A.; Cookson, Mark R.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [St-Laurent, Georges, III] Brown Univ, Dept Biol, Providence, RI 02912 USA. RP Wahlestedt, C (reprint author), Scripps Florida, Scripps Res Inst, Dept Neurosci, 130 Scripps Way, Jupiter, FL 33458 USA. EM clawah@scripps.edu FU National Institute of Neurological Disorders and Stroke (NINDS) [RO1 NS063974]; National Institute of Aging (NIA) [1RC2 AG036596] FX We are grateful to Drs Barbara G Sahagan, Douglas E Wood, Todd E Morgan and Caleb E Finch for providing human brain samples and to Dr Corinne Lasmezas for providing miRNA over-expression vectors. We are also grateful to Dr Jannet Kocerha for technical help and discussion. This research was supported in part by grants from the National Institute of Neurological Disorders and Stroke (NINDS), RO1 NS063974, and from the National Institute of Aging (NIA), 1RC2 AG036596. This research was also supported in part by the Intramural Research Program of the NIA. All authors affirm that there is no conflict of interest that would prejudice the impartiality of this original work. NR 55 TC 143 Z9 158 U1 1 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 5 AR R56 DI 10.1186/gb-2010-11-5-r56 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 622AS UT WOS:000279631000021 PM 20507594 ER PT J AU Florea, L Souvorov, A Salzberg, SL AF Florea, Liliana Souvorov, Alexander Salzberg, Steven L. TI Genes and genomes, an imperfect world: comparison of gene annotations of two Bos taurus draft assemblies SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Florea, Liliana; Salzberg, Steven L.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Souvorov, Alexander] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RI Salzberg, Steven/F-6162-2011 OI Salzberg, Steven/0000-0002-8859-7432 NR 2 TC 1 Z9 1 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 SU 1 AR P13 DI 10.1186/gb-2010-11-S1-P13 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 674VT UT WOS:000283779100037 ER PT J AU Gan, QA Schones, DE Eun, SH Wei, G Cui, KR Zhao, KJ Chen, X AF Gan, Qiang Schones, Dustin E. Eun, Suk Ho Wei, Gang Cui, Kairong Zhao, Keji Chen, Xin TI Monovalent and unpoised status of most genes in undifferentiated cell-enriched Drosophila testis SO GENOME BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; RNA-POLYMERASE-II; BAG-OF-MARBLES; DNA METHYLATION; DEVELOPMENTAL REGULATORS; LYSINE-27 METHYLATION; PAUSED CONFORMATION; BIVALENT GENES; GROUP PROTEINS; HUMAN GENOME AB Background: Increasing evidence demonstrates that stem cells maintain their identities by a unique transcription network and chromatin structure. Opposing epigenetic modifications H3K27me3 and H3K4me3 have been proposed to label differentiation-associated genes in stem cells, progenitor and precursor cells. In addition, many differentiation-associated genes are maintained at a poised status by recruitment of the initiative RNA Polymerase II (Pol II) at their promoter regions, in preparation for lineage-specific expression upon differentiation. Previous studies have been performed using cultured mammalian embryonic stem cells. To a lesser extent, chromatin structure has been delineated in other model organisms, such as Drosophila, to open new avenues for genetic analyses. Results: Here we use testes isolated from a Drosophila bag of marbles mutant strain, from which germ cells are in their undifferentiated status. We use these testes to study the endogenous chromatin structure of undifferentiated cells using ChIP-seq. We integrate the ChIP-seq with RNA-seq data, which measures the digital transcriptome. Our genome-wide analyses indicate that most differentiation-associated genes in undifferentiated cells lack an active chromatin mark and initiative Pol II; instead, they are associated with either the repressive H3K27me3 mark or no detectable mark. Conclusions: Our results reveal that most of the differentiation-associated genes in undifferentiated-cell-enriched Drosophila testes are associated with monovalent but not bivalent modifications, a chromatin signature that is distinct from the data reported in mammalian stem or precursor cells, which may reflect cell type specificity, species specificity, or both. C1 [Gan, Qiang; Eun, Suk Ho; Chen, Xin] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Schones, Dustin E.; Wei, Gang; Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Chen, X (reprint author), Johns Hopkins Univ, Dept Biol, 3400 N Charles St, Baltimore, MD 21218 USA. EM xchen32@jhu.edu RI Wei, Gang/A-3291-2011; Gan, Qiang/K-9605-2013 FU March of Dimes Foundation [05-FY09-88]; NICHD [R00HD055052]; Edward Mallinckrodt; Jr Foundation; Johns Hopkins University; Division of Intramural Research; National Heart, Lung and Blood Institute, NIH FX We thank Caitlin Choi and Ankit Vartak for technical assistance with testis dissection. We also thank Chen lab members for their critical reading and insightful suggestions. The gene expression profiling using microarrays was performed by the Genomics Core Facility of the National Heart, Lung and Blood Institute. This work is supported in part by research grant no. 05-FY09-88 from the March of Dimes Foundation, the R00HD055052 NIH Pathway to Independence Award from NICHD, the 49th Mallinckrodt Scholar Award from the Edward Mallinckrodt, Jr Foundation and the Johns Hopkins University start-up funding (XC), and support of Division of Intramural Research, the National Heart, Lung and Blood Institute, NIH (KZ). NR 67 TC 38 Z9 38 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 4 AR R42 DI 10.1186/gb-2010-11-4-r42 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 621ZG UT WOS:000279625000013 PM 20398323 ER PT J AU Heimeier, RA Das, B Buchholz, DR Fiorentino, M Shi, YB AF Heimeier, Rachel A. Das, Biswajit Buchholz, Daniel R. Fiorentino, Maria Shi, Yun-Bo TI Studies on Xenopus laevis intestine reveal biological pathways underlying vertebrate gut adaptation from embryo to adult SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION; THYROID-HORMONE; MICROARRAY DATA; EPITHELIAL-CELLS; AMPHIBIAN METAMORPHOSIS; STEM-CELLS; CANCER; DIFFERENTIATION; RENEWAL; PROTEIN AB Background: To adapt to its changing dietary environment, the digestive tract is extensively remodeled from the embryo to the adult during vertebrate development. Xenopus laevis metamorphosis is an excellent model system for studying mammalian gastrointestinal development and is used to determine the genes and signaling programs essential for intestinal development and maturation. Results: The metamorphosing intestine can be divided into four distinct developmental time points and these were analyzed with X. laevis microarrays. Due to the high level of conservation in developmental signaling programs and homology to mammalian genes, annotations and bioinformatics analysis were based on human orthologs. Clustering of the expression patterns revealed co-expressed genes involved in essential cell processes such as apoptosis and proliferation. The two largest clusters of genes have expression peaks and troughs at the climax of metamorphosis, respectively. Novel conserved gene ontology categories regulated during this period include transcriptional activity, signal transduction, and metabolic processes. Additionally, we identified larval/embryo-and adult-specific genes. Detailed analysis revealed 17 larval specific genes that may represent molecular markers for human colonic cancers, while many adult specific genes are associated with dietary enzymes. Conclusions: This global developmental expression study provides the first detailed molecular description of intestinal remodeling and maturation during postembryonic development, which should help improve our understanding of intestinal organogenesis and human diseases. This study significantly contributes towards our understanding of the dynamics of molecular regulation during development and tissue renewal, which is important for future basic and clinical research and for medicinal applications. C1 [Heimeier, Rachel A.; Das, Biswajit; Fiorentino, Maria; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, PCRM,NIH, Bethesda, MD 20892 USA. [Heimeier, Rachel A.] Karolinska Inst, Inst Environm Med IMM, S-17177 Stockholm, Sweden. [Buchholz, Daniel R.] Univ Cincinnati, Dept Biol Sci, Cincinnati, OH 45221 USA. RP Heimeier, RA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, PCRM,NIH, 18 Lib Dr, Bethesda, MD 20892 USA. EM heimeier78@gmail.com; shi@helix.nih.gov OI Fiorentino, Maria R/0000-0001-5318-7313 FU NICHD, NIH FX This research was supported in part by the Intramural Research Program of NICHD, NIH. NR 42 TC 36 Z9 38 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 5 AR R55 DI 10.1186/gb-2010-11-5-r55 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 622AS UT WOS:000279631000020 PM 20482879 ER PT J AU Kandasamy, K Mohan, SS Raju, R Keerthikumar, S Kumar, GSS Venugopal, AK Telikicherla, D Navarro, JD Mathivanan, S Pecquet, C Gollapudi, SK Tattikota, SG Mohan, S Padhukasahasram, H Subbannayya, Y Goel, R Jacob, HKC Zhong, J Sekhar, R Nanjappa, V Balakrishnan, L Subbaiah, R Ramachandra, YL Rahiman, BA Prasad, TSK Lin, JX Houtman, JCD Desiderio, S Renauld, JC Constantinescu, SN Ohara, O Hirano, T Kubo, M Singh, S Khatri, P Draghici, S Bader, GD Sander, C Leonard, WJ Pandey, A AF Kandasamy, Kumaran Mohan, S. Sujatha Raju, Rajesh Keerthikumar, Shivakumar Kumar, Ghantasala S. Sameer Venugopal, Abhilash K. Telikicherla, Deepthi Navarro, J. Daniel Mathivanan, Suresh Pecquet, Christian Gollapudi, Sashi Kanth Tattikota, Sudhir Gopal Mohan, Shyam Padhukasahasram, Hariprasad Subbannayya, Yashwanth Goel, Renu Jacob, Harrys K. C. Zhong, Jun Sekhar, Raja Nanjappa, Vishalakshi Balakrishnan, Lavanya Subbaiah, Roopashree Ramachandra, Y. L. Rahiman, B. Abdul Prasad, T. S. Keshava Lin, Jian-Xin Houtman, Jon C. D. Desiderio, Stephen Renauld, Jean-Christophe Constantinescu, Stefan N. Ohara, Osamu Hirano, Toshio Kubo, Masato Singh, Sujay Khatri, Purvesh Draghici, Sorin Bader, Gary D. Sander, Chris Leonard, Warren J. Pandey, Akhilesh TI NetPath: a public resource of curated signal transduction pathways SO GENOME BIOLOGY LA English DT Article ID SYSTEMS BIOLOGY; T-CELLS; INTERACTION NETWORKS; REPRESENTATION; INTERLEUKIN-2-RECEPTOR; PROLIFERATION; LYMPHOCYTES; ENVIRONMENT; ACTIVATION; SOFTWARE AB We have developed NetPath as a resource of curated human signaling pathways. As an initial step, NetPath provides detailed maps of a number of immune signaling pathways, which include approximately 1,600 reactions annotated from the literature and more than 2,800 instances of transcriptionally regulated genes - all linked to over 5,500 published articles. We anticipate NetPath to become a consolidated resource for human signaling pathways that should enable systems biology approaches. C1 [Kandasamy, Kumaran; Jacob, Harrys K. C.; Zhong, Jun; Pandey, Akhilesh] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Kandasamy, Kumaran; Jacob, Harrys K. C.; Zhong, Jun; Pandey, Akhilesh] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD 21205 USA. [Kandasamy, Kumaran; Mohan, S. Sujatha; Raju, Rajesh; Keerthikumar, Shivakumar; Kumar, Ghantasala S. Sameer; Venugopal, Abhilash K.; Telikicherla, Deepthi; Navarro, J. Daniel; Mathivanan, Suresh; Gollapudi, Sashi Kanth; Tattikota, Sudhir Gopal; Mohan, Shyam; Padhukasahasram, Hariprasad; Subbannayya, Yashwanth; Goel, Renu; Jacob, Harrys K. C.; Sekhar, Raja; Nanjappa, Vishalakshi; Balakrishnan, Lavanya; Subbaiah, Roopashree; Prasad, T. S. Keshava] Inst Bioinformat, Bangalore 560066, Karnataka, India. [Raju, Rajesh; Ramachandra, Y. L.; Rahiman, B. Abdul] Kuvempu Univ, Dept Biotechnol & Bioinformat, Jnanasahyadri 577451, Shimoga, India. [Lin, Jian-Xin; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Houtman, Jon C. D.] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA. [Desiderio, Stephen] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Inst Cell Engn, Baltimore, MD 21205 USA. [Renauld, Jean-Christophe; Constantinescu, Stefan N.] Catholic Univ Louvain, Ludwig Inst Canc Res, Brussels Branch, B-1200 Brussels, Belgium. [Renauld, Jean-Christophe; Constantinescu, Stefan N.] Catholic Univ Louvain, Expt Med Unit, Christian de Duve Inst Cellular Pathol, B-1200 Brussels, Belgium. [Ohara, Osamu] RIKEN Yokohama Inst, Lab Immunogenom, RIKEN Res Ctr Allergy & Immunol, RIKEN Yokohama Inst, Kanagawa 2300045, Japan. [Ohara, Osamu] Kazusa DNA Res Inst, Dept Human Genome Technol, Chiba 2920818, Japan. [Hirano, Toshio] RIKEN Res Ctr Allergy & Immunol, Lab Cytokine Signaling, Kanagawa 2300045, Japan. [Hirano, Toshio] Osaka Univ, Grad Sch Frontier Biosci, Labs Dev Immunol, Osaka 5650871, Japan. [Hirano, Toshio] Osaka Univ, Grad Sch Med, Osaka 5650871, Japan. [Kubo, Masato] Tokyo Univ Sci, Res Inst Biol Sci, Noda, Chiba 2780022, Japan. [Kubo, Masato] RIKEN Yokohama Inst, Signal Network Team, RIKEN Res Ctr Allergy & Immunol, Kanagawa 2300045, Japan. [Singh, Sujay] IMGENEX India Pvt Ltd, Bhubaneswar 92121, Orissa, India. [Khatri, Purvesh; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Draghici, Sorin] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. [Bader, Gary D.] Univ Toronto, Banting & Best Dept Med Res, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada. [Bader, Gary D.; Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10021 USA. [Pandey, Akhilesh] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA. RP Pandey, A (reprint author), Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. EM pandey@jhmi.edu RI Bader, Gary/C-1176-2009; Kandasamy, Kumaran/C-8981-2009; KEERTHIKUMAR, SHIVAKUMAR/B-4673-2011; sander, chris/H-1452-2011; Ohara, Osamu/A-9119-2012; Prasad, T. S. Keshava/F-7631-2010; Ohara, Osamu/G-5448-2015; Subbannayya, Yashwanth/A-7796-2012; Zhong, Jun/D-1662-2010; Pandey, Akhilesh/B-4127-2009; Constantinescu, Stefan /E-5277-2012; Draghici, Sorin/B-3074-2013; Mathivanan, Suresh/D-2045-2009; Charles Jacob, Harrys Kishore/D-5386-2009; OI Bader, Gary/0000-0003-0185-8861; KEERTHIKUMAR, SHIVAKUMAR/0000-0001-9865-9767; Prasad, T. S. Keshava/0000-0002-6206-2384; Ohara, Osamu/0000-0002-3328-9571; Subbannayya, Yashwanth/0000-0002-3885-3514; Zhong, Jun/0000-0003-3148-4143; Pandey, Akhilesh/0000-0001-9943-6127; Draghici, Sorin/0000-0002-0786-8377; Mathivanan, Suresh/0000-0002-7290-5795; Charles Jacob, Harrys Kishore/0000-0003-3030-2539; Palapetta, Shyam Mohan/0000-0002-7674-1310 FU Johns Hopkins Breast Cancer SPORE [CA 88843]; Department of Defense [W81XWH-06-1-0428]; National Institutes of Health [U54 RR020839] FX Akhilesh Pandey is supported by grants from Johns Hopkins Breast Cancer SPORE (CA 88843) Career Development Award, Department of Defense Era of Hope Scholar (W81XWH-06-1-0428) and partly by National Institutes of Health grant U54 RR020839 (Roadmap Initiative for Technology Centers for Networks and Pathways). NR 48 TC 140 Z9 140 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 1 AR R3 DI 10.1186/gb-2010-11-1-r3 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 580FS UT WOS:000276433600011 PM 20067622 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI The origin and early evolution of eukaryotes in the light of phylogenomics SO GENOME BIOLOGY LA English DT Review ID NUCLEAR-PORE-COMPLEX; COMPARATIVE GENOMICS; RNA-POLYMERASES; GENE-TRANSFER; ENDOMEMBRANE SYSTEM; ARCHAEAL EXOSOME; DNA-POLYMERASES; PROTEINS; TRANSCRIPTION; TREE AB Phylogenomics of eukaryote supergroups suggest a highly complex last common ancestor of eukaryotes and a key role of mitochondrial endosymbiosis in the origin of eukaryotes. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU DHHS (National Library of Medicine) FX I thank Yuri Wolf for providing the data used in Figure 2, Bill Martin for helpful discussions and Tania Senkevich for critical reading of the manuscript. The author's research is supported by the DHHS (National Library of Medicine) intramural funds. NR 135 TC 136 Z9 137 U1 19 U2 63 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 5 AR 209 DI 10.1186/gb-2010-11-5-209 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 622AS UT WOS:000279631000008 PM 20441612 ER PT J AU Ostrander, EA Boyko, A Quignon, P Li, L Schoenebeck, JJ Degenhardt, JD Lohmueller, KE Zhao, KY Brisbin, A Parker, HG Von Holdt, BM Cargill, M Auton, A Reynolds, A Elkahloun, AG Mosher, DS Sutter, NB Novembre, J Hubisz, MJ Siepel, A Wayne, RK Bustamante, CD AF Ostrander, Elaine A. Boyko, Adam Quignon, Pascale Li, Lin Schoenebeck, Jeffrey J. Degenhardt, Jeremiah D. Lohmueller, Kurt E. Zhao, Keyan Brisbin, Abra Parker, Heidi G. Von Holdt, Bridgett M. Cargill, Michelle Auton, Adam Reynolds, Andy Elkahloun, Abdel G. Mosher, Dana S. Sutter, Nathan B. Novembre, John Hubisz, Melissa J. Siepel, Adam Wayne, Robert K. Bustamante, Carlos D. TI Tracking genes and finding mutations: finding genes for complex traits in the domestic dog (Canis familiaris) SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Ostrander, Elaine A.; Quignon, Pascale; Schoenebeck, Jeffrey J.; Parker, Heidi G.; Elkahloun, Abdel G.; Mosher, Dana S.] NHGRI, NIH, Bethesda, MD 20892 USA. [Boyko, Adam; Zhao, Keyan; Auton, Adam; Reynolds, Andy; Bustamante, Carlos D.] Stanford Sch Med, Dept Genet, Stanford, CA USA. [Li, Lin; Degenhardt, Jeremiah D.; Lohmueller, Kurt E.; Zhao, Keyan; Brisbin, Abra; Hubisz, Melissa J.; Siepel, Adam; Wayne, Robert K.; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA. [Von Holdt, Bridgett M.; Novembre, John] Univ Calif Los Angeles, Dept Ecol & Environm Biol, Los Angeles, CA USA. [Cargill, Michelle] Affymetrix Corp, Santa Clara, CA USA. [Sutter, Nathan B.] Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA. RI Novembre, John/G-1339-2011 NR 0 TC 0 Z9 0 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 SU 1 AR I23 DI 10.1186/gb-2010-11-S1-I23 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 674VT UT WOS:000283779100014 ER PT J AU Segre, JA Grice, EA Kong, HH Conlan, S Snitkin, E Mijares, L Murray, P Green, ED Turner, ML AF Segre, Julie A. Grice, Elizabeth A. Kong, Heidi H. Conlan, Sean Snitkin, Evan Mijares, Lilia Murray, Patrick Green, Eric D. Turner, Maria L. TI Skin microbiome in health and disease SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Segre, Julie A.; Grice, Elizabeth A.; Conlan, Sean; Snitkin, Evan; Green, Eric D.] NHGRI, NISC Comparat Sequencing Program, NIH, Bethesda, MD 20892 USA. [Kong, Heidi H.; Turner, Maria L.] NCI, Dept Dermatol, CCR, NIH, Bethesda, MD 20892 USA. [Mijares, Lilia; Murray, Patrick] NIH, Dept Lab Microbiol, NIH Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 SU 1 AR I18 DI 10.1186/gb-2010-11-S1-I18 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 674VT UT WOS:000283779100008 ER PT J AU Woolfe, A Mullikin, JC Elnitski, L AF Woolfe, Adam Mullikin, James C. Elnitski, Laura TI Genomic features defining exonic variants that modulate splicing SO GENOME BIOLOGY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; SILENT NUCLEOTIDE SUBSTITUTION; PYRUVATE-DEHYDROGENASE COMPLEX; LINKED MENTAL-RETARDATION; GILFORD PROGERIA SYNDROME; HUMAN-DISEASE GENES; MESSENGER-RNA; REGULATORY ELEMENTS; MISSENSE MUTATIONS; POINT MUTATION AB Background: Single point mutations at both synonymous and non-synonymous positions within exons can have severe effects on gene function through disruption of splicing. Predicting these mutations in silico purely from the genomic sequence is difficult due to an incomplete understanding of the multiple factors that may be responsible. In addition, little is known about which computational prediction approaches, such as those involving exonic splicing enhancers and exonic splicing silencers, are most informative. Results: We assessed the features of single-nucleotide genomic variants verified to cause exon skipping and compared them to a large set of coding SNPs common in the human population, which are likely to have no effect on splicing. Our findings implicate a number of features important for their ability to discriminate splice-affecting variants, including the naturally occurring density of exonic splicing enhancers and exonic splicing silencers of the exon and intronic environment, extensive changes in the number of predicted exonic splicing enhancers and exonic splicing silencers, proximity to the splice junctions and evolutionary constraint of the region surrounding the variant. By extending this approach to additional datasets, we also identified relevant features of variants that cause increased exon inclusion and ectopic splice site activation. Conclusions: We identified a number of features that have statistically significant representation among exonic variants that modulate splicing. These analyses highlight putative mechanisms responsible for splicing outcome and emphasize the role of features important for exon definition. We developed a web-tool, Skippy, to score coding variants for these relevant splice-modulating features. C1 [Woolfe, Adam; Elnitski, Laura] NHGRI, Genom Funct Anal Sect, NIH, Rockville, MD 20892 USA. [Mullikin, James C.] NHGRI, Comparat Genom Unit, NIH, Rockville, MD 20892 USA. RP Woolfe, A (reprint author), NHGRI, Genom Funct Anal Sect, NIH, Rockville, MD 20892 USA. EM woolfea@mail.nih.gov FU National Human Genome Research Institute FX We thank Giovanni Parmigiani for statistical advice, Michael Hiller for help on calculating RNA structure probability of unpaired values and Dirk Holste for help on extracting data from the Hollywood database. Thanks must also go to Tyra Wolfsberg, Chris Pan, Mark Fredriksen and Gongwei Jiang for help setting up the Skippy database. We would also like to thank Lawrence Brody and the NIH Fellows Editorial Board for advice and critical reading of the manuscript. This work was supported by the Intramural Program of the National Human Genome Research Institute. NR 153 TC 48 Z9 51 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 2 AR R20 DI 10.1186/gb-2010-11-2-r20 PG 23 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 580FX UT WOS:000276434300010 PM 20158892 ER PT J AU Zheng, J Khil, PP Camerini-Otero, RD Przytycka, TM AF Zheng, Jie Khil, Pavel P. Camerini-Otero, R. Daniel Przytycka, Teresa M. TI Detecting sequence polymorphisms associated with meiotic recombination hotspots in the human genome SO GENOME BIOLOGY LA English DT Article ID LINKAGE DISEQUILIBRIUM; HOT-SPOTS; CONVERSION PARADOX; PRDM9; RATES; PATTERNS; MAP; INSTABILITY; CHIMPANZEES; CROSSOVERS AB Background: Meiotic recombination events tend to cluster into narrow spans of a few kilobases long, called recombination hotspots. Such hotspots are not conserved between human and chimpanzee and vary between different human ethnic groups. At the same time, recombination hotspots are heritable. Previous studies showed instances where differences in recombination rate could be associated with sequence polymorphisms. Results: In this work we developed a novel computational approach, LDsplit, to perform a large-scale association study of recombination hotspots with genetic polymorphisms. LDsplit was able to correctly predict the association between the FG11 SNP and the DNA2 hotspot observed by sperm typing. Extensive simulation demonstrated the accuracy of LDsplit under various conditions. Applying LDsplit to human chromosome 6, we found that for a significant fraction of hotspots, there is an association between variations in intensity of historical recombination and sequence polymorphisms. From flanking regions of the SNPs output by LDsplit we identified a conserved 11-mer motif GGNGGNAGGGG, whose complement partially matches 13-mer CCNCCNTNNCCNC, a critical motif for the regulation of recombination hotspots. Conclusions: Our result suggests that computational approaches based on historical recombination events are likely to be more powerful than previously anticipated. The putative associations we identified may be a promising step toward uncovering the mechanisms of recombination hotspots. C1 [Khil, Pavel P.; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. [Zheng, Jie; Przytycka, Teresa M.] Natl Lib Med, NCBI, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, 5 Mem Dr, Bethesda, MD 20892 USA. EM camerini@ncifcrf.gov; przytyck@ncbi.nlm.nih.gov RI Zheng, Jie/C-1356-2011; OI Zheng, Jie/0000-0001-6774-9786; Khil, Pavel/0000-0002-4903-8777 FU National Institutes of Health; National Library of Medicine; National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine and the National Institute of Diabetes and Digestive and Kidney Diseases. This study utilized the high-performance computational capabilities of the Biowulf PC/Linux cluster [55] at the National Institutes of Health. NR 55 TC 13 Z9 13 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2010 VL 11 IS 10 AR R103 DI 10.1186/gb-2010-11-10-r103 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 721TS UT WOS:000287378900005 PM 20961408 ER PT J AU Losada, L Ronning, CM DeShazer, D Woods, D Fedorova, N Kim, HS Shabalina, SA Pearson, TR Brinkac, L Tan, P Nandi, T Crabtree, J Badger, J Beckstrom-Sternberg, S Saqib, M Schutzer, SE Keim, P Nierman, WC AF Losada, Liliana Ronning, Catherine M. DeShazer, David Woods, Donald Fedorova, Natalie Kim, H. Stanley Shabalina, Svetlana A. Pearson, Talima R. Brinkac, Lauren Tan, Patrick Nandi, Tannistha Crabtree, Jonathan Badger, Jonathan Beckstrom-Sternberg, Steve Saqib, Muhammad Schutzer, Steven E. Keim, Paul Nierman, William C. TI Continuing Evolution of Burkholderia mallei Through Genome Reduction and Large-Scale Rearrangements SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE bacterial evolution; comparative genomics; genome erosion; bacterial virulence ID MICROBIAL GENE IDENTIFICATION; BACTERIAL GENOMES; PSEUDOMALLEI; MELIOIDOSIS; AGENT; SALMONELLA; CHROMOSOME; AMINOGLYCOSIDE; SUSCEPTIBILITY; POPULATIONS AB Burkholderia mallei (Bm), the causative agent of the predominately equine disease glanders, is a genetically uniform species that is very closely related to the much more diverse species Burkholderia pseudomallei (Bp), an opportunistic human pathogen and the primary cause of melioidosis. To gain insight into the relative lack of genetic diversity within Bm, we performed whole-genome comparative analysis of seven Bm strains and contrasted these with eight Bp strains. The Bm core genome (shared by all seven strains) is smaller in size than that of Bp, but the inverse is true for the variable gene sets that are distributed across strains. Interestingly, the biological roles of the Bm variable gene sets are much more homogeneous than those of Bp. The Bm variable genes are found mostly in contiguous regions flanked by insertion sequence (IS) elements, which appear to mediate excision and subsequent elimination of groups of genes that are under reduced selection in the mammalian host. The analysis suggests that the Bm genome continues to evolve through random IS-mediated recombination events, and differences in gene content may contribute to differences in virulence observed among Bm strains. The results are consistent with the view that Bm recently evolved from a single strain of Bp upon introduction into an animal host followed by expansion of IS elements, prophage elimination, and genome rearrangements and reduction mediated by homologous recombination across IS elements. C1 [Losada, Liliana; Ronning, Catherine M.; Fedorova, Natalie; Brinkac, Lauren; Nierman, William C.] J Craig Venter Inst, Rockville, MD USA. [Losada, Liliana] Trinity Univ, Washington, DC USA. [DeShazer, David] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Woods, Donald] Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB, Canada. [Kim, H. Stanley] Korea Univ, Coll Med, Bioinformat & Funct Genom Lab, Seoul 136705, South Korea. [Shabalina, Svetlana A.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Pearson, Talima R.; Beckstrom-Sternberg, Steve; Keim, Paul] No Arizona Univ, Ctr Microbial Genet & Genom, Flagstaff, AZ 86011 USA. [Tan, Patrick; Nandi, Tannistha] Genome Inst Singapore, Singapore, Singapore. [Tan, Patrick] Duke Natl Univ Singapore, Grad Sch Med, Durham, NC USA. [Crabtree, Jonathan] Univ Maryland Baltimore Cty, Bioinformat Resource Ctr, Baltimore, MD 21228 USA. [Crabtree, Jonathan] J Craig Venter Inst, San Diego, CA USA. [Saqib, Muhammad] Vet Res Ctr, Barka, Oman. [Saqib, Muhammad] Univ Agr Faisalabad, Faisalabad, Pakistan. [Schutzer, Steven E.] Univ Med & Dent New Jersey, Dept Med, Sch Med, Newark, NJ 07103 USA. [Nierman, William C.] George Washington Univ, Dept Biochem & Mol Biol, Sch Med, Washington, DC 20052 USA. RP Losada, L (reprint author), J Craig Venter Inst, Rockville, MD USA. EM llosada@jcvi.org RI Keim, Paul/A-2269-2010; Shabalina, Svetlana/N-8939-2013; Abrams, Natalie/F-4845-2011 OI Shabalina, Svetlana/0000-0003-2272-7473; Abrams, Natalie/0000-0001-9698-2819 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [N01-AI-30071] FX This project has been funded with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract number N01-AI-30071. NR 53 TC 30 Z9 31 U1 6 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2010 VL 2 BP 102 EP 116 DI 10.1093/gbe/evq003 PG 15 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 633DP UT WOS:000280480000010 PM 20333227 ER PT J AU Wolf, YI Gopich, IV Lipman, DJ Koonin, EV AF Wolf, Yuri I. Gopich, Irina V. Lipman, David J. Koonin, Eugene V. TI Relative Contributions of Intrinsic Structural-Functional Constraints and Translation Rate to the Evolution of Protein-Coding Genes SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE protein evolution; structural-functional constraints; misfolding; protein abundance ID SEQUENCE EVOLUTION; EXPRESSION LEVEL; DISPENSABILITY; DATABASE; DIVERGENCE; GENERATION; DROSOPHILA; BACTERIA AB A long-standing assumption in evolutionary biology is that the evolution rate of protein-coding genes depends, largely, on specific constraints that affect the function of the given protein. However, recent research in evolutionary systems biology revealed unexpected, significant correlations between evolution rate and characteristics of genes or proteins that are not directly related to specific protein functions, such as expression level and protein-protein interactions. The strongest connections were consistently detected between protein sequence evolution rate and the expression level of the respective gene. A recent genome-wide proteomic study revealed an extremely strong correlation between the abundances of orthologous proteins in distantly related animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. We used the extensive protein abundance data from this study along with short-term evolutionary rates (ERs) of orthologous genes in nematodes and flies to estimate the relative contributions of structural-functional constraints and the translation rate to the evolution rate of protein-coding genes. Together the intrinsic constraints and translation rate account for approximately 50% of the variance of the ERs. The contribution of constraints is estimated to be 3-to 5-fold greater than the contribution of translation rate. C1 [Wolf, Yuri I.; Lipman, David J.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Gopich, Irina V.] NIDDK, NIH, Bethesda, MD USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Department of Health and Human Services (National Library of Medicine and National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health) FX We thank Sabine Schrimpf, Christian Von Mering, and Manuel Weiss (University of Zurich, Zurich, Switzerland) for providing the protein abundance data including an unpublished subset, and Josh Cherry, Alexander Lobkovsky, Scott Roy (National Center for Biotechnology Information), and Claus Wilke (University of Texas-Austin) for useful discussions. The authors' research is supported by the Department of Health and Human Services intramural funds (National Library of Medicine and National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health). NR 37 TC 20 Z9 21 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2010 VL 2 BP 190 EP 199 DI 10.1093/gbe/evq010 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 633DP UT WOS:000280480000017 PM 20624725 ER PT J AU Davis, JK Lowman, JJ Thomas, PJ ten Hallers, BFH Koriabine, M Huynh, LY Maney, DL de Jong, PJ Martin, CL Thomas, JW AF Davis, Jamie K. Lowman, Josh J. Thomas, Pamela J. ten Hallers, Boudewijn F. H. Koriabine, Maxim Huynh, Lynn Y. Maney, Donna L. de Jong, Pieter J. Martin, Christa L. Thomas, James W. CA NISC Comparative Sequencing TI Evolution of a Bitter Taste Receptor Gene Cluster in a New World Sparrow SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE bitter taste receptors; molecular evolution; inversion; duplication ID WHITE-THROATED SPARROW; ZONOTRICHIA-ALBICOLLIS GMELIN; AMINO-ACID SITES; PHYLOGENETIC ANALYSIS; POSITIVE SELECTION; CHROMOSOMAL-POLYMORPHISM; MAXIMUM-LIKELIHOOD; SEQUENCE; HUMANS; SENSITIVITY AB Bitter taste perception likely evolved as a protective mechanism against the ingestion of harmful compounds in food. The evolution of the taste receptor type 2 (TAS2R) gene family, which encodes the chemoreceptors that are directly responsible for the detection of bitter compounds, has therefore been of considerable interest. Though TAS2R repertoires have been characterized for a number of species, to date the complement of TAS2Rs from just one bird, the chicken, which had a notably small number of TAS2Rs, has been established. Here, we used targeted mapping and genomic sequencing in the white-throated sparrow (Zonotrichia albicollis) and sample sequencing in other closely related birds to reconstruct the history of a TAS2R gene cluster physically linked to the break points of an evolutionary chromosomal rearrangement. In the white-throated sparrow, this TAS2R cluster encodes up to 18 functional bitter taste receptors and likely underwent a large expansion that predates and/or coincides with the radiation of the Emberizinae subfamily into the New World. In addition to signatures of gene birth-and-death evolution within this cluster, estimates of Ka/Ks for the songbird TAS2Rs were similar to those previously observed in mammals, including humans. Finally, comparison of the complete genomic sequence of the cluster from two common haplotypes in the white-throated sparrow revealed a number of nonsynonymous variants and differences in functional gene content within this species. These results suggest that interspecies and intraspecies genetic variability does exist in avian TAS2Rs and that these differences could contribute to variation in bitter taste perception in birds. C1 [Davis, Jamie K.; Lowman, Josh J.; Huynh, Lynn Y.; Martin, Christa L.; Thomas, James W.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. [Thomas, Pamela J.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Thomas, Pamela J.; NISC Comparative Sequencing] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [ten Hallers, Boudewijn F. H.; Koriabine, Maxim; de Jong, Pieter J.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. [Huynh, Lynn Y.] Emory Univ, Grad Program Populat Biol Ecol & Evolut, Atlanta, GA 30322 USA. [Maney, Donna L.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. RP Thomas, JW (reprint author), Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. EM jthomas@genetics.emory.edu RI Maney, Donna/G-3706-2011 FU National Institutes of Health (NIH) [1R21MH082046]; National Human Genome Research Institute of the NIH FX The authors thank Cheryl Strauss for technical writing comments on the manuscript, the anonymous reviewers for their comments, Greg K. Tharp for computer support, the BC Cancer Agency Genome Sciences Centre, Vancouver, Canada for generation of the BESs, and members of the NIH Sequencing Center including E. D. Green, R. Blakesley, G. Bouffard, and J. McDowell. DNA samples were provided by The Burke Museum of Natural History and Culture. This work was supported by the National Institutes of Health (NIH) (1R21MH082046 to J.K.D., J.J.L., D.L.M., C.L.M, and J.W.T.) and the NIH Intramural Sequencing Center was supported in part by the Intramural Research Program of the National Human Genome Research Institute of the NIH. NR 67 TC 13 Z9 13 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2010 VL 2 BP 358 EP 370 DI 10.1093/gbe/evq027 PG 13 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 633DP UT WOS:000280480000032 PM 20624740 ER PT J AU Warnecke, T Huang, Y Przytycka, TM Hurst, LD AF Warnecke, Tobias Huang, Yang Przytycka, Teresa M. Hurst, Laurence D. TI Unique Cost Dynamics Elucidate the Role of Frameshifting Errors in Promoting Translational Robustness SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE translational error; GC content; translational accuracy; codon usage bias; tRNA repertoire ID CODON USAGE BIAS; TRANSFER-RNA DISCRIMINATION; ESCHERICHIA-COLI; GENE-EXPRESSION; HUNGRY CODON; RIBOSOME; ANTICODON; EVOLUTION; SELECTION; ACCURACY AB There is now considerable evidence supporting the view that codon usage is frequently under selection for translational accuracy. There are, however, multiple forms of inaccuracy (missense, premature termination, and frameshifting errors) and pinpointing a particular error process behind apparently adaptive mRNA anatomy is rarely straightforward. Understanding differences in the fitness costs associated with different types of translational error can help us devise critical tests that can implicate one error process to the exclusion of others. To this end, we present a model that captures distinct features of frameshifting cost and apply this to 641 prokaryotic genomes. We demonstrate that, although it is commonly assumed that the ribosome encounters an off-frame stop codon soon after the frameshift and costs of mis-elongation are therefore limited, genomes with high GC content typically incur much larger per-error costs. We go on to derive the prediction, unique to frameshifting errors, that differences in translational robustness between the 5' and 3' ends of genes should be less pronounced in genomes with higher GC content. This prediction we show to be correct. Surprisingly, this does not mean that GC-rich organisms necessarily carry a greater fitness burden as a consequence of accidental frameshifting. Indeed, increased per-error costs are often more than counterbalanced by lower predicted error rates owing to more diverse anticodon repertoires in GC-rich genomes. We therefore propose that selection on tRNA repertoires may operate to reduce frameshifting errors. C1 [Warnecke, Tobias; Hurst, Laurence D.] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. [Huang, Yang; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Warnecke, T (reprint author), Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. EM T.Warnecke@bath.ac.uk FU Medical Research Council; National Library of Medicine/National Institutes of Health FX The authors would like to thank Ed Feil and Eduardo Rocha for useful discussions and two anonymous reviewers for their constructive comments on the manuscript. This work was supported by a Medical Research Council Capacity Building Studentship to T. W. and National Library of Medicine/National Institutes of Health intramural research program to Y.H. and T. M. P. NR 41 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2010 VL 2 BP 636 EP 645 DI 10.1093/gbe/evq049 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 775NT UT WOS:000291467300007 PM 20688751 ER PT J AU Puigbo, P Wolf, YI Koonin, EV AF Puigbo, Pere Wolf, Yuri I. Koonin, Eugene V. TI The Tree and Net Components of Prokaryote Evolution SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE phylogenetic tree; horizontal gene transfer; species quartets; computer simulation ID HORIZONTAL GENE-TRANSFER; MULTIPLE SEQUENCE ALIGNMENT; DEINOCOCCUS-THERMUS PHYLUM; COMPARATIVE GENOMICS; PHYLOGENETIC TREES; LIFE HYPOTHESIS; HIGH-THROUGHPUT; CLASSIFICATION; ADAPTATION; VIEW AB Phylogenetic trees of individual genes of prokaryotes (archaea and bacteria) generally have different topologies, largely owing to extensive horizontal gene transfer (HGT), suggesting that the Tree of Life (TOL) should be replaced by a "net of life'' as the paradigm of prokaryote evolution. However, trees remain the natural representation of the histories of individual genes given the fundamentally bifurcating process of gene replication. Therefore, although no single tree can fully represent the evolution of prokaryote genomes, the complete picture of evolution will necessarily combine trees and nets. A quantitative measure of the signals of tree and net evolution is derived from an analysis of all quartets of species in all trees of the "Forest of Life'' (FOL), which consists of approximately 7,000 phylogenetic trees for prokaryote genes including approximately 100 nearly universal trees (NUTs). Although diverse routes of net-like evolution collectively dominate the FOL, the pattern of tree-like evolution that reflects the consistent topologies of the NUTs is the most prominent coherent trend. We show that the contributions of tree-like and net-like evolutionary processes substantially differ across bacterial and archaeal lineages and between functional classes of genes. Evolutionary simulations indicate that the central tree-like signal cannot be realistically explained by a self-reinforcing pattern of biased HGT. C1 [Puigbo, Pere; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov RI Puigbo, Pere/A-2214-2008 FU US Department of Health and Human Services (National Library of Medicine, National Institutes of Health) FX The authors' research is supported by intramural funds of the US Department of Health and Human Services (National Library of Medicine, National Institutes of Health). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author contributions: P. P., Y.I.W., and E. V. K. designed the study; P. P. performed research; P. P., Y.I.W., and E. V. K. analyzed the data; P. P. and E. V. K. wrote the manuscript. NR 55 TC 68 Z9 69 U1 2 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2010 VL 2 BP 745 EP 756 DI 10.1093/gbe/evq062 PG 12 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 775NT UT WOS:000291467300017 PM 20889655 ER PT J AU Cherry, JL AF Cherry, Joshua L. TI Expression Level, Evolutionary Rate, and the Cost of Expression SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE expression level; protein evolution; population genetics; molecular evolution ID SYNONYMOUS CODON USAGE; GENE DISPENSABILITY; PROTEIN; GENOME AB There is great variation in the rates of sequence evolution among proteins encoded by the same genome. The strongest correlate of evolutionary rate is expression level: highly expressed proteins tend to evolve slowly. This observation has led to the proposal that a major determinant of protein evolutionary rate involves the toxic effects of protein that misfolds due to transcriptional and translational errors (the mistranslation-induced misfolding [MIM] hypothesis). Here, I present a model that explains the correlation of evolutionary rate and expression level by selection for function. The basis of this model is that selection keeps expression levels near optima that reflect a trade-off between beneficial effects of the protein's function and some nonspecific cost of expression (e. g., the biochemical cost of synthesizing protein). Simulations confirm the predictions of the model. Like the MIM hypothesis, this model predicts several other relationships that are observed empirically. Although the model is based on selection for protein function, it is consistent with findings that a protein's rate of evolution is at most weakly correlated with its importance for fitness as measured by gene knockout experiments. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Cherry, JL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM jcherry@ncbi.nlm.nih.gov FU National Institute of Health, National Library of Medicine FX I thank David Lipman, Scott Roy, and Yuri Wolf for comments on the manuscript. This research was supported by the Intramural Research Program of the National Institute of Health, National Library of Medicine. NR 27 TC 17 Z9 18 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2010 VL 2 BP 757 EP 769 DI 10.1093/gbe/evq059 PG 13 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 775NT UT WOS:000291467300018 PM 20884723 ER PT J AU Shabalina, SA Spiridonov, AN Spiridonov, NA Koonin, EV AF Shabalina, Svetlana A. Spiridonov, Alexey N. Spiridonov, Nikolay A. Koonin, Eugene V. TI Connections between Alternative Transcription and Alternative Splicing in Mammals SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE alternative splicing; alternative transcription initiation; alternative transcription termination; gene expression factories ID RNA-POLYMERASE-II; C-TERMINAL DOMAIN; MESSENGER-RNA; UNTRANSLATED REGIONS; INITIATION SITES; START SITES; PROMOTERS; EXPRESSION; EVOLUTION; SEQUENCES AB The majority of mammalian genes produce multiple transcripts resulting from alternative splicing (AS) and/or alternative transcription initiation (ATI) and alternative transcription termination (ATT). Comparative analysis of the number of alternative nucleotides, isoforms, and introns per locus in genes with different types of alternative events suggests that ATI and ATT contribute to the diversity of human and mouse transcriptome even more than AS. There is a strong negative correlation between AS and ATI in 5' untranslated regions (UTRs) and AS in coding sequences (CDSs) but an even stronger positive correlation between AS in CDSs and ATT in 3' UTRs. These observations could reflect preferential regulation of distinct, large groups of genes by different mechanisms: 1) regulation at the level of transcription initiation and initiation of translation resulting from ATI and AS in 5' UTRs and 2) posttranslational regulation by different protein isoforms. The tight linkage between AS in CDSs and ATT in 3' UTRs suggests that variability of 3' UTRs mediates differential translational regulation of alternative protein forms. Together, the results imply coordinate evolution of AS and alternative transcription, processes that occur concomitantly within gene expression factories. C1 [Shabalina, Svetlana A.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Spiridonov, Alexey N.] MIT, Dept Math, Cambridge, MA 02139 USA. [Spiridonov, Nikolay A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM shabalin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; FU US Department of Health and Human Services (National Library of Medicine) FX The research of S.A.S. and E.V.K. is supported by the intramural funds of the US Department of Health and Human Services (National Library of Medicine). NR 44 TC 18 Z9 20 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2010 VL 2 BP 791 EP 799 DI 10.1093/gbe/evq058 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 775NT UT WOS:000291467300021 PM 20889654 ER PT J AU Dalgleish, R Flicek, P Cunningham, F Astashyn, A Tully, RE Proctor, G Chen, Y McLaren, WM Larsson, P Vaughan, BW Beroud, C Dobson, G Lehvaslaiho, H Taschner, PEM den Dunnen, JT Devereau, A Birney, E Brookes, AJ Maglott, DR AF Dalgleish, Raymond Flicek, Paul Cunningham, Fiona Astashyn, Alex Tully, Raymond E. Proctor, Glenn Chen, Yuan McLaren, William M. Larsson, Pontus Vaughan, Brendan W. Beroud, Christophe Dobson, Glen Lehvaeslaiho, Heikki Taschner, Peter E. M. den Dunnen, Johan T. Devereau, Andrew Birney, Ewan Brookes, Anthony J. Maglott, Donna R. TI Locus Reference Genomic sequences: an improved basis for describing human DNA variants SO GENOME MEDICINE LA English DT Article AB As our knowledge of the complexity of gene architecture grows, and we increase our understanding of the subtleties of gene expression, the process of accurately describing disease-causing gene variants has become increasingly problematic. In part, this is due to current reference DNA sequence formats that do not fully meet present needs. Here we present the Locus Reference Genomic (LRG) sequence format, which has been designed for the specific purpose of gene variant reporting. The format builds on the successful National Center for Biotechnology Information (NCBI) RefSeqGene project and provides a single-file record containing a uniquely stable reference DNA sequence along with all relevant transcript and protein sequences essential to the description of gene variants. In principle, LRGs can be created for any organism, not just human. In addition, we recognize the need to respect legacy numbering systems for exons and amino acids and the LRG format takes account of these. We hope that widespread adoption of LRGs - which will be created and maintained by the NCBI and the European Bioinformatics Institute (EBI) - along with consistent use of the Human Genome Variation Society (HGVS)-approved variant nomenclature will reduce errors in the reporting of variants in the literature and improve communication about variants affecting human health. Further information can be found on the LRG web site (http://www.lrg-sequence.org). C1 [Dalgleish, Raymond; Brookes, Anthony J.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [Flicek, Paul; Cunningham, Fiona; Proctor, Glenn; Chen, Yuan; McLaren, William M.; Larsson, Pontus; Vaughan, Brendan W.; Birney, Ewan] European Bioinformat Inst, Cambridge CB10 1SD, England. [Astashyn, Alex; Tully, Raymond E.; Maglott, Donna R.] NIH, Natl Biotechnol Ctr, Natl Lib Med, Bethesda, MD 20894 USA. [Beroud, Christophe] INSERM, U827, F-34000 Montpellier, France. [Dobson, Glen; Devereau, Andrew] St Marys Hosp, NGRL Manchester, Manchester M13 9WL, Lancs, England. [Lehvaeslaiho, Heikki] King Abdullah Univ Sci & Technol, Computat Biosci Res Ctr, Jeddah 21534, Saudi Arabia. [Taschner, Peter E. M.; den Dunnen, Johan T.] Leiden Univ, Dept Human Genet, Med Ctr, Ctr Human & Clin Genet, NL-2300 RA Leiden, Netherlands. RP Dalgleish, R (reprint author), Univ Leicester, Dept Genet, Univ Rd, Leicester LE1 7RH, Leics, England. EM raymond.dalgleish@le.ac.uk RI LABO, U827/A-8632-2008; Taschner, Peter/J-8853-2014; BEROUD, Christophe/A-8381-2008; OI Taschner, Peter/0000-0001-9621-465X; BEROUD, Christophe/0000-0003-2986-8738; Lehvaslaiho, Heikki/0000-0002-6263-1356; Vaughan, Brendan/0000-0002-2199-1267; Cunningham, Fiona/0000-0002-7445-2419; Flicek, Paul/0000-0002-3897-7955; McLaren, William/0000-0001-6218-1116; Birney, Ewan/0000-0001-8314-8497 FU European Community's Seventh Framework Programme [200754] FX We are grateful for the help of the Human Genome Variation Society in distributing the survey that was used in the initial development of the LRG specification. We are also grateful to those who responded to the survey and those who provided feedback on drafts of the specification. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement number 200754 - the GEN2PHEN project. NR 27 TC 59 Z9 60 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2010 VL 2 AR 24 DI 10.1186/gm145 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA V27QG UT WOS:000208627100024 PM 20398331 ER PT J AU Prentice, RL Paczesny, SJ Aragaki, A Amon, LM Chen, L Pitteri, SJ McIntosh, M Wang, P Busald, TB Hsia, J Jackson, RD Rossouw, JE Manson, JE Johnson, K Eaton, C Hanash, SM AF Prentice, Ross L. Paczesny, Sophie J. Aragaki, Aaron Amon, Lynn M. Chen, Lin Pitteri, Sharon J. McIntosh, Martin Wang, Pei Busald, Tina Buson Hsia, Judith Jackson, Rebecca D. Rossouw, Jacques E. Manson, JoAnn E. Johnson, Karen Eaton, Charles Hanash, Samir M. TI Novel proteins associated with risk for coronary heart disease or stroke among postmenopausal women identified by in-depth plasma proteome profiling SO GENOME MEDICINE LA English DT Article AB Background: Coronary heart disease (CHD) and stroke were key outcomes in the Women's Health Initiative (WHI) randomized trials of postmenopausal estrogen and estrogen plus progestin therapy. We recently reported a large number of changes in blood protein concentrations in the first year following randomization in these trials using an in-depth quantitative proteomics approach. However, even though many affected proteins are in pathways relevant to the observed clinical effects, the relationships of these proteins to CHD and stroke risk among postmenopausal women remains substantially unknown. Methods: The same in-depth proteomics platform was applied to plasma samples, obtained at enrollment in the WHI Observational Study, from 800 women who developed CHD and 800 women who developed stroke during cohort follow-up, and from 1-1 matched controls. A plasma pooling strategy, followed by extensive fractionation prior to mass spectrometry, was used to identify proteins related to disease incidence, and the overlap of these proteins with those affected by hormone therapy was examined. Replication studies, using enzyme-linked-immunosorbent assay (ELISA), were carried out in the WHI hormone therapy trial cohorts. Results: Case versus control concentration differences were suggested for 37 proteins (nominal P < 0.05) for CHD, with three proteins, beta-2 microglobulin (B2M), alpha-1-acid glycoprotein 1 (ORM1), and insulin-like growth factor binding protein acid labile subunit (IGFALS) having a false discovery rate < 0.05. Corresponding numbers for stroke were 47 proteins with nominal P < 0.05, three of which, apolipoprotein A-II precursor (APOA2), peptidyl-prolyl isomerase A (PPIA), and insulin-like growth factor binding protein 4 (IGFBP4), have a false discovery rate < 0.05. Other proteins involved in insulin-like growth factor signaling were also highly ranked. The associations of B2M with CHD (P < 0.001) and IGFBP4 with stroke (P = 0.005) were confirmed using ELISA in replication studies, and changes in these proteins following the initiation of hormone therapy use were shown to have potential to help explain hormone therapy effects on those diseases. Conclusions: In-depth proteomic discovery analysis of prediagnostic plasma samples identified B2M and IGFBP4 as risk markers for CHD and stroke respectively, and provided a number of candidate markers of disease risk and candidate mediators of hormone therapy effects on CHD and stroke. C1 [Prentice, Ross L.; Aragaki, Aaron; Amon, Lynn M.; Chen, Lin; Pitteri, Sharon J.; McIntosh, Martin; Wang, Pei; Busald, Tina Buson; Hanash, Samir M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98102 USA. [Paczesny, Sophie J.] Univ Michigan, Dept Pediat, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hsia, Judith] AstraZeneca LP, Res & Dev, Wilmington, DE 19803 USA. [Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol, Columbus, OH 43210 USA. [Rossouw, Jacques E.] NHLBI, WHI Project Off, NIH, Bethesda, MD 20892 USA. [Manson, JoAnn E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Johnson, Karen] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Eaton, Charles] Brown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N, Seattle, WA 98102 USA. EM rprentic@fhcrc.org OI Pitteri, Sharon/0000-0002-3119-873X FU National Heart, Lung, and Blood Institute, National Institutes of Health; US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-, 19, 32122, 42107-26, 42129-32, 44221]; BAA [HHSN268200764315C]; National Cancer Institute [P01 CA53996] FX The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-, 19, 32122, 42107-26, 42129-32, and 44221), and particularly by BAA contract #HHSN268200764315C. Dr Prentice's work was partially supported by grant P01 CA53996 from the National Cancer Institute. Decisions concerning study design, data collection and analysis, interpretation of the results, the preparation of the manuscript, or the decision to submit the manuscript for publication resided with committees composed of WHI investigators that included NHLBI representatives. The authors thank the WHI investigators and staff for their outstanding dedication and commitment. A list of key investigators involved in this research follows. A full listing of WHI investigators can be found at [49]. Program Office: (National Heart, Lung, and Blood Institute, Bethesda, MD) Elizabeth Nabel, Jacques Rossouw, Shari Ludlam, Linda Pottern, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA) Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L Kooperberg, Ruth E Patterson, Anne McTiernan; (Wake Forest University School of Medicine, Winston-Salem, NC) Sally Shumaker; (Medical Research Labs, Highland Heights, KY) Evan Stein; (University of California at San Francisco, San Francisco, CA) Steven Cummings.; Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX) Aleksandar Rajkovic; (Brigham and Women's Hospital, Harvard Medical School, Boston, MA) JoAnn Manson; (Brown University, Providence, RI) Annlouise R Assaf; (Emory University, Atlanta, GA) Lawrence Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA) Shirley Beresford; (George Washington University Medical Center, Washington, DC) Judith Hsia; (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR) Evelyn Whitlock; (Kaiser Permanente Division of Research, Oakland, CA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC) Barbara V Howard; (Northwestern University, Chicago/Evanston, IL) Linda Van Horn; (Rush Medical Center, Chicago, IL) Henry Black; (Stanford Prevention Research Center, Stanford, CA) Marcia L Stefanick; (State University of New York at Stony Brook, Stony Brook, NY) Dorothy Lane; (The Ohio State University, Columbus, OH) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL) Cora E Lewis; (University of Arizona, Tucson/Phoenix, AZ) Tamsen Bassford; (University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA) John Robbins; (University of California at Irvine, CA) F Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA) Howard Judd; (University of California at San Diego, LaJolla/Chula Vista, CA) Robert D Langer; (University of Cincinnati, Cincinnati, OH) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University of Hawaii, Honolulu, HI) David Curb; (University of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ) Norman Lasser; (University of Miami, Miami, FL) Mary Jo O'Sullivan; (University of Minnesota, Minneapolis, MN) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA) Lewis Kuller; (University of Tennessee, Memphis, TN) Karen C Johnson; (University of Texas Health Science Center, San Antonio, TX) Robert Brzyski; (University of Wisconsin, Madison, WI) Gloria E Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC) Denise Bonds; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI) Susan Hendrix. NR 47 TC 30 Z9 31 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2010 VL 2 AR 48 DI 10.1186/gm169 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA V27QG UT WOS:000208627100048 PM 20667078 ER PT J AU Rotimi, CN Marshall, PA AF Rotimi, Charles N. Marshall, Patricia A. TI Tailoring the process of informed consent in genetic and genomic research SO GENOME MEDICINE LA English DT Article AB Genomic science and associated technologies are facilitating an unprecedented rate of discovery of novel insights into the relationship between human genetic variation and health. The willingness of large numbers of individuals from different ethnic and cultural backgrounds to donate biological samples is one of the major factors behind the success of the ongoing genomic revolution. Although current informed consent documents and processes demonstrate a commitment to ensuring that study participants are well informed of the risks and benefits of participating in genomic studies, there continues to be a need to develop effective new approaches for adequately informing participants of the changing complexities of the scientific and ethical issues that arise in the conduct of genomics research. Examples of these complexities in genomic research include more widespread use of whole-genome sequencing technologies, broad sharing of individual-level data, evolving information technology, the growing demand for the return of genetic results to participants, and changing attitudes about privacy and the expansion of genomics studies to global populations representing diverse cultural, linguistic and socio-economic backgrounds. We highlight and briefly discuss the importance of ten core scientific, cultural and social factors that are particularly relevant to tailoring informed consent in genomic research, and we draw attention to the need for the informed consent document and process to be responsive to the evolving nature of genomic research. C1 [Rotimi, Charles N.] NHGRI, Inherited Dis Res Branch, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. RP Rotimi, CN (reprint author), NHGRI, Inherited Dis Res Branch, Ctr Res Genom & Global Hlth, NIH, 12 South Dr, Bethesda, MD 20892 USA. EM rotimic@mail.nih.gov; patricia.marshall@case.edu FU Center for Research on Genomics and Global Health, NHGRI/NIH; Center for Genetic Research Ethics and Law [3P50-HG003390]; NIH [1RC1HG005789 -NHGRI, UL1 RR024989 -NCRR] FX We are grateful for the technical support of Deborah Hawkins. The preparation of this manuscript was supported by funds from the Center for Research on Genomics and Global Health, NHGRI/NIH; at Case Western Reserve University by the Center for Genetic Research Ethics and Law (3P50-HG003390), and the following NIH grants 1RC1HG005789 -NHGRI; UL1 RR024989 -NCRR. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH. NR 48 TC 29 Z9 31 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2010 VL 2 AR 20 DI 10.1186/gm141 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA V27QG UT WOS:000208627100020 PM 20346094 ER PT J AU Sarachana, T Zhou, RL Chen, G Manji, HK Hu, VW AF Sarachana, Tewarit Zhou, Rulun Chen, Guang Manji, Husseini K. Hu, Valerie W. TI Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines SO GENOME MEDICINE LA English DT Article AB Background: Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by abnormalities in reciprocal social interactions and language development and/or usage, and by restricted interests and repetitive behaviors. Differential gene expression of neurologically relevant genes in lymphoblastoid cell lines from monozygotic twins discordant in diagnosis or severity of autism suggested that epigenetic factors such as DNA methylation or microRNAs (miRNAs) may be involved in ASD. Methods: Global miRNA expression profiling using lymphoblasts derived from these autistic twins and unaffected sibling controls was therefore performed using high-throughput miRNA microarray analysis. Selected differentially expressed miRNAs were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis, and the putative target genes of two of the confirmed miRNA were validated by knockdown and overexpression of the respective miRNAs. Results: Differentially expressed miRNAs were found to target genes highly involved in neurological functions and disorders in addition to genes involved in gastrointestinal diseases, circadian rhythm signaling, as well as steroid hormone metabolism and receptor signaling. Novel network analyses of the putative target genes that were inversely expressed relative to the relevant miRNA in these same samples further revealed an association with ASD and other co-morbid disorders, including muscle and gastrointestinal diseases, as well as with biological functions implicated in ASD, such as memory and synaptic plasticity. Putative gene targets (ID3 and PLK2) of two RT-PCR-confirmed brain-specific miRNAs (hsa-miR-29b and hsa-miR-219-5p) were validated by miRNA overexpression or knockdown assays, respectively. Comparisons of these mRNA and miRNA expression levels between discordant twins and between case-control sib pairs show an inverse relationship, further suggesting that ID3 and PLK2 are in vivo targets of the respective miRNA. Interestingly, the up-regulation of miR-23a and down-regulation of miR-106b in this study reflected miRNA changes previously reported in post-mortem autistic cerebellum by Abu-Elneel et al. in 2008. This finding validates these differentially expressed miRNAs in neurological tissue from a different cohort as well as supports the use of the lymphoblasts as a surrogate to study miRNA expression in ASD. Conclusions: Findings from this study strongly suggest that dysregulation of miRNA expression contributes to the observed alterations in gene expression and, in turn, may lead to the pathophysiological conditions underlying autism. C1 [Sarachana, Tewarit; Hu, Valerie W.] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Zhou, Rulun; Chen, Guang; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Hu, VW (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, 2300 Eye St NW, Washington, DC 20037 USA. EM bcmvwh@gwumc.edu RI Chen, Guang/A-2570-2017; OI Hu, Valerie/0000-0002-3357-0777 FU Autism Speaks [2381]; NIMH [R21 MH073393, 1U24MH081810]; Office of the Commission on Higher Education of the Royal Thai Government, Thailand; National Institute of Mental Health FX We thank Ms Ioline Henter (NIMH) for her help in editing this manuscript. This work was supported by grant #2381 from Autism Speaks (VWH) and in part by NIMH Grant #R21 MH073393 (VWH). TS is supported by a Higher Educational Strategic Scholarship for Frontier Research from the Office of the Commission on Higher Education of the Royal Thai Government, Thailand. TS is a predoctoral student in the Institute for Biomedical Sciences at The George Washington University. This work is part of dissertation research to be presented in partial fulfillment of the requirements for the PhD. We also gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium* and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the National Institute of Mental Health to Clara M Lajonchere (PI). *The AGRE Consortium: Dan Geschwind, MD, PhD, UCLA, Los Angeles, CA; Maja Bucan, PhD, University of Pennsylvania, Philadelphia, PA; W Ted Brown, MD, PhD, FACMG, NYS Institute for Basic Research in Developmental Disabilities, Long Island, NY; Rita M Cantor, PhD, UCLA School of Medicine, Los Angeles, CA; John N Constantino, MD, Washington University School of Medicine, St Louis, MO; T Conrad Gilliam, PhD, University of Chicago, Chicago, IL; Martha Herbert, MD, PhD, Harvard Medical School, Boston, MA; Clara Lajonchere, PhD, Cure Autism Now, Los Angeles, CA; David H Ledbetter, PhD, Emory University, Atlanta, GA; Christa Lese-Martin, PhD, Emory University, Atlanta, GA; Janet Miller, JD, PhD, Cure Autism Now, Los Angeles, CA; Stanley F Nelson, MD, UCLA School of Medicine, Los Angeles, CA; Gerard D Schellenberg, PhD, University of Washington, Seattle, WA; Carol A Samango-Sprouse, EdD, George Washington University, Washington, DC; Sarah Spence, MD, PhD, UCLA, Los Angeles, CA; Matthew State, MD, PhD, Yale University, New Haven, CT; Rudolph E Tanzi, PhD, Massachusetts General Hospital, Boston, MA. NR 142 TC 84 Z9 90 U1 6 U2 29 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2010 VL 2 AR 23 DI 10.1186/gm144 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA V27QG UT WOS:000208627100023 PM 20374639 ER PT J AU Zhao, YD Simon, R AF Zhao, Yingdong Simon, Richard TI Gene expression deconvolution in clinical samples SO GENOME MEDICINE LA English DT Article ID MICROARRAY DATA; CELL-POPULATIONS; PATTERNS; BLOOD AB Cell type heterogeneity may have a substantial effect on gene expression profiling of human tissue. Several in silico methods for deconvoluting a gene expression profile into cell-type-specific subprofiles have been published but not widely used. Here, we consider recent methods and the experimental validations available for them. Shen-Orr et al. recently developed an approach called cell-type-specific significance analysis of microarray for deconvoluting gene expression. This method requires the measurement of the proportion of each cell type in each sample and the expression profiles of the heterogeneous samples. It determines how gene expression varies among pre-defined phenotypes for each cell type. Gene expression can vary substantially among cell types and sample heterogeneity can mask the identification of biologically important phenotypic correlations. Consequently, the deconvolution approach can be useful in the analysis of mixtures of cell populations in clinical samples. C1 [Zhao, Yingdong; Simon, Richard] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. EM rsimon@mail.nih.gov NR 10 TC 17 Z9 17 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2010 VL 2 AR 93 DI 10.1186/gm214 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA V27QG UT WOS:000208627100093 PM 21211069 ER PT J AU Liu, HH Lu, P Guo, YY Farrell, E Zhang, X Zheng, M Bosano, B Zhang, ZM Allard, J Liao, GC Fu, SY Chen, JZ Dolim, K Kuroda, A Usuka, J Cheng, J Tao, W Welch, K Liu, YZ Pease, J de Keczer, SA Masjedizadeh, M Hu, JS Weller, P Garrow, T Peltz, G AF Liu, Hong-Hsing Lu, Peng Guo, Yingying Farrell, Erin Zhang, Xun Zheng, Ming Bosano, Betty Zhang, Zhaomei Allard, John Liao, Guochun Fu, Siyu Chen, Jinzhi Dolim, Kimberly Kuroda, Ayako Usuka, Jonathan Cheng, Janet Tao, William Welch, Kevin Liu, Yanzhou Pease, Joseph de Keczer, Steve A. Masjedizadeh, Mohammad Hu, Jing-Shan Weller, Paul Garrow, Tim Peltz, Gary TI An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity SO GENOME RESEARCH LA English DT Article ID BETAINE-HOMOCYSTEINE METHYLTRANSFERASE; S-METHYLMETHIONINE; HEPATOTOXICITY; INJURY; MICE; RECEPTOR; MOUSE; PROGRESSION; GLUTATHIONE; EXPRESSION AB Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple inbred mouse strains, along with knowledge-based filtering of these data, identified betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that affected susceptibility to acetaminophen-induced liver toxicity in mice. Through an effect on methionine and glutathione biosynthesis, Bhmt2 could utilize its substrate (S-methylmethionine [SMM]) to confer protection against acetaminophen-induced injury in vivo. Since SMM is only synthesized in plants, Bhmt2 exerts its beneficial effect in a diet-dependent manner. Identification of Bhmt2 and the affected biosynthetic pathway demonstrates how a novel method of integrative genomic analysis in mice can provide a unique and clinically applicable approach to a major public health problem. C1 [Liu, Hong-Hsing; Lu, Peng; Guo, Yingying; Farrell, Erin; Zhang, Xun; Zhang, Zhaomei; Allard, John; Liao, Guochun; Fu, Siyu; Chen, Jinzhi; Cheng, Janet; Hu, Jing-Shan] Roche Palo Alto, Dept Genet & Genom, Palo Alto, CA 94304 USA. [Zheng, Ming; Bosano, Betty; Dolim, Kimberly; Kuroda, Ayako; Usuka, Jonathan; Tao, William; Weller, Paul] Roche Palo Alto, Nonclin Safety, Palo Alto, CA 94304 USA. [Welch, Kevin] Roche Palo Alto, Tech Sci, Palo Alto, CA 94304 USA. [Liu, Yanzhou; Pease, Joseph; de Keczer, Steve A.; Masjedizadeh, Mohammad] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Garrow, Tim] Univ Illinois, Dept Food Sci & Nutr, Urbana, IL 61801 USA. [Peltz, Gary] Stanford Univ, Dept Anesthesia, Stanford, CA 94305 USA. RP Liu, HH (reprint author), Roche Palo Alto, Dept Genet & Genom, Palo Alto, CA 94304 USA. EM honghsing.liu@gmail.com OI Liu, Hong-Hsing/0000-0002-3745-7202 FU NIGMS [1 R01 GM068885-01A1]; NIDDK [1 R01 DK52501] FX Y-Y.G., P. L. and E. F. were supported by a grant (1 R01 GM068885-01A1) from the NIGMS awarded to G. P. This work was also supported by a grant (1 R01 DK52501) from the NIDDK awarded to T. A. G. We thank Christopher Smith and Pamela Mclawhon for expert animal care and technical assistance; Alberto Lapresca and Earl Meierhenry for help with analysis of liver tissues; and David Clark, Bob Lewis, Richard Hanson, Lance Pohl, Adrien Fretland, and Kaushik Chakravarty for helpful discussions. NR 47 TC 21 Z9 22 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2010 VL 20 IS 1 BP 28 EP 35 DI 10.1101/gr.097212.109 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 539JF UT WOS:000273249500004 PM 19923254 ER PT S AU Leyk, S Phillips, TP Smith, JM Nuckols, JR AF Leyk, S. Phillips, T. P. Smith, J. M. Nuckols, J. R. GP ISPRS TI DIARRHEAL MORTALITY OF CHILDREN IN ASSOCIATION WITH HYDROGRAPHY IN BRAZIL SO GEOSPATIAL DATA AND GEOVISUALIZATION: ENVIRONMENT, SECURITY, AND SOCIETY SE International Archives of the Photogrammetry Remote Sensing and Spatial Information Sciences LA English DT Proceedings Paper CT Joint Symposium of ISPRS Commission IV / AutoCarto Annual Conference CY NOV 15-19, 2010 CL Orlando, FL SP Int Soc Photogrammetry & Remote Sensing DE Scale; Modelling; Spatial Infrastructures; Temporal; Spatial Epidemiology AB Is the pattern of childhood mortality due to diarrhea related to hydrography? To answer this kind of question we describe a method to examine associations between peak time of mortality from diarrhea in children less than 5 years for the period 1979-89 and relative location along the hydrologic regime of 8 major hydrographic regions in Brazil. In order to better understand the underlying heterogeneity found in mortality peak timing patterns a multiscale approach is used. Continuous geostatistical surfaces of mortality peak timing are created and validated based on these different spatial scales. We extract "mortality peak timing profiles" along the main streams within Brazil and test for possible trends in this peak timing variable in stream flow direction. Some first results demonstrate that there is a dominant trend of increasing mortality peak timing values downstream for most of the hydrographic regions. There are considerable differences between the spatial scales due to the higher degree of heterogeneity in peak timing at finer spatial scales, which remains hidden at coarser spatial scales. We found some deviations in the explored trends, which are possibly caused by a lack of underlying data and thus higher uncertainty in the underlying geostatistical model. Two hydrographic regions even show a trend into the opposite direction, upstream. Our approach allows for the formulation of interesting hypotheses regarding the capture of regional dynamics of diarrheal disease within various hydrographic regions. However, further research and refinement of assumptions is needed to improve this approach. One distinct advantage of the proposed approach is that the results are robust against effects of regional variation and non-linearity of relationships. C1 [Leyk, S.; Nuckols, J. R.] US Natl Inst Hlth, Fogarty Int Ctr Adv Study Hlth Sci, Bethesda, MD 20892 USA. [Leyk, S.; Phillips, T. P.; Smith, J. M.] Univ Colorado, Dept Geog, Boulder, CO 80309 USA. [Phillips, T. P.] Univ Colorado, Dept Aerosp Engn, Colorado Ctr Astrodynam Res, Boulder, CO 80309 USA. [Nuckols, J. R.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. RP Leyk, S (reprint author), US Natl Inst Hlth, Fogarty Int Ctr Adv Study Hlth Sci, Bethesda, MD 20892 USA. EM stefan.leyk@colorado.edu; thomas.phillips@colorado.edu; jmsmith@colorado.edu; john.nuckols@colostate.edu NR 12 TC 0 Z9 0 U1 0 U2 1 PU COPERNICUS GESELLSCHAFT MBH PI GOTTINGEN PA BAHNHOFSALLE 1E, GOTTINGEN, 37081, GERMANY SN 2194-9034 J9 INT ARCH PHOTOGRAMM PY 2010 VL 38 PN 4 PG 7 WC Geography, Physical; Remote Sensing; Imaging Science & Photographic Technology SC Physical Geography; Remote Sensing; Imaging Science & Photographic Technology GA BE1RS UT WOS:000368436900052 ER PT B AU Zhang, CL AF Zhang, Cuilin BE Kim, C Ferrara, A TI Risk Factors for Gestational Diabetes: from an Epidemiological Standpoint SO GESTATIONAL DIABETES DURING AND AFTER PREGNANCY LA English DT Article; Book Chapter ID RECREATIONAL PHYSICAL-ACTIVITY; WHOLE-GRAIN INTAKE; GLUCOSE-TOLERANCE; DIETARY-FAT; INSULIN SENSITIVITY; CIGARETTE-SMOKING; NULLIPAROUS WOMEN; PREGNANT-WOMEN; SHORT STATURE; FIBER INTAKE C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. EM zhangcu@mail.nih.gov NR 82 TC 3 Z9 4 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-84882-119-4 PY 2010 BP 71 EP 81 DI 10.1007/978-1-84882-120-0_5 D2 10.1007/978-1-84882-120-0 PG 11 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA BSX93 UT WOS:000286091900005 ER PT J AU Suzman, R AF Suzman, Richard TI The INDEPTH WHO-SAGE multicentre study on ageing, health and well-being among people aged 50 years and over in eight countries in Africa and Asia SO GLOBAL HEALTH ACTION LA English DT Editorial Material C1 NIA, Div Behav & Social Res, NIH, Bethesda, MD 20892 USA. RP Suzman, R (reprint author), NIA, Div Behav & Social Res, NIH, Bethesda, MD 20892 USA. NR 18 TC 3 Z9 3 U1 0 U2 2 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 1654-9880 J9 GLOBAL HEALTH ACTION JI Glob. Health Action PY 2010 VL 3 SU 2 BP 5 EP 7 DI 10.3402/gha.v3i0.5480 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V20SU UT WOS:000208160500003 ER PT B AU Atlas, J AF Atlas, Jennifer BE Takenaka, A Osirim, MJ TI Healthcare Access for Mexican Immigrants in South Philadelphia SO GLOBAL PHILADELPHIA: IMMIGRANT COMMUNITIES OLD AND NEW SE Philadelphia Voices Philadelphia Visions LA English DT Article; Book Chapter ID SERVICES C1 NIH, Ctr Clin, Michigans Mott Childrens Hlth Ctr, Bethesda, MD 20892 USA. RP Atlas, J (reprint author), NIH, Ctr Clin, Michigans Mott Childrens Hlth Ctr, Bethesda, MD 20892 USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU TEMPLE UNIV PRESS PI PHILADELPHIA PA BROAD & OXFORD ST, PHILADELPHIA, PA 19122 USA BN 978-1-4399-0014-7; 978-1-4399-0013-0 J9 PHILA VOICES PHILA PY 2010 BP 178 EP 196 PG 19 WC Social Sciences, Interdisciplinary; Urban Studies SC Social Sciences - Other Topics; Urban Studies GA BA6MI UT WOS:000337183700010 ER PT S AU Paldy, A Bobvos, J AF Paldy, Anna Bobvos, Janos BE Dincer, I Midilli, A Hepbasli, A Karakoc, TH TI Health Impacts of Heat Waves of 2007 in Hungary - Background and Experiences SO GLOBAL WARMING: ENGINEERING SOLUTIONS SE Green Energy and Technology LA English DT Proceedings Paper CT Global Conference on Global Warming CY JUL 06-10, 2008 CL Istanbul, TURKEY ID MORTALITY C1 [Paldy, Anna; Bobvos, Janos] Natl Inst Environm Hlth, Res Triangle Pk, NC 27709 USA. RP Paldy, A (reprint author), Natl Inst Environm Hlth, Res Triangle Pk, NC 27709 USA. RI Dincer, Ibrahim/A-5379-2012 NR 29 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1865-3529 BN 978-1-4419-1016-5 J9 GREEN ENERGY TECHNOL PY 2010 BP 629 EP 642 DI 10.1007/978-1-4419-1017-2_44 PG 14 WC Engineering, Mechanical SC Engineering GA BRE21 UT WOS:000282475000044 ER PT B AU Skolnick, P Popik, P Trullas, R AF Skolnick, Phil Popik, Piotr Trullas, Ramon BE Skolnick, P TI N-Methyl-D-Aspartate (NMDA) Antagonists for the Treatment of Depression SO GLUTAMATE-BASED THERAPIES FOR PSYCHIATRIC DISORDERS SE Milestones in Drug Therapy LA English DT Article; Book Chapter ID SEROTONIN REUPTAKE INHIBITORS; LONG-TERM POTENTIATION; RAT FRONTAL-CORTEX; FORCED SWIMMING TEST; MILD STRESS MODEL; NEUROTROPHIC FACTOR; RECEPTOR ANTAGONIST; CLINICAL-TRIALS; ANTIDEPRESSANT TREATMENTS; LEARNED HELPLESSNESS AB Depression is a major public health concern that affects similar to 5% of the population in industrialized societies in any given year. Drugs that increase the synaptic availability of biogenic amines (norepinephrine, serotonin, and/or dopamine) have been used to treat depression for over five decades. While the most widely used antidepressants (serotonin and/or norepinephrine selective reuptake inhibitors) are generally safe and effective for many individuals, these drugs are far from ideal. For example, controlled clinical studies have repeatedly demonstrated that >= 2-4 weeks of treatment are required to provide palpable symptom relief. In addition, between 30 and 40% of patients do not respond to a first course of therapy with these biogenic amine-based agents. By contrast, N-methyl-D-aspartate (NMDA) receptor antagonists have been reported to produce rapid and robust antidepressant effects in patients unresponsive to conventional antidepressants. The use of these agents as antidepressants is grounded on a corpus of preclinical evidence, first published 20 years ago, demonstrating the antidepressant-like properties of NMDA antagonists and that chronic treatment with conventional antidepressants attenuates NMDA receptor function. In this chapter, we describe evidence that NMDA antagonists represent an effective alternative to biogenic amine-based agents for treating depression and provide perspective on the hurdles that could impede the development and commercialization of these agents in the face of this remarkable clinical data. C1 [Skolnick, Phil] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. [Popik, Piotr] Polish Acad Sci, Inst Pharmacol, PL-31343 Krakow, Poland. [Popik, Piotr] Jagiellonian Univ, Coll Med, Fac Publ Hlth, Krakow, Poland. [Trullas, Ramon] Inst Invest Biomed August Pi & Sunyer, CSIC, Inst Invest Biomed Barcelona, Neurobiol Unit, Barcelona 08036, Spain. [Trullas, Ramon] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain. RP Skolnick, P (reprint author), Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM Phil.Skolnick@nih.gov; Phil.Skolnick@nih.gov RI Popik, Piotr/R-5383-2016; Trullas, Ramon/D-2197-2016 OI Popik, Piotr/0000-0003-0722-1263; Trullas, Ramon/0000-0001-7951-9881 NR 103 TC 3 Z9 3 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 978-3-0346-0240-2 J9 MILESTONES DRUG THER JI Milest. Drug Ther. PY 2010 BP 1 EP 20 DI 10.1007/978-3-0346-0241-9_1 D2 10.1007/978-3-0346-0241-9 PG 20 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA BRF26 UT WOS:000282600900001 ER PT J AU Bongat, AFG Saksena, R Adamo, R Fujimoto, Y Shiokawa, Z Peterson, DC Fukase, K Vann, WF Kovac, P AF Bongat, Aileen F. G. Saksena, Rina Adamo, Roberto Fujimoto, Yukari Shiokawa, Zenyu Peterson, Dwight C. Fukase, Koichi Vann, Willie F. Kovac, Pavol TI Multimeric bivalent immunogens from recombinant tetanus toxin H-C fragment, synthetic hexasaccharides, and a glycopeptide adjuvant SO GLYCOCONJUGATE JOURNAL LA English DT Article DE Conjugate vaccine; Vibrio cholerae; Adjuvant; Squaric acid; Tetanus toxin C fragment ID VIBRIO-CHOLERAE O-1; SQUARIC ACID DIESTER; SEROTYPE OGAWA; PROTEIN CARRIER; ESCHERICHIA-COLI; C-13-NMR SPECTRA; DIETHYL SQUARATE; IMMUNE-RESPONSE; O-PS; GANGLIOSIDE AB Using recombinant tetanus toxin H-C fragment (rTT-H-C) as carrier, we prepared multimeric bivalent immunogens featuring the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Ogawa, in combination with either the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Inaba, or a synthetic disaccharide tetrapeptide peptidoglycan fragment as adjuvant. The conjugation reaction was effected by squaric acid chemistry and monitored in virtually real time by SELDI-TOF MS. In this way, we could prepare well-defined immunogens with predictable carbohydrate-carrier ratio, whose molecular mass and the amount of each saccharide attached could be independently determined. The ability to prepare such neoglycoconjugates opens unprecedented possibilities for preparation of conjugate vaccines for bacterial diseases from synthetic carbohydrates. C1 [Bongat, Aileen F. G.; Adamo, Roberto; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA. [Fujimoto, Yukari; Shiokawa, Zenyu; Fukase, Koichi] Osaka Univ, Dept Chem, Grad Sch Sci, Osaka 5600043, Japan. [Saksena, Rina; Peterson, Dwight C.; Vann, Willie F.] US FDA, OVRR, CBER, Lab Bacterial Toxins, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, LBC, NIH, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov RI Kovac, Pavol/B-8813-2008; Fujimoto, Yukari/M-7282-2014 OI Kovac, Pavol/0000-0001-5044-3449; Fujimoto, Yukari/0000-0001-5320-3192 FU NIH, NIDDK FX This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 51 TC 10 Z9 10 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD JAN PY 2010 VL 27 IS 1 BP 69 EP 77 DI 10.1007/s10719-009-9259-4 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 549HC UT WOS:000274037100007 PM 19757026 ER PT S AU Du, YB Xie, W Liu, CY AF Du, Yubin Xie, Wen Liu, Chengyu BE Wassarman, PM Soriano, PM TI STRATEGIES AND CONSIDERATIONS FOR DISTRIBUTING AND RECOVERING MOUSE LINES SO GUIDE TO TECHNIQUES IN MOUSE DEVELOPMENT, PT A: MICE, EMBRYOS, AND CELLS, 2ND EDITION SE Methods in Enzymology LA English DT Review; Book Chapter ID CRYOPRESERVED MOUSE; IN-VITRO; SPERM INJECTION; OVARIAN TISSUE; SPERMATOZOA; FROZEN; MICE; TRANSPLANTATION; FERTILIZATION; EMBRYOS AB As more and more genetically modified mouse lines are being generated, it becomes increasingly common to share animal models among different research institutions. Live mice are routinely transferred between animal facilities. Due to various issues concerning animal welfare, intellectual property rights, colony health status and biohazard, significant paperwork and coordination are required before any animal travel can take place. Shipping fresh or frozen preimplantation embryos, gametes, or reproductive organs can bypass some of the issues associated with live animal transfer, but it requires the receiving facilities to be able to perform delicate and sometimes intricate procedures such as embryo transfer, in vitro fertilization (IVF), or ovary transplantation. Here, we summarize the general requirements for live animal transport and review some of the assisted reproductive technologies (ART) that can be applied to shipping and reviving mouse lines. Intended users of these methods should consult their institution's responsible official to find out whether each specific method is legal or appropriate in their own animal facilities. C1 [Du, Yubin; Xie, Wen; Liu, Chengyu] NHLBI, Transgen Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Du, YB (reprint author), NHLBI, Transgen Core Facil, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIC HL005907-03, Z99 HL999999, ZIC HL005907-02, ZIC HL005907-04] NR 45 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-08-088778-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 476 BP 37 EP 52 DI 10.1016/S0076-6879(10)76003-1 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFW38 UT WOS:000321623500004 PM 20691859 ER PT S AU Takahashi, H Liu, CY AF Takahashi, Hideko Liu, Chengyu BE Wassarman, PM Soriano, PM TI ARCHIVING AND DISTRIBUTING MOUSE LINES BY SPERM CRYOPRESERVATION, IVF, AND EMBRYO TRANSFER SO GUIDE TO TECHNIQUES IN MOUSE DEVELOPMENT, PT A: MICE, EMBRYOS, AND CELLS, 2ND EDITION SE Methods in Enzymology LA English DT Review; Book Chapter ID IN-VITRO FERTILIZATION; TRANSGENIC MOUSE; ZONA-PELLUCIDA; SPERMATOZOA; EFFICIENT; SURVIVAL; STRAINS; OOCYTES; FROZEN; MICE AB The number of genetically modified mouse lines has been increasing exponentially in the past few decades. In order to safeguard them from accidental loss and genetic drifting, to reduce animal housing cost, and to efficiently distribute them around the world, it is important to cryopreserve these valuable genetic resources. Preimplantation-stage embryos from thousands of mouse lines have been cryopreserved during the past two to three decades. Although reliable, this method requires several hundreds of embryos, which demands a sizable breeding colony, to safely preserve each line. This requirement imposes significant delay and financial burden for the archiving effort. Sperm cryopreservation is now emerging as the leading method for storing and distributing mouse lines, largely due to the recent finding that addition of a reducing agent, monothioglycerol, into the cryoprotectant can significantly increase the in vitro fertilization (IVF) rate in many mouse strains, including the most widely used C57BL/6 strain. This method is quick, inexpensive, and requires only two breeding age male mice, but it still remains tricky and strain-dependent. A small change in experimental conditions can lead to significant variations in the outcome. In this chapter, we describe in detail our sperm cryopreservation, IVF, and oviduct transfer procedures for storing and reviving genetically modified mouse lines. C1 [Takahashi, Hideko] NEI, Vet Res & Resource Sect, NIH, Bethesda, MD 20892 USA. [Takahashi, Hideko] NEI, Genet Engn Facil, NIH, Bethesda, MD 20892 USA. [Liu, Chengyu] NHLBI, Transgen Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Takahashi, H (reprint author), NEI, Vet Res & Resource Sect, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HL999999, ZIC HL005907-02, ZIC HL005907-03, ZIC HL005907-04] NR 23 TC 5 Z9 5 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 978-0-08-088778-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2010 VL 476 BP 53 EP 69 DI 10.1016/S0076-6879(10)76004-3 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFW38 UT WOS:000321623500005 PM 20691860 ER PT S AU Gerfen, CR Bolam, JP AF Gerfen, Charles R. Bolam, J. Paul BE Steiner, H Tseng, KY TI The Neuroanatomical Organization of the Basal Ganglia SO HANDBOOK OF BASAL GANGLIA STRUCTURE AND FUNCTION SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter ID RAT GLOBUS-PALLIDUS; ELECTRON-MICROSCOPIC ANALYSIS; DOPAMINE-RECEPTOR GENE; NIGRA PARS RETICULATA; IDENTIFIED STRIATONIGRAL NEURONS; VITRO SLICE PREPARATION; CENTRAL-NERVOUS-SYSTEM; LEUKOAGGLUTININ PHA-L; GABA-CONTAINING INPUT; SUBSTANTIA-NIGRA C1 [Gerfen, Charles R.] NIMH, Lab Syst Neurosci, Dickerson, MD USA. [Bolam, J. Paul] Univ Oxford, MRC Anat Neuropharmacol Unit, Oxford, England. RP Gerfen, CR (reprint author), NIMH, Lab Syst Neurosci, Dickerson, MD USA. NR 171 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-091215-8 J9 HBK BEHAV NEUROSCI PY 2010 VL 20 BP 3 EP 28 PG 26 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BCT44 UT WOS:000311354500002 ER PT S AU Plenz, D Wickens, JR AF Plenz, Dietmar Wickens, Jeffery R. BE Steiner, H Tseng, KY TI The Striatal Skeleton: Medium Spiny Projection Neurons and their Lateral Connections SO HANDBOOK OF BASAL GANGLIA STRUCTURE AND FUNCTION SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter ID RAT NEOSTRIATAL NEURONS; MEMBRANE-POTENTIAL FLUCTUATIONS; NUCLEUS ACCUMBENS NEURONS; LONG-TERM POTENTIATION; GATED SODIUM CURRENT; WINNER-TAKE-ALL; IN-VIVO; BASAL GANGLIA; SYNAPTIC PLASTICITY; RECEPTOR ACTIVATION C1 [Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Lab Syst Neurosci, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Wickens, Jeffery R.] Okinawa Inst Sci & Technol, Neurobiol Res Unit, Uruma City, Okinawa, Japan. RP Plenz, D (reprint author), NIMH, Sect Crit Brain Dynam, Lab Syst Neurosci, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. NR 137 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-091215-8 J9 HBK BEHAV NEUROSCI PY 2010 VL 20 BP 99 EP 112 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BCT44 UT WOS:000311354500006 ER PT S AU Lovinger, DM Davis, MI Costa, RM AF Lovinger, David M. Davis, Margaret I. Costa, Rui M. BE Steiner, H Tseng, KY TI Endocannabinoid Signaling in the Striatum SO HANDBOOK OF BASAL GANGLIA STRUCTURE AND FUNCTION SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter ID LONG-TERM DEPRESSION; CB1 CANNABINOID RECEPTOR; VENTRAL TEGMENTAL AREA; CENTRAL-NERVOUS-SYSTEM; DOPAMINE D2 RECEPTORS; ACID AMIDE HYDROLASE; DEPOLARIZATION-INDUCED SUPPRESSION; RAT DORSOLATERAL STRIATUM; MEDIAL PREFRONTAL CORTEX; MESSENGER-RNA EXPRESSION C1 [Lovinger, David M.; Davis, Margaret I.; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, Bethesda, MD USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Bethesda, MD USA. OI Davis, Margaret/0000-0002-0489-8351 NR 176 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-091215-8 J9 HBK BEHAV NEUROSCI PY 2010 VL 20 BP 167 EP 186 PG 20 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BCT44 UT WOS:000311354500010 ER PT S AU Walters, JR Bergstrom, DA AF Walters, Judith R. Bergstrom, Debra A. BE Steiner, H Tseng, KY TI Synchronous Activity in Basal Ganglia Circuits SO HANDBOOK OF BASAL GANGLIA STRUCTURE AND FUNCTION SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter ID NIGRA PARS RETICULATA; DOPAMINE-RECEPTOR STIMULATION; ADVANCED PARKINSONS-DISEASE; DEEP-BRAIN-STIMULATION; LOCAL-FIELD POTENTIALS; HUMAN SUBTHALAMIC NUCLEUS; EXTERNAL GLOBUS-PALLIDUS; DEVELOPING NEURAL CIRCUITS; SLOW OSCILLATORY ACTIVITY; MOVEMENT-RELATED CHANGES C1 [Walters, Judith R.; Bergstrom, Debra A.] NINDS, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Walters, JR (reprint author), NINDS, Neurophysiol Pharmacol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 174 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-091215-8 J9 HBK BEHAV NEUROSCI PY 2010 VL 20 BP 429 EP 443 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BCT44 UT WOS:000311354500026 ER PT S AU Gerfen, CR AF Gerfen, Charles R. BE Steiner, H Tseng, KY TI D1 Dopamine Receptor Supersensitivity in the Dopamine-Depleted Striatum: Aberrant ERK1/2 Signaling SO HANDBOOK OF BASAL GANGLIA STRUCTURE AND FUNCTION SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter ID GENE-EXPRESSION; C-FOS; INDUCED DYSKINESIA; PARKINSONS-DISEASE; VENTRAL STRIATUM; MATRIX COMPARTMENTS; REGULATED KINASE; NMDA RECEPTORS; MESSENGER-RNAS; RAT FOREBRAIN C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Gerfen, CR (reprint author), NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. NR 37 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-091215-8 J9 HBK BEHAV NEUROSCI PY 2010 VL 20 BP 491 EP 500 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BCT44 UT WOS:000311354500029 ER PT S AU Guha, R AF Guha, Rajarshi BE Faulon, JL Bender, A TI Open Source Chemoinformatics Software and Database Technologies SO HANDBOOK OF CHEMOINFORMATICS ALGORITHMS SE Chapman & Hall CRC Mathematical and Computational Biology Series LA English DT Article; Book Chapter ID DEVELOPMENT KIT CDK; SOURCE JAVA LIBRARY; SURFACE-AREA; DESCRIPTORS; CHEMISTRY; SEARCH; INDEX; BIOINFORMATICS; INFORMATION; PREDICTION C1 NIH Chem Genom Ctr, Rockville, MD USA. RP Guha, R (reprint author), NIH Chem Genom Ctr, Rockville, MD USA. NR 48 TC 0 Z9 0 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-8064 BN 978-1-4200-8299-9 J9 CH CRC MATH COMP BIO JI Math. Comp. Biol. Ser. PY 2010 BP 343 EP 362 D2 10.1201/9781420082999 PG 20 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA BTB69 UT WOS:000286379300013 ER PT S AU Fanos, J Wiener, L Brennan, T AF Fanos, Joanna Wiener, Lori Brennan, Tara BE Tercyak, KP TI Potential Impact of Genomic Information on Childhood Sibling Relationships SO HANDBOOK OF GENOMICS AND THE FAMILY: PSYCHOSOCIAL CONTEXT FOR CHILDREN AND ADOLESCENTS SE Issues in Clinical Child Psychology LA English DT Article; Book Chapter ID SEVERE COMBINED IMMUNODEFICIENCY; ATAXIA-TELANGIECTASIA GENE; INTERLEUKIN-2-RECEPTOR GAMMA-CHAIN; STEM-CELL DONOR; CYSTIC-FIBROSIS; LINKAGE ANALYSIS; CHRONIC ILLNESS; CARRIER STATUS; CHILDREN; CANCER C1 [Fanos, Joanna] Dartmouth Med Sch, Lebanon, NH USA. [Wiener, Lori] NIH, Bethesda, MD 20892 USA. [Brennan, Tara] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Fanos, J (reprint author), Dartmouth Med Sch, Lebanon, NH USA. NR 95 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1574-0471 BN 978-1-4419-5799-3 J9 ISSUES CLIN CHILD PS PY 2010 BP 141 EP 161 DI 10.1007/978-1-4419-5800-6_6 D2 10.1007/978-1-4419-5800-6 PG 21 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA BQD65 UT WOS:000280742700006 ER PT S AU See, T Tifft, CJ AF See, Tricia Tifft, Cynthia J. BE Tercyak, KP TI Single Gene Disease Risk SO HANDBOOK OF GENOMICS AND THE FAMILY: PSYCHOSOCIAL CONTEXT FOR CHILDREN AND ADOLESCENTS SE Issues in Clinical Child Psychology LA English DT Article; Book Chapter ID FRAGILE-X-SYNDROME; DUCHENNE MUSCULAR-DYSTROPHY; QUALITY-OF-LIFE; EARLY-TREATED PHENYLKETONURIA; CYSTIC-FIBROSIS; FOLLOW-UP; SOCIAL-ADJUSTMENT; MEDICAL HOME; CHILDREN; ADOLESCENTS C1 [See, Tricia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tifft, Cynthia J.] NIH, Bethesda, MD 20892 USA. RP See, T (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 76 TC 0 Z9 0 U1 2 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1574-0471 BN 978-1-4419-5799-3 J9 ISSUES CLIN CHILD PS PY 2010 BP 241 EP 266 DI 10.1007/978-1-4419-5800-6_10 D2 10.1007/978-1-4419-5800-6 PG 26 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA BQD65 UT WOS:000280742700010 ER PT S AU Koehly, LM Mcbride, CM AF Koehly, Laura M. McBride, Colleen M. BE Tercyak, KP TI Genomic Risk Information for Common Health Conditions: Maximizing Kinship-Based Health Promotion SO HANDBOOK OF GENOMICS AND THE FAMILY: PSYCHOSOCIAL CONTEXT FOR CHILDREN AND ADOLESCENTS SE Issues in Clinical Child Psychology LA English DT Article; Book Chapter ID NONPOLYPOSIS COLORECTAL-CANCER; BEHAVIOR-CHANGE RESEARCH; BRCA MUTATION CARRIERS; LARGE SOCIAL NETWORK; FAMILY-HISTORY; WIDE ASSOCIATION; OVARIAN-CANCER; LIFE-STYLE; PROPHYLACTIC SURGERY; HEREDITARY BREAST C1 [Koehly, Laura M.; McBride, Colleen M.] NIH, Bethesda, MD 20892 USA. RP Koehly, LM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 122 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1574-0471 BN 978-1-4419-5799-3 J9 ISSUES CLIN CHILD PS PY 2010 BP 407 EP 433 DI 10.1007/978-1-4419-5800-6_17 D2 10.1007/978-1-4419-5800-6 PG 27 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA BQD65 UT WOS:000280742700017 ER PT S AU Hadley, DW Ersig, ADL Quattrocchi, MKH AF Hadley, Donald W. Ersig, Anne D. Letocha Quattrocchi, M. K. Holohan BE Tercyak, KP TI Guidelines and Policies on Genetic Testing in Children and Families SO HANDBOOK OF GENOMICS AND THE FAMILY: PSYCHOSOCIAL CONTEXT FOR CHILDREN AND ADOLESCENTS SE Issues in Clinical Child Psychology LA English DT Article; Book Chapter ID ADULT-ONSET CONDITIONS; COLORECTAL-CANCER; YOUNG-PEOPLE; ATTITUDES; MINORS; SUSCEPTIBILITY; ADOLESCENTS; GENOMICS; DISEASE; ETHICS C1 [Hadley, Donald W.; Ersig, Anne D. Letocha; Quattrocchi, M. K. Holohan] NIH, Bethesda, MD 20892 USA. RP Hadley, DW (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 40 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1574-0471 BN 978-1-4419-5799-3 J9 ISSUES CLIN CHILD PS PY 2010 BP 523 EP 557 DI 10.1007/978-1-4419-5800-6_21 D2 10.1007/978-1-4419-5800-6 PG 35 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA BQD65 UT WOS:000280742700021 ER PT S AU Newman, JD AF Newman, John D. BE Brudzynski, SM TI Evolution of the communication brain in control of mammalian vocalization SO HANDBOOK OF MAMMALIAN VOCALIZATION: AN INTEGRATIVE NEUROSCIENCE APPROACH SE Handbook of Behavioral Neuroscience LA English DT Article; Book Chapter DE evolution of vocal system; limbic system; cingulate gyrus; brainstem; periaqueductal gray ID SQUIRREL-MONKEY; PERIAQUEDUCTAL GRAY; NEURONAL-ACTIVITY; TELEOST FISH; AREA; PHONATION; LARYNGEAL; REPRESENTATION; STIMULATION; MECHANISMS AB The evolution of the brain structures mediating vocal production in mammals is outlined. The structures together form a system. Central to this system is an ancient core that is found in all vertebrates. Mammals have added components in the cerebral cortex, consisting of a limbic midline cortex, as well as neocortical areas that influence laryngeal movement. Together, the elements of this system regulate the broad functional categories of vocalizations, along with the subtle nuances that reflect variation in motivational state, social context, and developmental status of the vocalizer. Despite the great variety of acoustic qualities and species differences found in mammalian vocalizations, the brain pathways and circuits regulating their expression appear to have changed very little over the course of evolution. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Unit Dev Neuroethol, Poolesville, MD USA. RP Newman, JD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Unit Dev Neuroethol, Poolesville, MD USA. EM jdnewman@helix.nih.gov NR 40 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-7339 BN 978-0-08-092337-6 J9 HBK BEHAV NEUROSCI PY 2010 VL 19 BP 23 EP 28 DI 10.1016/B978-0-12-374593-4.00003-6 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BCQ76 UT WOS:000311040500004 ER PT B AU Gail, MH Chatterjee, N AF Gail, Mitchell H. Chatterjee, Nilanjan BE Lin, S Zhao, H TI Estimating the Absolute Risk of Disease Associated with Identified Mutations SO HANDBOOK ON ANALYZING HUMAN GENETIC DATA: COMPUTATIONAL APPROACHES AND SOFTWARE LA English DT Article; Book Chapter ID AUTOSOMAL-DOMINANT MUTATION; CASE-CONTROL FAMILY; BREAST-CANCER; KIN-COHORT; ESTIMATING PENETRANCE; CUMULATIVE RISK; AGGREGATION; DESIGNS; MODELS; BRCA2 AB For a given mutation status, we define the absolute risk as the chance that disease develops in a defined age interval, given that the person is well at the beginning of the interval. Absolute risk is reduced by competing risks of mortality, that may cause the person to die before the disease of interest develops. We distinguish absolute risk from the pure cumulative risk of disease that is often estimated in the genetic epidemiologic literature, and we concentrate on estimating marginal risks for members selected at random from the population, rather than family specific risks. We review cohort, population-based case-control, case-control family, and kin-cohort designs for estimating absolute and pure cumulative risks associated with a measurable genetic mutation. C1 [Gail, Mitchell H.; Chatterjee, Nilanjan] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. RP Gail, MH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. EM gailm@mail.nih.gov NR 34 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-69263-8 PY 2010 BP 289 EP 305 DI 10.1007/978-3-540-69264-5_10 PG 17 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA BMT43 UT WOS:000273538700010 ER PT J AU Skeath, P Fine, AH Berger, A AF Skeath, Perry Fine, Aubrey H. Berger, Ann BE Fine, AH TI Increasing the effectiveness of palliative care through integrative modalities: conceptualizing the roles of animal companions and animal-assisted interventions SO HANDBOOK ON ANIMAL-ASSISTED THERAPY: THEORETICAL FOUNDATIONS AND GUIDELINES FOR PRACTICE, 3RD EDITION LA English DT Article; Book Chapter ID DEPRESSION SCREENING SCALE; POSTPARTUM DEPRESSION; STRESS; EXPERIENCE; INVENTORY; CANCER; STATES C1 [Skeath, Perry; Berger, Ann] NIH, Bethesda, MD 20892 USA. [Fine, Aubrey H.] Calif State Polytech Univ Pomona, Pomona, CA 91768 USA. RP Skeath, P (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 49 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-381454-8 PY 2010 BP 301 EP 327 DI 10.1016/B978-0-12-381453-1.10016-9 PG 27 WC Psychology, Clinical SC Psychology GA BFB52 UT WOS:000319114500018 ER PT J AU Kirkpatrick, B Bean, JA Fleming, LE Kirkpatrick, G Grief, L Nierenberg, K Reich, A Watkins, S Naar, J AF Kirkpatrick, Barbara Bean, Judy A. Fleming, Lora E. Kirkpatrick, Gary Grief, Lynne Nierenberg, Kate Reich, Andrew Watkins, Sharon Naar, Jerome TI Gastrointestinal emergency room admissions and Florida red tide blooms SO HARMFUL ALGAE LA English DT Article DE Gastrointestinal illness; Gastroenteritis; NSP; Neurotoxic shellfish poisoning; Respiratory illness; Asthma; Brevetoxins; Harmful algal blooms (HABs); Karenia brevis ID TOXINS BREVETOXINS; SHELLFISH; ASTHMA AB Human exposure to brevetoxins during Florida red tide blooms formed by Karenia brevis has been documented to cause acute gastrointestinal, neurologic, and respiratory health effects. Traditionally, the routes of brevetoxin exposure have been through the consumption of contaminated bivalve shellfish and the inhalation of contaminated aerosols. However, recent studies using more sensitive methods have demonstrated the presence of brevetoxins in many components of the aquatic food web which may indicate potential alternative routes for human exposure. This study examined whether the presence of a Florida red tide bloom affected the rates of admission for a gastrointestinal diagnosis to a hospital emergency room in Sarasota, FL. The rates of gastrointestinal diagnoses admissions were compared for a 3-month time period in 2001 when Florida red tide bloom was present onshore to the same 3-month period in 2002 when no Florida red tide bloom occurred. A significant 40% increase in the total number of gastrointestinal emergency room admissions for the Florida red tide bloom period was found compared to the non-red tide period. These results suggest that the healthcare community may experience a significant and unrecognized impact from patients needing emergency medical care for gastrointestinal illnesses during Florida red tide blooms. Thus, additional studies characterizing the potential sources of exposure to the toxins, as well as the dose/effect relationship of brevetoxin exposure, should be undertaken. (C) 2009 Elsevier B.V. All rights reserved. C1 [Fleming, Lora E.] Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Kirkpatrick, Barbara; Kirkpatrick, Gary; Nierenberg, Kate] Mote Marine Lab, Sarasota, FL 34236 USA. [Bean, Judy A.] Childrens Hosp, Med Ctr, Cincinnati, OH 45204 USA. [Bean, Judy A.] Univ Cincinnati, Cincinnati, OH 04524 USA. [Fleming, Lora E.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF & NIEHS Oceans & Human Hlth Ctr, Miami, FL 33149 USA. [Fleming, Lora E.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. [Grief, Lynne] Sarasota Mem Hosp, Sarasota, FL 34239 USA. [Reich, Andrew; Watkins, Sharon] Florida Dept Hlth, Tallahassee, FL 32399 USA. [Naar, Jerome] Univ N Carolina, Ctr Marine Sci, Wilmington, NC 28409 USA. RP Fleming, LE (reprint author), Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, 1120 NW 14th Ave,Clin Res Bldg,Room 1049 R 669, Miami, FL 33136 USA. EM lfleming@med.miami.edu FU NOAA Ocean and Human Health Initiative Program [NA05NOS4781246]; Centers for Disease Control and Prevention; Florida Department of Health [U50/CCU423360-02]; National Institute for Environmental Health Sciences (NIEHS) [PO1 ES 10594, 1 P50 ES12736]; Florida Dept of Environmental Protection (FLDEP); National Science Foundation (NSF) [OCE0432368] FX The authors thank Decision Support Services and the Institutional Review Board at Sarasota Memorial Hospital for their outstanding support of this project.[SS] NR 21 TC 8 Z9 8 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD JAN PY 2010 VL 9 IS 1 BP 82 EP 86 DI 10.1016/j.hal.2009.08.005 PG 5 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 530OP UT WOS:000272602500010 PM 20161425 ER PT J AU Ulrich, CM Hamric, AB Grady, C AF Ulrich, Connie M. Hamric, Ann B. Grady, Christine TI Moral Distress: A Growing Problem in the Health Professions? SO HASTINGS CENTER REPORT LA English DT Article C1 [Ulrich, Connie M.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Hamric, Ann B.] Univ Virginia, Sch Nursing, Charlottesville, VA 22903 USA. [Hamric, Ann B.] Univ Virginia, Ctr Biomed Eth & Humanities, Charlottesville, VA 22903 USA. [Hamric, Ann B.] UVA Med Ctr, Moral Distress Consultat Serv, Charlottesville, VA 22903 USA. [Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Ulrich, CM (reprint author), Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NR 10 TC 24 Z9 24 U1 0 U2 7 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN-FEB PY 2010 VL 40 IS 1 BP 20 EP 22 PG 3 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 549ZX UT WOS:000274096100011 PM 20166512 ER PT J AU Millum, J AF Millum, Joseph TI HOW SHOULD THE BENEFITS OF BIOPROSPECTING BE SHARED? SO HASTINGS CENTER REPORT LA English DT Article ID BIODIVERSITY C1 [Millum, Joseph] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Millum, Joseph] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Millum, J (reprint author), NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 26 TC 4 Z9 4 U1 0 U2 11 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN-FEB PY 2010 VL 40 IS 1 BP 24 EP 33 PG 10 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 549ZX UT WOS:000274096100013 PM 20169653 ER PT J AU Duffy, SQ AF Duffy, Sarah Q. TI The Therapeutic Value Of Addiction Treatment Fees SO HEALTH AFFAIRS LA English DT Letter C1 NIDA, Bethesda, MD 20892 USA. RP Duffy, SQ (reprint author), NIDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JAN-FEB PY 2010 VL 29 IS 1 BP 222 EP 222 PG 1 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 539JZ UT WOS:000273251500045 PM 20063457 ER PT J AU Nelson, DE AF Nelson, David E. TI Commentary on oMapping Health Communication Scholarship: Breadth, Depth, and Agenda of Published Research in Health Communicationo: Implications for Reaching Practitioners With Communication Research SO HEALTH COMMUNICATION LA English DT Editorial Material C1 NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Nelson, DE (reprint author), NCI, Canc Prevent Fellowship Program, 6120 Execut Blvd,Suite 150E, Bethesda, MD 20892 USA. EM nelsonde@mail.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1041-0236 J9 HEALTH COMMUN JI Health Commun. PY 2010 VL 25 IS 6-7 BP 542 EP 543 AR PII 926890881 DI 10.1080/10410236.2010.497916 PG 2 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 650MD UT WOS:000281852700013 PM 20845137 ER PT J AU Holmberg, C Parascandola, M AF Holmberg, Christine Parascandola, Mark TI Individualised risk estimation and the nature of prevention SO HEALTH RISK & SOCIETY LA English DT Article DE risk; risk analysis; risk communication; uncertainty; risk management; breast cancer ID BREAST-CANCER RISK; UNITED-STATES; PREDICTION MODEL; HEART-DISEASE; ABSOLUTE RISK; GAIL MODEL; WOMEN; VALIDATION; FRAMINGHAM; PROBABILITIES AB Statistical risk models hold substantial promise for the practice of cancer prevention by helping to identify high risk populations and subsequently guide decisions about surveillance, further testing and treatments. They have come under criticism for creating new categories of disease-free but 'at risk' individuals. We analysed the debate over the interpretation of risk estimates to assess the importance of these models for the practice of cancer prevention. In particular, we focused on the Gail model for breast cancer risk assessment as a case study, because it is widely used and has been promoted directly to consumers. We describe the critiques that have been offered of the Gail model for individualised risk assessment, such as that classification of a new 'high risk' category may increase the use of medical intervention in otherwise healthy individuals. We then analyse the primary methodological limitations of individualised risk models, which are often overlooked in the application of these models and interpretation of their results. In particular, the application of statistical risk models like the Gail model to individuals fails to acknowledge the uncertainty surrounding estimates of individual risk. Moreover, putting the focus of risk management at the individual level minimises the influence of important environmental factors on risk, such as social influences and policies that may impact behaviour or outcomes. Overall, the increasing use of individualised risk estimates for individual decision-making may obscure the fact that successful disease prevention requires intervention on all levels, including the political, social, economic and individual level. C1 [Holmberg, Christine] Charite, Berlin Sch Publ Hlth, D-13353 Berlin, Germany. [Parascandola, Mark] NCI, Bethesda, MD 20892 USA. RP Holmberg, C (reprint author), Charite, Berlin Sch Publ Hlth, D-13353 Berlin, Germany. EM christine.holmberg@charite.de NR 49 TC 5 Z9 5 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1369-8575 J9 HEALTH RISK SOC JI Health Risk Soc. PY 2010 VL 12 IS 5 BP 441 EP 452 AR PII 927594836 DI 10.1080/13698575.2010.508835 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 659PF UT WOS:000282578700003 ER PT J AU Turkbey, EB Jorgensen, NW Johnson, WC Bertoni, AG Polak, JF Roux, AVD Tracy, RP Lima, JAC Bluemke, DA AF Turkbey, E. B. Jorgensen, N. W. Johnson, W. C. Bertoni, A. G. Polak, J. F. Roux, A. V. Diez Tracy, R. P. Lima, J. A. C. Bluemke, D. A. TI Physical activity and physiological cardiac remodelling in a community setting: the Multi-Ethnic Study of Atherosclerosis (MESA) SO HEART LA English DT Article ID LEFT-VENTRICULAR MASS; ATHLETES HEART; ENDURANCE; ECHOCARDIOGRAPHY; EXERCISE; SPORTS; ASSOCIATION; MORPHOLOGY; FEATURES; WOMEN AB Objective: To evaluate the association of physical activity with left ventricular structure and function in the general population in a community setting. Design: Cross-sectional study. Setting: The Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of subclinical atherosclerosis. Participants: A multiethnic sample of 4992 participants (aged 45-84 years; 52% female) free of clinically apparent cardiovascular disease. Interventions: Physical activity induces beneficial physiological cardiac remodelling in a cross-sectional study of non-athlete individuals. Main Outcome Measures: Left ventricular mass, volumes and function were assessed by cardiac magnetic resonance imaging. Physical activity, defined as intentional exercise and total moderate and vigorous physical activity, was assessed by a standard semiquantitative questionnaire. Results: Left ventricular mass and end-diastolic volume were positively associated with physical activity (eg, 1.4 g/m(2) (women) and 3.1 g/m(2) (men) greater left ventricular mass in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p = 0.05 and p < 0.001, respectively). Relationships were non-linear, with stronger positive associations at lower levels of physical activity (test for non-linearity; p = 0.02 and p = 0.03, respectively). Cardiac output and ejection fraction were unchanged with increased physical activity levels. Resting heart rate was lower in women and men with higher physical activity levels (eg, -2.6 beats/minute lower resting heart rate in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p < 0.001). Conclusions: In a community-based population free of clinically apparent cardiovascular disease, higher physical activity levels were associated with proportionally greater left ventricular mass and end-diastolic volume and lower resting heart rate. C1 [Bluemke, D. A.] NIH, Radiol & Imaging Sci RAD&IS, Ctr Clin, Bethesda, MD 20892 USA. [Jorgensen, N. W.; Johnson, W. C.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Bertoni, A. G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. [Polak, J. F.] Tufts Med Ctr, Dept Radiol, Boston, MA USA. [Roux, A. V. Diez] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Tracy, R. P.] Univ Vermont, Dept Pathol, Colchester, VT USA. [Tracy, R. P.] Univ Vermont, Dept Biochem, Colchester, VT USA. [Lima, J. A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. RP Bluemke, DA (reprint author), NIH, Radiol & Imaging Sci RAD&IS, Ctr Clin, 9000 Rockville Pike,Bldg 10,Rm 1C355, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169] FX This research was supported by contracts N01-HC-95159 to N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 30 TC 31 Z9 31 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD JAN PY 2010 VL 96 IS 1 BP 42 EP 48 DI 10.1136/hrt.2009.178426 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 534CH UT WOS:000272872600011 PM 19858139 ER PT J AU Maltsev, VA Lakatta, EG AF Maltsev, Victor A. Lakatta, Edward G. TI Yin and yang of the cardiac pacemaker clock system in health and disease SO HEART RHYTHM LA English DT Editorial Material ID SINOATRIAL NODE; RYANODINE RECEPTOR; CALCIUM-RELEASE; CELLS; OSCILLATIONS; AUTOMATICITY; MECHANISMS C1 [Maltsev, Victor A.; Lakatta, Edward G.] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000863-02] NR 20 TC 2 Z9 2 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JAN PY 2010 VL 7 IS 1 BP 96 EP 98 DI 10.1016/j.hrthm.2009.11.001 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 576ZI UT WOS:000276188500016 PM 20129289 ER PT S AU Boudvillain, M Walmacq, C Schwartz, A Jacquinot, F AF Boudvillain, Marc Walmacq, Celine Schwartz, Annie Jacquinot, Frederique BE Abdelhaleem, MM TI Simple Enzymatic Assays for the In Vitro Motor Activity of Transcription Termination Factor Rho from Escherichia coli SO HELICASES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Rho; transcription; termination; ring shaped; helicase; hexamer; molecular motor ID RNA; HELICASE; RECOGNITION; ACTIVATION AB The transcription termination factor Rho from Escherichia coli is a ring-shaped homo-hexameric protein that preferentially interacts with naked cytosine-rich Rut (Rho utilization) regions of nascent RNA transcripts. Once bound to the RNA chain, Rho uses ATP as ail energy source to produce mechanical work and disruptive forces that ultimately lead to the dissociation of the ternary transcription complex. Although transcription termination assays have been useful to study Rho activity in various experimental contexts, they do not report directly on Rho mechanisms and kinetics. Here, we describe complementary ATP-dependent RNA-DNA helicase and streptavidin displacement assays that can be used to monitor in vitro Rho's motor activity in a more direct and quantitative manner. C1 [Boudvillain, Marc; Schwartz, Annie; Jacquinot, Frederique] CNRS, Ctr Biophys Mol, UPR4301, Orleans 2, France. [Walmacq, Celine] NCI, NIH, Frederick, MD 21701 USA. RP Boudvillain, M (reprint author), CNRS, Ctr Biophys Mol, UPR4301, Orleans 2, France. OI Boudvillain, Marc/0000-0002-6398-9122 NR 20 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 SN 1064-3745 BN 978-1-60327-354-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 587 BP 137 EP 154 DI 10.1007/978-1-60327-355-8_10 D2 10.1007/978-1-60327-355-8 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNM27 UT WOS:000274938900010 PM 20225147 ER PT S AU Chen, CY Yedavalli, VRK Jeang, KT AF Chen, Chia-Yen Yedavalli, Venkat R. K. Jeang, Kuan-Teh BE Abdelhaleem, MM TI A Method to Study the Role of DDX3 RNA Helicase in HIV-1 SO HELICASES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE RNA helicases; human immunodeficiency virus type 1 (HIV-1); DEAD-Box domain; DDX3 AB Viral replication requires the use of host cell proteins and enzymes. Many viruses utilize viral helicases at various stages of their life cycle; these viruses have evolved to encode directly helicase or helicase-like proteins. In contrast, the genomes of retroviruses arc devoid of viral helicases. Human immunodeficiency virus (HIV-1) has adopted the ability to use one or more cellular RNA helicases for its replication life cycle. In this chapter, we briefly summarize the approach for assaying the RNA unwinding activity of RNA helicases measuring the effect of helicase inhibitors on HIV-1 replication. C1 [Chen, Chia-Yen; Yedavalli, Venkat R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Lab Mol, NIH, Bethesda, MD 20892 USA. RP Chen, CY (reprint author), NIAID, Mol Virol Sect, Lab Mol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 AI999999] NR 5 TC 1 Z9 1 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 978-1-60327-354-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 587 BP 281 EP 289 DI 10.1007/978-1-60327-355-8_20 D2 10.1007/978-1-60327-355-8 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNM27 UT WOS:000274938900020 PM 20225157 ER PT J AU Ballas, SK McCarthy, WF Guo, N Brugnara, C Kling, G Bauserman, RL Waclawiw, MA AF Ballas, Samir K. McCarthy, William F. Guo, Nan Brugnara, Carlo Kling, Gail Bauserman, Robert L. Waclawiw, Myron A. TI EARLY DETECTION OF RESPONSE TO HYDROXYUREA THERAPY IN PATIENTS WITH SICKLE CELL ANEMIA SO HEMOGLOBIN LA English DT Article DE Hydroxyurea (HU); Sickle cell anemia; Reticulocytes; Responders; Indices ID ERYTHROPOIETIC ACTIVITY; HEMOGLOBIN; MODEL AB Red blood cells (RBC) and reticulocyte parameters were determined on peripheral blood from a subset of patients enrolled in the multicenter study of hydroxyuea (HU) in sickle cell anemia. Multiple blood samples were obtained every 2 weeks. Cellular indices were measured by flow cytometry. Generalized linear models were used to determine the relationship between the longitudinal trajectories of RBC and reticulocyte indices and HU usage. There was a significant relationship between HU usage and most of the RBC and reticulocyte indices. Hydroxyurea produced higher value trajectories than those generated by placebo usage for the hemoglobin (Hb) content of both the RBCs and reticulocytes and for the mean corpuscular volume (MCV) of reticulocytes. These changes were first detected 10 weeks after starting HU and before the increase in Hb F levels. The data suggest that subtle and early markers of response to HU reside in the hemogram. C1 [Ballas, Samir K.] Thomas Jefferson Univ, FACP Cardeza Fdn, Dept Med, Jefferson Med Coll, Philadelphia, PA 19107 USA. [McCarthy, William F.; Guo, Nan; Bauserman, Robert L.] Maryland Med Res Inst, Baltimore, MD USA. [Brugnara, Carlo] Childrens Hosp, Boston, MA 02115 USA. [Kling, Gail] Siemens Healthcare Diagnost Inc, Tarrytown, NY USA. [Waclawiw, Myron A.] NHLBI, Bethesda, MD 20892 USA. RP Ballas, SK (reprint author), Thomas Jefferson Univ, FACP Cardeza Fdn, Dept Med, Jefferson Med Coll, 1015 Walnut St, Philadelphia, PA 19107 USA. EM samir.ballas@jefferson.edu FU National Heart, Lung and Blood Institute [NO1-HB-67129, UO1-HL45696]; Commonwealth of Pennsylvania for the Philadelphia region FX This study was supported in part by The National Heart, Lung and Blood Institute (NO1-HB-67129 and UO1-HL45696) and in part by the Sickle Cell Program of the Commonwealth of Pennsylvania for the Philadelphia region. NR 16 TC 4 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0363-0269 J9 HEMOGLOBIN JI Hemoglobin PY 2010 VL 34 IS 5 BP 424 EP 429 DI 10.3109/03630269.2010.513638 PG 6 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA 663ML UT WOS:000282891900002 PM 20854115 ER PT J AU Beasley, RP Alter, HJ Brandeau, ML Church, DR Evans, AA Hagan, H Hullett, S Maroushek, SR Mayer, RR McMahon, BJ Sepulveda, MJ So, S Thomas, DL Wright, LN Mitchell, AE Colvin, HM McGraw, KM Grossblatt, N Martinez, RM AF Beasley, R. Palmer Alter, Harvey J. Brandeau, Margaret L. Church, Daniel R. Evans, Alison A. Hagan, Holly Hullett, Sandral Maroushek, Stacene R. Mayer, Randall R. McMahon, Brian J. Sepulveda, Martin Jose So, Samuel Thomas, David L. Wright, Lester N. Mitchell, Abigail E. Colvin, Heather M. McGraw, Kathleen M. Grossblatt, Norman Martinez, Rose Marie CA Comm Prevention Control Viral Hepa Board Population Hlth Public Hlth BE Colvin, HM Mitchell, AE TI HEPATITIS AND LIVER CANCER A National Strategy for Prevention and Control of Hepatitis B and C Summary SO HEPATITIS AND LIVER CANCER: A NATIONAL STRATEGY FOR PREVENTION AND CONTROL OF HEPATITIS B AND C LA English DT Editorial Material; Book Chapter C1 [Beasley, R. Palmer] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. [Alter, Harvey J.] NIH, Infect Dis Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Brandeau, Margaret L.] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA. [Church, Daniel R.] Massachusetts Dept Hlth, Bur Infect Dis Prevent Response & Serv, Jamaica Plain, MA USA. [Evans, Alison A.] Drexel Univ, Sch Publ Hlth, Drexel Inst Biotechnol & Viral Res, Dept Epidemiol & Biostat, Doylestown, PA USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Drug Use & HIV Res, New York, NY USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Interdisciplinary Res Methods Core, New York, NY USA. [Hullett, Sandral] Cooper Green Hosp, Birmingham, AL USA. [Maroushek, Stacene R.] Hennepin Cty Med Ctr, Dept Pediat, Minneapolis, MN 55415 USA. [Mayer, Randall R.] Iowa Dept Publ Hlth, Bur HIV STD & Hepatitis, Des Moines, IA 50319 USA. [McMahon, Brian J.] Alaska Native Tribal Hlth Consortium, Liver Dis & Hepatitis Program, Anchorage, AK USA. [Sepulveda, Martin Jose] IBM Corp, Integrated Hlth Serv, Somers, NY USA. [So, Samuel] Stanford Univ, Sch Med, Asian Liver Ctr, Stanford, CA 94305 USA. [Thomas, David L.] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD USA. [Wright, Lester N.] New York Dept Correct Serv, Albany, NY USA. RP Beasley, RP (reprint author), Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-14628-9 PY 2010 BP 1 EP 17 PG 17 WC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health SC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health GA BC3XF UT WOS:000352025500001 ER PT J AU Beasley, RP Alter, HJ Brandeau, ML Church, DR Evans, AA Hagan, H Hullett, S Maroushek, SR Mayer, RR McMahon, BJ Sepulveda, MJ So, S Thomas, DL Wright, LN Mitchell, AE Colvin, HM McGraw, KM Grossblatt, N Martinez, RM AF Beasley, R. Palmer Alter, Harvey J. Brandeau, Margaret L. Church, Daniel R. Evans, Alison A. Hagan, Holly Hullett, Sandral Maroushek, Stacene R. Mayer, Randall R. McMahon, Brian J. Sepulveda, Martin Jose So, Samuel Thomas, David L. Wright, Lester N. Mitchell, Abigail E. Colvin, Heather M. McGraw, Kathleen M. Grossblatt, Norman Martinez, Rose Marie CA Comm Prevention Control Viral Hepa Board Population Hlth Public Hlth BE Colvin, HM Mitchell, AE TI HEPATITIS AND LIVER CANCER A National Strategy for Prevention and Control of Hepatitis B and C Introduction SO HEPATITIS AND LIVER CANCER: A NATIONAL STRATEGY FOR PREVENTION AND CONTROL OF HEPATITIS B AND C LA English DT Editorial Material; Book Chapter ID INJECTION-DRUG USERS; ACUTE VIRAL-HEPATITIS; HEALTH-CARE SETTINGS; VIRUS-INFECTION; UNITED-STATES; NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; PEGINTERFERON ALPHA-2A; GENETIC-VARIATION; GLOBAL BURDEN C1 [Beasley, R. Palmer] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. [Alter, Harvey J.] NIH, Infect Dis Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Brandeau, Margaret L.] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA. [Church, Daniel R.] Massachusetts Dept Hlth, Bur Infect Dis Prevent Response & Serv, Jamaica Plain, MA USA. [Evans, Alison A.] Drexel Univ, Sch Publ Hlth, Drexel Inst Biotechnol & Viral Res, Dept Epidemiol & Biostat, Doylestown, PA USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Drug Use & HIV Res, New York, NY USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Interdisciplinary Res Methods Core, New York, NY USA. [Hullett, Sandral] Cooper Green Hosp, Birmingham, AL USA. [Maroushek, Stacene R.] Hennepin Cty Med Ctr, Dept Pediat, Minneapolis, MN 55415 USA. [Mayer, Randall R.] Iowa Dept Publ Hlth, Bur HIV STD & Hepatitis, Des Moines, IA 50319 USA. [McMahon, Brian J.] Alaska Native Tribal Hlth Consortium, Liver Dis & Hepatitis Program, Anchorage, AK USA. [Sepulveda, Martin Jose] IBM Corp, Integrated Hlth Serv, Somers, NY USA. [So, Samuel] Stanford Univ, Sch Med, Asian Liver Ctr, Stanford, CA 94305 USA. [Thomas, David L.] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD USA. [Wright, Lester N.] New York Dept Correct Serv, Albany, NY USA. RP Beasley, RP (reprint author), Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. NR 95 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-14628-9 PY 2010 BP 19 EP 40 PG 22 WC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health SC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health GA BC3XF UT WOS:000352025500002 ER PT J AU Beasley, RP Alter, HJ Brandeau, ML Church, DR Evans, AA Hagan, H Hullett, S Maroushek, SR Mayer, RR McMahon, BJ Sepulveda, MJ So, S Thomas, DL Wright, LN Mitchell, AE Colvin, HM McGraw, KM Grossblatt, N Martinez, RM AF Beasley, R. Palmer Alter, Harvey J. Brandeau, Margaret L. Church, Daniel R. Evans, Alison A. Hagan, Holly Hullett, Sandral Maroushek, Stacene R. Mayer, Randall R. McMahon, Brian J. Sepulveda, Martin Jose So, Samuel Thomas, David L. Wright, Lester N. Mitchell, Abigail E. Colvin, Heather M. McGraw, Kathleen M. Grossblatt, Norman Martinez, Rose Marie CA Comm Prevention Control Viral Hepa Board Population Hlth Public Hlth BE Colvin, HM Mitchell, AE TI Surveillance SO HEPATITIS AND LIVER CANCER: A NATIONAL STRATEGY FOR PREVENTION AND CONTROL OF HEPATITIS B AND C LA English DT Article; Book Chapter ID HEPATITIS-C VIRUS; INJECTION-DRUG USERS; HUMAN-IMMUNODEFICIENCY-VIRUS; PUBLIC-HEALTH SURVEILLANCE; ACUTE VIRAL-HEPATITIS; UNITED-STATES; B-VIRUS; INFECTIOUS-DISEASES; MEDICAL-RECORDS; FOLLOW-UP C1 [Beasley, R. Palmer] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. [Alter, Harvey J.] NIH, Infect Dis Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Brandeau, Margaret L.] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA. [Church, Daniel R.] Massachusetts Dept Hlth, Bur Infect Dis Prevent Response & Serv, Jamaica Plain, MA USA. [Evans, Alison A.] Drexel Univ, Sch Publ Hlth, Drexel Inst Biotechnol & Viral Res, Dept Epidemiol & Biostat, Doylestown, PA USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Drug Use & HIV Res, New York, NY USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Interdisciplinary Res Methods Core, New York, NY USA. [Hullett, Sandral] Cooper Green Hosp, Birmingham, AL USA. [Maroushek, Stacene R.] Hennepin Cty Med Ctr, Dept Pediat, Minneapolis, MN 55415 USA. [Mayer, Randall R.] Iowa Dept Publ Hlth, Bur HIV STD & Hepatitis, Des Moines, IA 50319 USA. [McMahon, Brian J.] Alaska Native Tribal Hlth Consortium, Liver Dis & Hepatitis Program, Anchorage, AK USA. [Sepulveda, Martin Jose] IBM Corp, Integrated Hlth Serv, Somers, NY USA. [So, Samuel] Stanford Univ, Sch Med, Asian Liver Ctr, Stanford, CA 94305 USA. [Thomas, David L.] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD USA. [Wright, Lester N.] New York Dept Correct Serv, Albany, NY USA. RP Beasley, RP (reprint author), Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. NR 94 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-14628-9 PY 2010 BP 41 EP 78 PG 38 WC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health SC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health GA BC3XF UT WOS:000352025500003 ER PT J AU Beasley, RP Alter, HJ Brandeau, ML Church, DR Evans, AA Hagan, H Hullett, S Maroushek, SR Mayer, RR McMahon, BJ Sepulveda, MJ So, S Thomas, DL Wright, LN Mitchell, AE Colvin, HM McGraw, KM Grossblatt, N Martinez, RM AF Beasley, R. Palmer Alter, Harvey J. Brandeau, Margaret L. Church, Daniel R. Evans, Alison A. Hagan, Holly Hullett, Sandral Maroushek, Stacene R. Mayer, Randall R. McMahon, Brian J. Sepulveda, Martin Jose So, Samuel Thomas, David L. Wright, Lester N. Mitchell, Abigail E. Colvin, Heather M. McGraw, Kathleen M. Grossblatt, Norman Martinez, Rose Marie CA Comm Prevention Control Viral Hepa Board Population Hlth Public Hlth BE Colvin, HM Mitchell, AE TI Knowledge and Awareness About Chronic Hepatitis B and Hepatitis C SO HEPATITIS AND LIVER CANCER: A NATIONAL STRATEGY FOR PREVENTION AND CONTROL OF HEPATITIS B AND C LA English DT Article; Book Chapter ID INJECTION-DRUG USERS; VIETNAMESE-AMERICAN MEN; PRIMARY-CARE PHYSICIANS; LIVER-CANCER; UNITED-STATES; VIRUS-INFECTION; SYRINGE EXCHANGE; ASIAN-AMERICANS; HEPATOCELLULAR-CARCINOMA; PREVENTION PROGRAM C1 [Beasley, R. Palmer] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. [Alter, Harvey J.] NIH, Infect Dis Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Brandeau, Margaret L.] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA. [Church, Daniel R.] Massachusetts Dept Hlth, Bur Infect Dis Prevent Response & Serv, Jamaica Plain, MA USA. [Evans, Alison A.] Drexel Univ, Sch Publ Hlth, Drexel Inst Biotechnol & Viral Res, Dept Epidemiol & Biostat, Doylestown, PA USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Drug Use & HIV Res, New York, NY USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Interdisciplinary Res Methods Core, New York, NY USA. [Hullett, Sandral] Cooper Green Hosp, Birmingham, AL USA. [Maroushek, Stacene R.] Hennepin Cty Med Ctr, Dept Pediat, Minneapolis, MN 55415 USA. [Mayer, Randall R.] Iowa Dept Publ Hlth, Bur HIV STD & Hepatitis, Des Moines, IA 50319 USA. [McMahon, Brian J.] Alaska Native Tribal Hlth Consortium, Liver Dis & Hepatitis Program, Anchorage, AK USA. [Sepulveda, Martin Jose] IBM Corp, Integrated Hlth Serv, Somers, NY USA. [So, Samuel] Stanford Univ, Sch Med, Asian Liver Ctr, Stanford, CA 94305 USA. [Thomas, David L.] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD USA. [Wright, Lester N.] New York Dept Correct Serv, Albany, NY USA. RP Beasley, RP (reprint author), Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. NR 118 TC 0 Z9 0 U1 2 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-14628-9 PY 2010 BP 79 EP 107 PG 29 WC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health SC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health GA BC3XF UT WOS:000352025500004 ER PT J AU Beasley, RP Alter, HJ Brandeau, ML Church, DR Evans, AA Hagan, H Hullett, S Maroushek, SR Mayer, RR McMahon, BJ Sepulveda, MJ So, S Thomas, DL Wright, LN Mitchell, AE Colvin, HM McGraw, KM Grossblatt, N Martinez, RM AF Beasley, R. Palmer Alter, Harvey J. Brandeau, Margaret L. Church, Daniel R. Evans, Alison A. Hagan, Holly Hullett, Sandral Maroushek, Stacene R. Mayer, Randall R. McMahon, Brian J. Sepulveda, Martin Jose So, Samuel Thomas, David L. Wright, Lester N. Mitchell, Abigail E. Colvin, Heather M. McGraw, Kathleen M. Grossblatt, Norman Martinez, Rose Marie CA Comm Prevention Control Viral Hepa Board Population Hlth Public Hlth BE Colvin, HM Mitchell, AE TI Immunization SO HEPATITIS AND LIVER CANCER: A NATIONAL STRATEGY FOR PREVENTION AND CONTROL OF HEPATITIS B AND C LA English DT Article; Book Chapter ID HEPATITIS-B VACCINATION; INJECTION-DRUG USERS; SEXUALLY-TRANSMITTED-DISEASES; UNITED-STATES; C VIRUS; COST-EFFECTIVENESS; VIRAL-HEPATITIS; INFORMATION-SYSTEMS; SYRINGE EXCHANGE; SAN-FRANCISCO C1 [Beasley, R. Palmer] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. [Alter, Harvey J.] NIH, Infect Dis Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Brandeau, Margaret L.] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA. [Church, Daniel R.] Massachusetts Dept Hlth, Bur Infect Dis Prevent Response & Serv, Jamaica Plain, MA USA. [Evans, Alison A.] Drexel Univ, Sch Publ Hlth, Drexel Inst Biotechnol & Viral Res, Dept Epidemiol & Biostat, Doylestown, PA USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Drug Use & HIV Res, New York, NY USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Interdisciplinary Res Methods Core, New York, NY USA. [Hullett, Sandral] Cooper Green Hosp, Birmingham, AL USA. [Maroushek, Stacene R.] Hennepin Cty Med Ctr, Dept Pediat, Minneapolis, MN 55415 USA. [Mayer, Randall R.] Iowa Dept Publ Hlth, Bur HIV STD & Hepatitis, Des Moines, IA 50319 USA. [McMahon, Brian J.] Alaska Native Tribal Hlth Consortium, Liver Dis & Hepatitis Program, Anchorage, AK USA. [Sepulveda, Martin Jose] IBM Corp, Integrated Hlth Serv, Somers, NY USA. [So, Samuel] Stanford Univ, Sch Med, Asian Liver Ctr, Stanford, CA 94305 USA. [Thomas, David L.] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD USA. [Wright, Lester N.] New York Dept Correct Serv, Albany, NY USA. RP Beasley, RP (reprint author), Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. NR 122 TC 0 Z9 0 U1 1 U2 1 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-14628-9 PY 2010 BP 109 EP 145 PG 37 WC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health SC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health GA BC3XF UT WOS:000352025500005 ER PT J AU Beasley, RP Alter, HJ Brandeau, ML Church, DR Evans, AA Hagan, H Hullett, S Maroushek, SR Mayer, RR McMahon, BJ Sepulveda, MJ So, S Thomas, DL Wright, LN Mitchell, AE Colvin, HM McGraw, KM Grossblatt, N Martinez, RM AF Beasley, R. Palmer Alter, Harvey J. Brandeau, Margaret L. Church, Daniel R. Evans, Alison A. Hagan, Holly Hullett, Sandral Maroushek, Stacene R. Mayer, Randall R. McMahon, Brian J. Sepulveda, Martin Jose So, Samuel Thomas, David L. Wright, Lester N. Mitchell, Abigail E. Colvin, Heather M. McGraw, Kathleen M. Grossblatt, Norman Martinez, Rose Marie CA Comm Prevention Control Viral Hepa Board Population Hlth Public Hlth BE Colvin, HM Mitchell, AE TI Viral Hepatitis Services SO HEPATITIS AND LIVER CANCER: A NATIONAL STRATEGY FOR PREVENTION AND CONTROL OF HEPATITIS B AND C LA English DT Article; Book Chapter ID INJECTION-DRUG-USERS; C-VIRUS-INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; PREVENT PERINATAL TRANSMISSION; COMMUNITY-BASED ORGANIZATIONS; NEEDLE EXCHANGE PROGRAMS; B SURFACE-ANTIGEN; SEXUALLY-TRANSMITTED-DISEASES; COST-EFFECTIVENESS ANALYSIS; SYRINGE VENDING MACHINES C1 [Beasley, R. Palmer] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. [Alter, Harvey J.] NIH, Infect Dis Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Brandeau, Margaret L.] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA. [Church, Daniel R.] Massachusetts Dept Hlth, Bur Infect Dis Prevent Response & Serv, Jamaica Plain, MA USA. [Evans, Alison A.] Drexel Univ, Sch Publ Hlth, Drexel Inst Biotechnol & Viral Res, Dept Epidemiol & Biostat, Doylestown, PA USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Drug Use & HIV Res, New York, NY USA. [Hagan, Holly] NYU, Coll Nursing, Ctr Interdisciplinary Res Methods Core, New York, NY USA. [Hullett, Sandral] Cooper Green Hosp, Birmingham, AL USA. [Maroushek, Stacene R.] Hennepin Cty Med Ctr, Dept Pediat, Minneapolis, MN 55415 USA. [Mayer, Randall R.] Iowa Dept Publ Hlth, Bur HIV STD & Hepatitis, Des Moines, IA 50319 USA. [McMahon, Brian J.] Alaska Native Tribal Hlth Consortium, Liver Dis & Hepatitis Program, Anchorage, AK USA. [Sepulveda, Martin Jose] IBM Corp, Integrated Hlth Serv, Somers, NY USA. [So, Samuel] Stanford Univ, Sch Med, Asian Liver Ctr, Stanford, CA 94305 USA. [Thomas, David L.] Johns Hopkins Sch Med, Dept Med, Div Infect Dis, Baltimore, MD USA. [Wright, Lester N.] New York Dept Correct Serv, Albany, NY USA. RP Beasley, RP (reprint author), Univ Texas Houston, Sch Publ Hlth, Houston, TX 77251 USA. NR 242 TC 0 Z9 0 U1 1 U2 1 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-14628-9 PY 2010 BP 147 EP 207 PG 61 WC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health SC Oncology; Gastroenterology & Hepatology; Public, Environmental & Occupational Health GA BC3XF UT WOS:000352025500006 ER PT B AU Budhu, A Ji, JF Wang, XW AF Budhu, Anuradha Ji, Junfang Wang, Xin Wei BE Carr, BI TI Genomic Profiling of Human Hepatocellular Carcinoma SO HEPATOCELLULAR CARCINOMA: DIAGNOSIS AND TREATMENT, SECOND EDITION SE Current Clinical Oncology Series LA English DT Article; Book Chapter DE Hepatocellular carcinoma; molecular marker; gene expression profiling; microarray; liver disease ID HEPATITIS-C VIRUS; GENE-EXPRESSION PROFILES; ENDOTHELIAL GROWTH-FACTOR; EARLY INTRAHEPATIC RECURRENCE; CDNA MICROARRAY ANALYSIS; TUMOR-SUPPRESSOR GENE; CHRONIC LIVER-DISEASE; HUMAN BREAST-CANCER; B-VIRUS; FACTOR-II AB Numerous studies of human gene function have been launched since the sequencing of the human genome. Global Molecular profiling studies of hepatocellular carcinoma (HCC) are providing a comprehensive view of the expression changes that occur during the carcinogenic process and are uncovering promising biomarkers with clinical potential. In this chapter, an overview of recent gene expression profiling of human HCC is provided along with a summation of the mechanistic, diagnostic, and prognostic significance of these findings. Emerging concepts associated with these studies are also addressed and biomarkers present in serum are highlighted. Current profiling studies, conducted on multiple array platforms, are powerful tools which have provided useful clues to begin to unravel the mechanisms of HCC biology and improve clinical outcome. C1 [Budhu, Anuradha; Ji, Junfang; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Budhu, A (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Canc Res Ctr,NIH, Bldg 37, Bethesda, MD 20892 USA. NR 231 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 978-1-60327-373-2 J9 CURR CLIN ONCOL PY 2010 BP 129 EP 180 DI 10.1007/978-1-60327-376-3_5 D2 10.1007/978-1-60327-376-3 PG 52 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BLX28 UT WOS:000271269800005 ER PT J AU Gao, B AF Gao, Bin TI Natural Killer Group 2 Member D, Its Ligands, and Liver Disease: Good or Bad? SO HEPATOLOGY LA English DT Editorial Material ID ACTIVATED STELLATE CELLS; PRIMARY SCLEROSING CHOLANGITIS; HEPATITIS-B-VIRUS; KUPFFER CELLS; NK CELLS; INJURY; NKG2D; FIBROSIS; TRAIL; SUSCEPTIBILITY C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Room 2S-33,5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov FU Intramural NIH HHS [Z99 AA999999, ZIA AA000368-08] NR 28 TC 13 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2010 VL 51 IS 1 BP 8 EP 11 DI 10.1002/hep.23320 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 541RV UT WOS:000273438400003 PM 20034045 ER PT J AU Promrat, K Kleiner, DE Niemeier, HM Jackvony, E Kearns, M Wands, JR Fava, JL Wing, RR AF Promrat, Kittichai Kleiner, David E. Niemeier, Heather M. Jackvony, Elizabeth Kearns, Marie Wands, Jack R. Fava, Joseph L. Wing, Rena R. TI Randomized Controlled Trial Testing the Effects of Weight Loss on Nonalcoholic Steatohepatitis SO HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; TERM DIETARY INTERVENTION; PLACEBO-CONTROLLED TRIAL; LIFE-STYLE MODIFICATION; CARDIOVASCULAR-DISEASE; OVERWEIGHT PATIENTS; METABOLIC SYNDROME; FOOD PROVISION; OBESE-PATIENTS; REDUCTION AB Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that is strongly associated with obesity. Currently, there is no approved therapy for NASH. Weight reduction is typically recommended, but efficacy data are lacking. We performed a randomized controlled trial to examine the effects of lifestyle intervention using a combination of diet, exercise, and behavior modification, with a goal of 7% to 10% weight reduction, on clinical parameters of NASH. The primary outcome measure was the change in NASH histological activity score (NAS) after 48 weeks of intervention. Thirty-one overweight or obese individuals (body mass index [BMI], 25-40 kg/m(2)) with biopsy-proven NASH were randomized in a 2:1 ratio to receive intensive lifestyle intervention (LS) or structured education (control). After 48 weeks of intervention, participants assigned to LS lost an average of 9.3% of their weight versus 0.2% in the control group (P = 0.003). A higher proportion of participants in the LS group had a reduction of NAS of at least 3 points or had posttreatment NAS of 2 or less as compared with the control group (72% versus 30%, P = 0.03). NAS improved significantly in the LS group (from 4.4 to 2.0) in comparison with the control group (from 4.9 to 3.5) (P = 0.05). Percent weight reduction correlated significantly with improvement in NAS (r = 0.497, P = 0.007). Participants who achieved the study weight loss goal (2:7%), compared with those who lost less than 7%, had significant improvements in steatosis (-1.36 versus -0.41, P < 0.001), lobular inflammation (-0.82 versus -0.24, P = 0.03), ballooning injury (-1.27 versus -0.53, P = 0.03) and NAS (-3.45 versus -1.18, P < 0.001). Conclusion: Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH. (HEPATOLOGY 2010;51:121-129.) C1 [Promrat, Kittichai; Wands, Jack R.] Brown Univ, Warren Alpert Med Sch, Div Gastroenterol & Hepatol, Providence, RI 02903 USA. [Niemeier, Heather M.; Jackvony, Elizabeth; Kearns, Marie; Fava, Joseph L.; Wing, Rena R.] Brown Univ, Warren Alpert Med Sch, Weight Control & Diabet Res Ctr, Providence, RI 02903 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Promrat, Kittichai] Providence Vet Affairs Med Ctr, Providence, RI USA. [Niemeier, Heather M.] Univ Wisconsin, Dept Psychol, Whitewater, WI 53190 USA. RP Promrat, K (reprint author), Brown Univ, Warren Alpert Med Sch, Div Gastroenterol & Hepatol, 110 Lockwood St,Suite 116, Providence, RI 02903 USA. EM Kittichai_Promrat@Brown.edu OI Kleiner, David/0000-0003-3442-4453 FU National Institutes of Health [5R03DK67263-2]; National Cancer Institute FX Supported by the National Institutes of Health, 5R03DK67263-2. Supported in part by the Intramural Research Program of the National Cancer Institute, NIH (D. E A). NR 42 TC 363 Z9 378 U1 2 U2 20 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2010 VL 51 IS 1 BP 121 EP 129 DI 10.1002/hep.23276 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 541RV UT WOS:000273438400017 PM 19827166 ER PT J AU Modi, AA Feld, JJ Park, Y Kleiner, DE Everhart, JE Liang, TJ Hoofnagle, JH AF Modi, Apurva A. Feld, Jordan J. Park, Yoon Kleiner, David E. Everhart, James E. Liang, T. Jake Hoofnagle, Jay H. TI Increased Caffeine Consumption Is Associated with Reduced Hepatic Fibrosis SO HEPATOLOGY LA English DT Article ID GAMMA-GLUTAMYL-TRANSFERASE; SELF-DEFENSE OFFICIALS; COFFEE CONSUMPTION; HEPATOCELLULAR-CARCINOMA; TEA CONSUMPTION; UNITED-STATES; LIVER-CANCER; GREEN TEA; RISK; JAPAN AB Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. This study was undertaken to use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Patients undergoing liver biopsy completed a detailed caffeine questionnaire on three occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. One hundred seventy-seven patients (99 male, 104 white, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75(th) percentile for the cohort (308 mg = approximately 2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.80; P = 0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index, and alcohol intake in all patients (OR, 0.25; 95% CI, 0.09-0.67; P = 0.006), as well as the subset with HCV infection (OR, 0.19; 95% CI, 0.05-0.66; P = 0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis. (HEPATOLOGY 2010;51:201-209.) C1 [Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Feld, Jordan J.] Univ Toronto, Toronto Western Hosp, Liver Clin, Div Gastroenterol, Toronto, ON M5T 2S8, Canada. [Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bldg 31,Rm 9A27, Bethesda, MD 20892 USA. EM HoofnagleJ@extra.niddk.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS [NIH0012311498]; PHS HHS [NIH0012311498] NR 30 TC 94 Z9 99 U1 2 U2 17 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2010 VL 51 IS 1 BP 201 EP 209 DI 10.1002/hep.23279 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 541RV UT WOS:000273438400025 PM 20034049 ER PT J AU Fannin, RD Russo, M O'Connell, TM Gerrish, K Winnike, JH Macdonald, J Newton, J Malik, S Sieber, SO Parker, J Shah, R Zhou, T Watkins, PB Paules, RS AF Fannin, Rick D. Russo, Mark O'Connell, Thomas M. Gerrish, Kevin Winnike, Jason H. Macdonald, Jeffrey Newton, Jack Malik, Shahid Sieber, Stella O. Parker, Joel Shah, Ruchir Zhou, Tong Watkins, Paul B. Paules, Richard S. TI Acetaminophen Dosing of Humans Results in Blood Transcriptome and Metabolome Changes Consistent with Impaired Oxidative Phosphorylation SO HEPATOLOGY LA English DT Article ID GENE-EXPRESSION; LACTIC-ACIDOSIS; LYMPHOCYTES; CELLS; HEPATOTOXICITY; DEFICIENCY; PHENOTYPE; SURVIVAL; INJURY AB The diagnosis and management of drug-induced liver injury (DILI) is hindered by the limited utility of traditional clinical chemistries. It has recently been shown that hepatotoxicants can produce compound-specific changes in the peripheral blood (PB) transcriptome in rodents, suggesting that the blood transcriptome might provide new biomarkers of DILI. To investigate in humans, we used DNA microarrays as well as serum metabolomic methods to characterize changes in the transcriptome and metabolome in serial PB samples obtained from six healthy adults treated with a 4-g bolus dose of acetaminophen (APAP) and from three receiving placebo. Treatment did not cause liver injury as assessed by traditional liver chemistries. However, 48 hours after exposure, treated subjects showed marked down-regulation of genes involved in oxidative phosphorylation/mitochondrial function that was not observed in the placebos (P < 1.66E-19). The magnitude of down-regulation was positively correlated with the percent of APAP converted to the reactive metabolite N-acetyl-p-benzoquinone-imide (NAPQI) (r = 0.739; P = 0.058). In addition, unbiased analysis of the serum metabolome revealed an increase in serum lactate from 24 to 72 hours postdosing in the treated subjects alone (P < 0.005). Similar PB transcriptome changes were observed in human overdose patients and rats receiving toxic doses. Conclusion: The single 4-g APAP dose produced a transcriptome signature in PB cells characterized by down-regulation of oxidative phosphorylation genes accompanied by increased serum lactate. Similar gene expression changes were observed in rats and several patients after consuming hepatotoxic doses of APAP. The timing of the changes and the correlation with NAPQI production are consistent with mechanisms known to underlie APAP hepatoxicity. These studies support the further exploration of the blood transcriptome for biomarkers of DILI. (HEPATOLOGY 2010;51:227-236.) C1 [Fannin, Rick D.; Gerrish, Kevin; Sieber, Stella O.; Paules, Richard S.] NIEHS, Microarray Grp, NIH, Res Triangle Pk, NC 27709 USA. [Russo, Mark] Carolinas Med Ctr, Liver Transplant Unit, Charlotte, NC 28203 USA. [O'Connell, Thomas M.; Zhou, Tong; Watkins, Paul B.] Hamner Inst, Res Triangle Pk, NC USA. [O'Connell, Thomas M.; Zhou, Tong; Watkins, Paul B.] Univ N Carolina, Ctr Drug Safety Sci, Res Triangle Pk, NC USA. [O'Connell, Thomas M.] Univ N Carolina, Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. [Winnike, Jason H.; Macdonald, Jeffrey] Univ N Carolina, Sch Med, Dept Biomed Engn, Chapel Hill, NC USA. [Newton, Jack; Malik, Shahid] Chenomx, Edmonton, AB, Canada. [Parker, Joel] Express Anal, Durham, NC USA. [Shah, Ruchir] SRA Int, Durham, NC USA. RP Paules, RS (reprint author), NIEHS, Microarray Grp, NIH, POB 12233,Mail Drop D2-03, Res Triangle Pk, NC 27709 USA. EM paules@niehs.nih.gov FU National Institute of Environmental Health Sciences [P30ES10126]; NIH [R37 GM38149, K23 RR21857-01]; University of North Carolina General Clinical Research Center [M000046] FX Supported, in part, by the Intramural Research Program of the National Institute of Environmental Health Sciences, NIH, and National Institute of Environmental Health Sciences grant P30ES10126, NIH grants R37 GM38149 and K23 RR21857-01, and the University of North Carolina General Clinical Research Center grant M000046. NR 25 TC 48 Z9 52 U1 5 U2 16 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2010 VL 51 IS 1 BP 227 EP 236 DI 10.1002/hep.23330 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 541RV UT WOS:000273438400028 PM 19918972 ER PT S AU Phillips, RS Miles, EW McPhie, P Marchal, S Lange, R Holtermann, G Goody, RS AF Phillips, Robert S. Miles, Edith W. McPhie, Peter Marchal, Stephane Lange, Reinhard Holtermann, Georg Goody, Roger S. BE Bartlett, DH TI Effects of hydrostatic pressure on the conformational equilibrium of tryptophan synthase from Salmonella typhimurium SO HIGH-PRESSURE BIOSCIENCE AND BIOTECHNOLOGY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 5th International High-Pressure Bioscience and Biotechnology Conference CY SEP 15-19, 2008 CL La Jolla, CA DE tryptophan synthase; allostery; pyridoxal-5 '-phosphate; compressibility; solution ID BIENZYME COMPLEX; ALPHA(2)BETA(2) COMPLEX; MONOVALENT CATIONS; SUBSTRATE-SPECIFICITY; ALLOSTERIC REGULATION; L-SERINE; ACTIVE-SITES; ALPHA; BETA; LIGANDS AB A wide range of parameters influence allosteric communications between the alpha- and beta-subunits of the Trp synthase alpha(2)beta(2) multienzyme complex with L-Ser, including monovalent cations, pH, temperature, ligands, organic solvents, and hydrostatic pressure. The conformational change from closed to open can be monitored either by absorbance at 423 nm or fluorescence at 495 nm from the pyridoxal-5 '-phosphate-L-Ser complex. Pressure perturbation was used to quantify the effects of monovalent cations, ligands, and mutations on the conformational equilibrium of Trp synthase. P-jump kinetics in the presence of Na(+), NH(4)(+), and Na(+) together with benzimidazole were also examined. The plots of Ink versus P are nonlinear and require a compressibility (beta(double dagger)(omicron)) term to obtain a good fit. beta(double dagger)(omicron) is positive for the Na(+) enzyme but negative for NH(4)(+) and Na(+) with benzimidazole. These results suggest that there is a large contribution of solvation to the kinetics of the conformational change of Trp synthase. The relaxation kinetics are also different if the P-jumps are made by increasing or decreasing pressure, suggesting that the enzyme conformations are ensembles of microstates. C1 [Phillips, Robert S.] Univ Georgia, Dept Chem, Athens, GA 30602 USA. [Phillips, Robert S.] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. [Miles, Edith W.; McPhie, Peter] NIDDK, NIH, Bethesda, MD USA. [Marchal, Stephane; Lange, Reinhard] Univ Montpellier 2, UMR S710, Montpellier, France. [Marchal, Stephane; Lange, Reinhard] INSERM, U710, Montpellier, France. [Holtermann, Georg; Goody, Roger S.] Max Planck Inst Mol Physiol, D-44139 Dortmund, Germany. RP Phillips, RS (reprint author), Univ Georgia, Dept Chem, Athens, GA 30602 USA. EM rsphillips@chem.uga.edu RI Goody, Roger/J-8845-2014; OI Goody, Roger/0000-0002-0772-0444; Phillips, Robert/0000-0001-8710-562X FU Intramural NIH HHS [ZIA DK024964-05] NR 30 TC 1 Z9 1 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-771-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1189 BP 95 EP 103 DI 10.1111/j.1749-6632.2009.05201.x PG 9 WC Biotechnology & Applied Microbiology; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA BOU68 UT WOS:000277662500013 PM 20233374 ER PT B AU Cobb, S Lawrence, JJ AF Cobb, Stuart Lawrence, J. Josh BE Cutsuridis, V Graham, B Cobb, S Vida, I TI Neuromodulation of Hippocampal Cells and Circuits SO HIPPOCAMPAL MICROCIRCUITS: A COMPUTATIONAL MODELER'S RESOURCE BOOK SE Springer Series in Computational Neuroscience LA English DT Article; Book Chapter ID LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; RAT DENTATE GYRUS; EXCITATORY SYNAPTIC-TRANSMISSION; CA1 PYRAMIDAL NEURONS; NICOTINIC ACETYLCHOLINE-RECEPTORS; THYROTROPIN-RELEASING-HORMONE; IN-SITU HYBRIDIZATION; STRATUM-ORIENS INTERNEURONS; FAST-SPIKING INTERNEURONS C1 [Cobb, Stuart; Lawrence, J. Josh] Univ Glasgow, Fac Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland. [Lawrence, J. Josh] Univ Montana, Dept Biomed & Pharmaceut Sci, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. RP Lawrence, JJ (reprint author), Univ Glasgow, Fac Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland. EM s.cobb@bio.gla.ac.uk; lawrenjo@mail.nih.gov NR 435 TC 5 Z9 5 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0995-4 J9 SPR SER COMPUT NEURO JI Springer Ser. Comput. Neurosci. PY 2010 VL 5 BP 187 EP 246 DI 10.1007/978-1-4419-0996-1_7 D2 10.1007/978-1-4419-0996-1 PG 60 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA BOC31 UT WOS:000276164100008 ER PT J AU Steinvorth, S Wang, CM Ulbert, I Schomer, D Halgren, E AF Steinvorth, Sarah Wang, Chunmao Ulbert, Istvan Schomer, Donald Halgren, Eric TI Human Entorhinal Gamma and Theta Oscillations Selective for Remote Autobiographical Memory SO HIPPOCAMPUS LA English DT Article DE remote memory; medial temporal lobes; episodic memory; consolidation; intracranial EEG ID WORKING-MEMORY; DECLARATIVE MEMORY; FUNCTIONAL NEUROANATOMY; PHASE SYNCHRONIZATION; SEMANTIC MEMORY; BAND ACTIVITY; HIPPOCAMPAL; RETRIEVAL; TASK; EEG AB Current source densities in different layers of the human entorhinal cortex (ER) were recorded using a linear array of 24 micro-electrodes during three memory conditions: a remote autobiographical condition eliciting recollections of events that occurred 10 or more years ago in the participant's past, a semantic icon condition invoking the mental image of a well-known object, and a semantic knowledge condition asking about general information. Our data demonstrate theta, gamma, and delta oscillations in left ER particularly for remote autobiographical memory. Gamma is predominant in hippocampally projecting layers during presentation of the memory cue, whereas the a is prolonged and dominant in cortically projecting layers during memory retrieval. Gamma interactions between ER and hippocampal formation (HF) may elicit an HF contribution to recall under influences relayed from the association cortex (AC). This contribution may then be relayed back to AC during retrieval of the memory orchestrated by theta interactions with ER. Accordingly, theta oscillations were recorded simultaneously in frontal and temporal cortices. (C) 2009 Wiley-Liss, Inc. C1 [Steinvorth, Sarah] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, MIT,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Wang, Chunmao] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. [Ulbert, Istvan] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. [Ulbert, Istvan] Peter Pazmany Catholic Univ, Dept Informat Technol, Budapest, Hungary. [Schomer, Donald] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Halgren, Eric] Univ Calif San Diego, Ctr Multimodal Imaging, San Diego, CA 92103 USA. RP Steinvorth, S (reprint author), Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, MIT,Massachusetts Gen Hosp, Bld 149 13th St, Charlestown, MA 02129 USA. EM ssteinv@nmr.mgh.harvard.edu RI Ulbert, Istvan/F-2213-2010 FU NIH [NS18741, NS44623] FX Grant sponsor: NIH; Grant numbers: NS18741, NS44623 NR 62 TC 19 Z9 22 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2010 VL 20 IS 1 BP 166 EP 173 DI 10.1002/hipo.20597 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 545JF UT WOS:000273727600018 PM 19338019 ER PT J AU Neddens, J Buonanno, A AF Neddens, Joerg Buonanno, Andres TI Selective Populations of Hippocampal Interneurons Express ErbB4 and Their Number and Distribution Is Altered in ErbB4 Knockout Mice SO HIPPOCAMPUS LA English DT Article DE calcium binding protein; GABA; inhibition; neuregulin; schizophrenia ID CENTRAL-NERVOUS-SYSTEM; PERIKARYAL PARVALBUMIN IMMUNOREACTIVITY; NEUREGULIN RECEPTOR ERBB4; LONG-TERM POTENTIATION; NITRIC-OXIDE SYNTHASE; GABAERGIC NEURONS; MOUSE HIPPOCAMPUS; QUANTITATIVE-ANALYSIS; NETWORK OSCILLATIONS; RAT HIPPOCAMPUS AB Neuregulins (NRGs) are ligands of ErbB receptor tyrosine kinases. The NRG1-ErbB4 pathway has been shown to modulate hippocampal synaptic plasticity and network oscillations in the adult rodent brain. To identify cells that mediate these effects, here we determine the expression pattern of ErbB4 in four functionally distinct classes of interneurons that represent the majority of all inhibitory neurons in the adult hippocampus. On the basis of data from nine mice and 25,000 cells, we show that ErbB4 is expressed in cells that are positive for cholecystokinin (CCK, 54%), parvalbumin (PV, 42%), or neuronal nitric oxide synthase (nNOS, 39%) in a layer-specific and region-specific manner, whereas cells expressing somatostatin (SOM) are rarely immunoreactive for ErbB4 (1%). We next compared the numerical density (cells/mm(3)) and the distribution of interneurons between ErbB4-/- mice and wildtype controls. Based on data from 25 mice and 56,000 cells, we detected reductions of PV-positive and nNOS-positive cells in knockouts (-24% and -27%, respectively) but only a minor reduction of CCK-positive cells; no changes in SOM-positive cells were observed. The overall reduction of interneurons was verified by quantification of GAD67-immunoreactive cells (-24 A, in ErbB4-/- mice). The reduction of interneurons along the dorsoventral axis was more severe in intermediate and ventral portions than in the dorsal hippocampus, and regional reductions occurred in the CA1-3 regions and subiculum, whereas we found no significant changes in the dentate gyrus (DG). The expression by different populations of interneurons suggests that ErbB4 can modulate several microcircuits within the hippocampus and mediate the previously reported effects of NRG1 on network oscillations and synaptic plasticity. The selective reduction of GABAergic cells in ErbB4-/- mice is consistent with the role of NRG-ErbB4 signaling in the generation and migration of interneurons during development, and with neuronal and behavioral functional deficits in adult ErbB4 knockouts. (C) 2009 Wiley-Liss, Inc.(dagger) C1 [Neddens, Joerg; Buonanno, Andres] Eunice Shriver Kennedy NICHD, NIH, Mol Neurobiol Sect, Bethesda, MD 20892 USA. RP Neddens, J (reprint author), Eunice Shriver Kennedy NICHD, NIH, Mol Neurobiol Sect, 35 Lincoln Dr,Room 2C-1004, Bethesda, MD 20892 USA. FU National Institutes of Health, Eunice Shriver Kennedy NICHD FX Grant sponsors Intramural Research Program of the National Institutes of Health, Eunice Shriver Kennedy NICHD. NR 86 TC 55 Z9 56 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2010 VL 20 IS 6 BP 724 EP 744 DI 10.1002/hipo.20675 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 610FJ UT WOS:000278716500006 PM 19655320 ER PT J AU Shamy, JL Carpenter, DM Fong, SG Murray, EA Tang, CY Hof, PR Rapp, PR AF Shamy, J. L. Carpenter, D. M. Fong, S. G. Murray, E. A. Tang, C. Y. Hof, P. R. Rapp, P. R. TI Alterations of White Matter Tracts Following Neurotoxic Hippocampal Lesions in Macaque Monkeys: A Diffusion Tensor Imaging Study SO HIPPOCAMPUS LA English DT Article DE hippocampus; rhesus monkey; memory; morphometry; neuropsychology ID RHESUS-MONKEYS; AXONAL DEGENERATION; RECOGNITION MEMORY; FORNIX TRANSECTION; PREFRONTAL CORTEX; EPISODIC MEMORY; SPINAL-CORD; AMNESIA; CONNECTIONS; IMPAIRMENT AB Diffusion tensor imaging (DTI) is a valuable tool for assessing presumptive white matter alterations in human disease and animal models. The current study used DTI to examine the effects of selective neurotoxic lesions of the hippocampus on major white matter tracts and anatomically related brain regions in macaque monkeys. Two years postlesion, structural MRI, and DTI sequences were acquired for each subject. Volumetric assessment revealed a substantial reduction in the size of the hippocampus in experimental subjects, averaging 72% relative to controls, without apparent damage to adjacent regions. DTI images were processed to yield measures of fractional anisotropy (FA), apparent diffusion coefficient (ADC), parallel diffusivity (IADC), and perpendicular diffusivity (tADC), as well as directional color maps. To evaluate potential changes in major projection systems, a region of interest (ROI) analysis was conducted including the corpus callosum, fornix, temporal stem, cingulum bundle, ventromedial prefrontal white matter, and optic radiations. Lesion-related abnormalities in the integrity of the fiber tracts examined were limited to known hippocampal circuitry, including the fornix and ventromedial prefrontal white matter. These findings are consistent with the notion that hippocampal damage results in altered interactions with multiple memory-related brain regions, including portions of the prefrontal cortex. (C) 2010 Wiley-Liss, Inc. C1 [Rapp, P. R.] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Shamy, J. L.; Fong, S. G.; Hof, P. R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Murray, E. A.] Mt Sinai Sch Med, Dept Radiol, New York, NY USA. [Tang, C. Y.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Rapp, P. R.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Rapp, PR (reprint author), NIA, Lab Expt Gerontol, NIH, 251 Bayview Blvd,Suite 100,Rm 09C224, Baltimore, MD 21224 USA. EM rappp@mail.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 FU NIH [AG10606, MH62448, MH58911]; NIA; NIMH FX Grant sponsor: NIH; Grant numbers: AG10606, MH62448, MH58911; Grant sponsor: Intramural Research Programs of the NIA and NIMH. NR 25 TC 14 Z9 14 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2010 VL 20 IS 8 BP 906 EP 910 DI 10.1002/hipo.20737 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 636MF UT WOS:000280739300004 PM 20095006 ER PT S AU Falus, A Pos, Z Darvas, Z AF Falus, Andras Pos, Zoltan Darvas, Zsuzsanna BE Thurmond, RL TI Histamine in Normal and Malignant Cell Proliferation SO HISTAMINE IN INFLAMMATION SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID GROWTH-FACTOR PRODUCTION; RAT OXYNTIC MUCOSA; HISTIDINE-DECARBOXYLASE; MAST-CELLS; EXPERIMENTAL TUMOR; COLORECTAL-CANCER; H-2 RECEPTORS; ENDOGENOUS HISTAMINE; CYTOKINE EXPRESSION; MAMMARY CARCINOMAS AB Histamine is a biogenic amine widely distributed throughout the body. Given the observations that histamine can be induced and made available in an unstored diffusible form in tissues undergoing rapid growth (such as tumors and regenerating liver), it could have a role beyond inflammatory and allergic responses. C1 [Falus, Andras; Pos, Zoltan; Darvas, Zsuzsanna] Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1089 Budapest, Hungary. [Falus, Andras] Semmelweis Univ, Hungarian Acad Sci, Res Grp Inflammat Biol & Immunogenom, H-1089 Budapest, Hungary. [Pos, Zoltan] NIH, Dept Transfus Med, Infect Dis & Immunogenet Sect, Ctr Clin, Bethesda, MD 20892 USA. RP Falus, A (reprint author), Semmelweis Univ, Dept Genet Cell & Immunobiol, Nagyvarad Ter 4, H-1089 Budapest, Hungary. EM faland@dgci.sote.hu RI Pos, Zoltan/C-3623-2014 OI Pos, Zoltan/0000-0002-2574-7616 NR 73 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-8055-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 709 BP 109 EP 123 D2 10.1007/978-1-4419-8056-4 PG 15 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BSR23 UT WOS:000285533400011 PM 21618892 ER PT S AU Chung, JY Hewitt, SM AF Chung, Joon-Yong Hewitt, Stephen M. BA Darby, IA BF Darby, IA BE Hewitson, TD TI An Optimized RNA Extraction Method from Archival Formalin-Fixed Paraffin-Embedded Tissue SO HISTOLOGY PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Formalin-fixed; paraffin-embedded; tissue; RNA isolation; RT-PCR ID EXPRESSION ANALYSIS; AMPLIFICATION; EXPERIENCE; RECOVERY; GENE; PCR AB Formalin-fixed and paraffin-embedded (FFPE) tissue is one of the most valuable resources available for molecular biological analysis oil tissue after diagnostic histopathological examination. Gene expression profiles of FFPE can provide insights into molecular mechanisms of disease but are difficult due to the high level of cross-linking of biomolecules by formalin fixation. Despite advances in molecular technologies, the quality of RNA obtained from FFPE tissue remains variable. We have optimized a reliable RNA extraction method for FFPE tissue. This approach is based oil deparaffinization at high temperature coupled with a 3-day lysis at 65 degrees C. The average total RNA yield is 4.5-5.5 ng per 1 mm(3) of archival FFPE tissue and 260/280 ratios are between 1.80 and 1.95. The extracted RNA has a modal fragment length between 100 and 200 nucleotides by bioanalyzer analysis. Although modal lengths of RNA fragments were shorter, reverse transcription and polymerase chain reaction was able to amplify amplicons in the range of 300 base pairs. This optimized method improves the utility of FFPE tissue for molecular profiling studies. C1 [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Chung, JY (reprint author), NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 NR 11 TC 9 Z9 9 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 978-1-60327-344-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 611 BP 19 EP 27 DI 10.1007/978-1-60327-345-9_2 D2 10.1007/978-1-60327-345-9 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BMR75 UT WOS:000273424900002 PM 19960319 ER PT B AU Mattson, MP Calabrese, EJ AF Mattson, Mark P. Calabrese, Edward J. BE Mattson, MP Calabrese, EJ TI Hormesis: What It Is and Why It Matters SO HORMESIS: A REVOLUTION IN BIOLOGY, TOXICOLOGY AND MEDICINE LA English DT Article; Book Chapter DE Adaptation; Biphasic; Environmental protection; Evolution; Preconditioning; Stress; Toxins ID NEURODEGENERATIVE DISORDERS; CALORIC RESTRICTION; SYNAPTIC PLASTICITY; OXIDATIVE STRESS; DOSE RESPONSES; FREE-RADICALS; DISEASE; RATS; BDNF; ACTIVATION AB Hormesis describes any process in which a cell, organism, or group of organisms exhibits a biphasic response to exposure to increasing amounts of a substance or condition (e.g., chemical, sensory stimulus, or metabolic stress); typically, low-dose exposures elicit a stimulatory or beneficial response, whereas high doses cause inhibition or toxicity. The biphasic dose-response signature of hormesis is a common result of experiments in the field of toxicology, but the low-dose data have been largely ignored, and the prevailing view is that it is important to reduce levels of toxins as much as possible. However, in many cases, the "toxins" actually have essential or beneficial effects in low amounts. Prominent examples of such beneficial "toxins" are trace metals such as selenium, chromium, and zinc. Fundamental inter- and intracellular signals also exhibit hormetic dose responses, including hormones, neurotransmitters, growth factors, calcium, and protein kinases. Moreover, everyday health-promoting lifestyle factors, including exercise and dietary energy restriction, act, at least in part, through hormetic mechanisms involving activation of adaptive cellular stress response pathways (ACSRPs). ACSRPs typically involve receptors coupled to kinases and activation of transcription factors that induce the expression of cytoprotective proteins such as antioxidant enzymes, protein chaperones, and growth factors. The recognition and experimental utilization of hormesis cad to novel approaches for preventing and treating a range of diseases, including cancers, cardiovascular disease, and neurodegenerative disorders. C1 [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Calabrese, Edward J.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Environm Hlth Sci, Amherst, MA 01003 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov; edwardc@schoolph.umass.edu; mattsonm@grc.nia.nih.gov; edwardc@schoolph.umass.edu NR 50 TC 15 Z9 16 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-494-4 PY 2010 BP 1 EP 13 DI 10.1007/978-1-60761-495-1_1 D2 10.1007/978-1-60761-495-1 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA BMT76 UT WOS:000273557700001 ER PT B AU Mattson, MP AF Mattson, Mark P. BE Mattson, MP Calabrese, EJ TI The Fundamental Role of Hormesis in Evolution SO HORMESIS: A REVOLUTION IN BIOLOGY, TOXICOLOGY AND MEDICINE LA English DT Article; Book Chapter DE Competition; Darwin; Ecology; Natural selection; Selenium; Stress resistance; Survival ID NEUROTROPHIC FACTOR BDNF; NF-KAPPA-B; NEURODEGENERATIVE DISORDERS; INSULIN SENSITIVITY; STRESS-RESPONSE; DOSE RESPONSES; BRAIN; MECHANISMS; EXERCISE; IRON AB Hormesis can be considered a major mechanism underlying Darwin's and Wallace's theory of evolution by natural selection. The ability of organisms to respond adaptively to low levels of exposure to environmental hazards in a manner that increases their resistance to more severe similar or different hazards is fundamental to the evolutionary process. The organisms that survive and reproduce are those best able to tolerate or avoid environmental hazards while competing successfully for limited energy (food) resources. Therefore many of the genes selected for their survival value encode proteins that protect cells against stress (heat-shock proteins, antioxidant enzymes, antiapoptotic proteins, etc.) or that mediate behavioral responses to environmental stressors (neurotransmitters, hormones, muscle cell growth factors, etc.). Examples of environmental conditions that can, at subtoxic levels, activate hormetic responses and examples of the genes and cellular and molecular pathways that mediate such adaptive stress responses are provided to illustrate how hormesis mediates natural selection. C1 NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov NR 56 TC 2 Z9 3 U1 2 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-494-4 PY 2010 BP 57 EP 68 DI 10.1007/978-1-60761-495-1_3 D2 10.1007/978-1-60761-495-1 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA BMT76 UT WOS:000273557700003 ER PT B AU Son, TG Cutler, RG Mattson, MP Camandola, S AF Son, Tae Gen Cutler, Roy G. Mattson, Mark P. Camandola, Simonetta BE Mattson, MP Calabrese, EJ TI Transcriptional Mediators of Cellular Hormesis SO HORMESIS: A REVOLUTION IN BIOLOGY, TOXICOLOGY AND MEDICINE LA English DT Article; Book Chapter DE Transcription factors; Hormesis; Exercise; Calorie restriction; Phytochemicals; HSF; Nrf2; FOXO; NF-kappa B ID NF-KAPPA-B; HEAT-SHOCK FACTOR-1; RAT SKELETAL-MUSCLE; EXTENDS LIFE-SPAN; DISMUTASE GENE-EXPRESSION; HEME OXYGENASE-1 GENE; PANCREATIC BETA-CELLS; OXIDATIVE-STRESS; C-ELEGANS; PHOSPHATIDYLINOSITOL 3-KINASE/AKT AB Hormesis is the beneficial adaptive response of cells and organisms to acute subtoxic doses of certain types of environmental stressors (e.g., heat, oxidation, environmental toxins). Repetitive hormesis through routine exercise, calorie restriction, or ingestion of low levels of phytotoxins with the diet can stimulate cellular catabolic turnover of damaged molecules and increase protective mechanisms. The net result is an improved ability of the organism to better cope with noxious insults (i.e., preconditioning). Key to the benefits of hormesis are (1) the intensity of the stress/toxin, which needs to be enough to stimulate an effective response without causing permanent damage (i.e., subtoxic) and (2) the duration of the exposure, which needs to be limited (acute) to allow repair and recovery. Fundamental to the hormetic adaptive response is gene expression regulation. Although different stressors elicit unique signature responses, the comparison of prototypical hormetic inducers has highlighted the role played by a few transcription factor families. The periodic pulsatile activation of Nrf2, NF-kappa B, HSF, and FOXO has been found to be essential to obtaining the beneficial effects of various hormetic stimuli in different biolocyical models. This chapter discusses molecular mechanisms and gene targets for these transcription factor families in the hormetic adaptive context. C1 [Son, Tae Gen; Cutler, Roy G.; Mattson, Mark P.; Camandola, Simonetta] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Son, TG (reprint author), NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. EM sont2@grc.nia.nih.gov; cutlerro@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov; camandolasi@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov NR 156 TC 3 Z9 4 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-494-4 PY 2010 BP 69 EP 93 DI 10.1007/978-1-60761-495-1_4 D2 10.1007/978-1-60761-495-1 PG 25 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA BMT76 UT WOS:000273557700004 ER PT B AU Chadwick, W Maudsley, S AF Chadwick, Wayne Maudsley, Stuart BE Mattson, MP Calabrese, EJ TI The Devil Is in the Dose: Complexity of Receptor Systems and Responses SO HORMESIS: A REVOLUTION IN BIOLOGY, TOXICOLOGY AND MEDICINE LA English DT Article; Book Chapter DE G protein-coupled receptor; Dose response; Allosteric; Conformation; Environment; Flavor; Receptive ID PROTEIN-COUPLED RECEPTORS; GROWTH-FACTOR RECEPTOR; BETA(1)-ADRENERGIC RECEPTORS; BETA(2)-ADRENERGIC RECEPTOR; ALLOSTERIC MODULATION; MUSCARINIC RECEPTORS; ADRENERGIC-RECEPTOR; EFFECTOR PATHWAY; OPIOID RECEPTORS; ACTIVATION AB Through evolutionary history the primary mechanism by which the cells or tissues of most organisms sense their environment has been the heptahelical G protein-coupled receptor (GPCR). This prototypic receptive entity has its origins in the earliest forms of life and often comprises up to 5% of the genome of most unicellular and multicellular life forms. The GPCR system has adapted to perceive almost all forms of environmental entities, for example, photons, odorants, lipids, carbohydrates, peptides, and nucleic acids. The GPCR system has also likely adapted to the presence of exogenous compounds that may at some doses be deleterious but at lower levels may indeed possess beneficial actions. Therefore, with respect to the evolutionary pressure of diverse environments, it would be an extreme advantage for an organism to adapt multiple components of its primary receptive system to take advantage of any beneficial effects of agents present in harsh or damaging environments. C1 [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Neurosci Lab, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. EM chadwickwa@nia.nih.gov; maudsleyst@grc.nia.nih.gov NR 62 TC 5 Z9 7 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-494-4 PY 2010 BP 95 EP 108 DI 10.1007/978-1-60761-495-1_5 D2 10.1007/978-1-60761-495-1 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA BMT76 UT WOS:000273557700005 ER PT B AU Stranahan, AM Mattson, MP AF Stranahan, Alexis M. Mattson, Mark P. BE Mattson, MP Calabrese, EJ TI Exercise-Induced Hormesis SO HORMESIS: A REVOLUTION IN BIOLOGY, TOXICOLOGY AND MEDICINE LA English DT Article; Book Chapter DE Running; Exercise; Wheel; Treadmill; Hippocampus ID OAT BETA-GLUCAN; GROWTH-FACTOR-I; MODERATE EXERCISE; CELL-PROLIFERATION; VOLUNTARY EXERCISE; PHYSICAL-EXERCISE; OXIDATIVE STRESS; DENTATE GYRUS; RESPIRATORY-INFECTION; CYTOKINE RESPONSE AB The consequences of physical activity on the brain can readily be integrated into a hormetic framework. Whereas low- to moderate-intensity exercise exerts positive effects on the body, excessive exercise can be detrimental for somatic health. Here we review the evidence linking physical activity with cellular and functional modifications in different organ systems, with a focus on the dose-response characteristics of this relationship. Voluntary running and short-term treadmill running within the range of intensities normally experienced during voluntary running both enhance metabolism and preserve function across multiple organ systems. In contrast, running to exhaustion has a negative impact on global functioning. Overall, the effects of exercise clearly depend on the amount and intensity of activity. These effects conform to the biological principle of hormesis. 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, Baltimore, MD 21218 USA. EM alexis.stranahan@jhu.edu; mattsonm@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov NR 77 TC 1 Z9 1 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-494-4 PY 2010 BP 109 EP 122 DI 10.1007/978-1-60761-495-1_6 D2 10.1007/978-1-60761-495-1 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA BMT76 UT WOS:000273557700006 ER PT B AU Martin, B Ji, SG White, CM Maudsley, S Mattson, MP AF Martin, Bronwen Ji, Sunggoan White, Caitlin M. Maudsley, Stuart Mattson, Mark P. BE Mattson, MP Calabrese, EJ TI Dietary Energy Intake, Hormesis, and Health SO HORMESIS: A REVOLUTION IN BIOLOGY, TOXICOLOGY AND MEDICINE LA English DT Article; Book Chapter DE Caloric restriction; Energy homeostasis; Endocrinological; Neuroprotective; Adaptive; Evolutionary ID ACTIVATED-RECEPTOR-ALPHA; PROTECTS HIPPOCAMPAL-NEURONS; TRANSCRIPTION FACTOR FOXO3A; FATTY-ACID OXIDATION; CALORIC RESTRICTION; GENE-EXPRESSION; LIFE-SPAN; CAENORHABDITIS-ELEGANS; SKELETAL-MUSCLE; RHESUS-MONKEYS AB The ability to adapt to varying levels of available energy in the form of food in the environment has allowed species to propagate and also thrive during of energy surplus. However, in times when there is scant food available, similar evolutionary pressures have ensured that physiological systems can adapt to and utilize this food scarcity to their advantage. Considerable research has demonstrated that upon reduction of food intake, there are several beneficial effects upon cardiovascular, endocrinological, immune, and neuronal systems. Some of the effects of caloric restriction, however, tend to be exaggerated in many experimental cases due to biasing of overweight control subjects, yet reduction of total body weight still seems to engender beneficial effects for the individual. Some of the beneficial effects of caloric restriction are believed to arise from a reflexive response to the "stress" of reduced food intake. In conjunction with this is a similar hypothesis, known as "hormesis," which proposes in a similar vein that other forms of stress, such as toxicological stress, can also engender a "protective" set of physiological responses that shields the individual from further stresses. This chapter discusses how these two theories of protective responses-caloric restriction and hormesis-share many overlapping properties. C1 [Martin, Bronwen] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [Ji, Sunggoan; White, Caitlin M.; Maudsley, Stuart; Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Martin, B (reprint author), NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. EM martinbro@mail.nih.gov; jis2@mail.nih.gov; whitecm2@mail.nih.gov; maudsleyst@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov NR 93 TC 1 Z9 1 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-494-4 PY 2010 BP 123 EP 137 DI 10.1007/978-1-60761-495-1_7 D2 10.1007/978-1-60761-495-1 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA BMT76 UT WOS:000273557700007 ER PT B AU Mattson, MP Stranahan, A Martin, B AF Mattson, Mark P. Stranahan, Alexis Martin, Bronwen BE Mattson, MP Calabrese, EJ TI Couch Potato: The Antithesis of Hormesis SO HORMESIS: A REVOLUTION IN BIOLOGY, TOXICOLOGY AND MEDICINE LA English DT Article; Book Chapter DE Calories; Diabetes; Exercise; Food addiction; Insulin resistance; Obesity; Sedentary lifestyle ID ACTIVATED PROTEIN-KINASE; GLUCAGON-LIKE PEPTIDE-1; CALORIC RESTRICTION; ALZHEIMERS-DISEASE; DIETARY RESTRICTION; PHYSICAL-ACTIVITY; OXIDATIVE STRESS; SKELETAL-MUSCLE; ENVIRONMENTAL ENRICHMENT; DOPAMINERGIC-NEURONS AB The impact of hormesis on health can be further appreciated by consideration of the "couch potato" lifestyle. When cells in the body and brain are not challenged, they become complacent and are therefore Vulnerable to injury and disease. Lack of physical and mental exercise, in combination with excessive food intake. results in a condition called insulin resistance that is a harbinger of, diabetes and cardiovascular disease. Oil the other hand, when fewer calories are consumed and when more energy is expended (exercise), cells are subjected to a mild metabolic stress. They respond to this mild stress adaptively by increasing their ability to take up glucose in respond to insulin. This hormesis response is, in part, responsible for the ability of dietary energy restriction and exercise to ward off diabetes and cardiovascular disease. However, obesity and diabetes are not the only adverse physiological consequences of being a "couch potato." Exercise and dietary energy restriction improve the functional efficiency of the heart and gut through a hormetic mechanism that involves increased activity of the parasympathetic component of the autonomic nervous system. As a consequence, heart rate and blood pressure are decreased and Out motility is increased, thereby reducing the risk of heart disease, stroke, and colon cancer. Relatively underappreciated is the contribution of the lack of mental challenges to the poor health associated with the couch potato lifestyle. Individuals who en-age in intellectually challenging occupations or hobbies may be at reduced risk for Alzheimer's disease because of the beneficial stress imposed on the neurons when they are challenged. Studies have shown that neurons respond to mental and physical activity by increasing their production of neurotrophic factors" that may help them to resist disorders such as Alzheimer's disease and Parkinson's disease. C1 [Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. [Martin, Bronwen] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [Stranahan, Alexis] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov; alexis.stranahan@jhu.edu; martinbro@mail.nih.gov; mattsonm@grc.nia.nih.gov NR 77 TC 1 Z9 1 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-494-4 PY 2010 BP 139 EP 151 DI 10.1007/978-1-60761-495-1_8 D2 10.1007/978-1-60761-495-1 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA BMT76 UT WOS:000273557700008 ER PT B AU Calabrese, EJ Mattson, MP AF Calabrese, Edward J. Mattson, Mark P. BE Mattson, MP Calabrese, EJ TI The Hormetic Pharmacy: The Future of Natural Products and Man-Made Drugs in Disease Prevention and Treatment SO HORMESIS: A REVOLUTION IN BIOLOGY, TOXICOLOGY AND MEDICINE LA English DT Article; Book Chapter DE Antidepressants; Cardiovascular disease; Dietary supplements; Dose and frequency; Nutriceuticals; Pharmaceutical industry ID BIPHASIC DOSE RESPONSES; NEURAL PROGENITOR CELLS; SMOOTH-MUSCLE-CELLS; OXIDATIVE STRESS; CALORIE RESTRICTION; DIETARY RESTRICTION; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; IN-VITRO; HORMESIS AB This chapter proposes a new look at the modern pharmacy of natural products and man-made drugs. It shows that local pharmacies have been dispensing drugs based on hormesis for many decades. Among drugs that act via the hormetic dose response are those that combat anxiety and depression, make bones stronger, grow hair thicker, enhance cognitive function, and lessen pain. These drugs are some of the staples of the industry, permitting millions of people to live more normal and better lives. This chapter also shows that even when commonly used drugs such as antibiotics are administered to kill bacteria, they act hormetically at low doses and may be of concern because they can cause harmful bacterial colonies to grow. This is the case for antitumor drugs as well. Thus, the modern pharmacy is really a hormetic pharmacy, but this is really just the beginning. The currently unfolding future is one in which the biomedical and pharmaceutical giants will be developing so-called hormetic mimetics-drugs that can induce the normal adaptive pathways seen in the thousands of studies demonstrating hormesis but without exposing individuals to toxic doses of chemicals, ionizing radiation, extreme heat, or hard-to-maintain caloric restriction regimens. Screening chemicals based on their ability to activate, at subtoxic doses, specific adaptive cellular stress response pathways is a promising approach for drug development. The future pharmacy will be enhanced by research strategies and clinical practices that adopt hormetic principles and applications. C1 [Calabrese, Edward J.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Environm, Div Hlth Sci, Amherst, MA 01003 USA. [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Calabrese, EJ (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Environm, Div Hlth Sci, Amherst, MA 01003 USA. EM edwardc@schoolph.umass.edu; mattsonm@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov; edwardc@schoolph.umass.edu NR 59 TC 0 Z9 0 U1 2 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60761-494-4 PY 2010 BP 177 EP 198 DI 10.1007/978-1-60761-495-1_10 D2 10.1007/978-1-60761-495-1 PG 22 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA BMT76 UT WOS:000273557700010 ER PT J AU Andrade, AC Baron, J Manolagas, SC Shaw, NJ Rappold, GA Donaldson, MDC Gault, EJ Savendahl, L AF Andrade, Anenisia C. Baron, Jeffrey Manolagas, Stavros C. Shaw, Nick J. Rappold, Gudrun A. Donaldson, Malcolm D. C. Gault, Emma Jane Saevendahl, Lars TI Hormones and Genes of Importance in Bone Physiology and Their Influence on Bone Mineralization and Growth in Turner Syndrome SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Review DE Bone; Growth; Turner syndrome; SHOX; Wnt; Oxandrolone; Estrogen ID FORKHEAD-BOX-O; T-CELL-FACTOR; SHORT-STATURE; FINAL HEIGHT; SHOX HAPLOINSUFFICIENCY; OXIDATIVE STRESS; BETA-CATENIN; DENSITY; PLATE; FRACTURE AB This mini review summarizes papers presented in a Joint Symposium between the Bone, Growth Plate and Turner Syndrome Working Groups of the European Society for Paediatric Endocrinology (ESPE) that was held on September 9, 2009, in New York. The program had been composed to give an update on hormones and genes of importance in bone physiology and their influence on bone mineralization and growth in Turner syndrome. This paper summarizes the data and highlights the main topics and discussions related to each presentation. Copyright (C) 2010 S. Karger AG, Basel C1 [Andrade, Anenisia C.] Karolinska Inst, Pediat Endocrinol Unit, Dept Woman & Child Hlth, SE-17176 Stockholm, Sweden. [Baron, Jeffrey] NICHD, Sect Growth & Dev, NIH, Bethesda, MD USA. [Manolagas, Stavros C.] Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Little Rock, AR 72205 USA. [Manolagas, Stavros C.] Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. [Shaw, Nick J.] Birmingham Childrens Hosp, Dept Endocrinol, Birmingham, W Midlands, England. [Donaldson, Malcolm D. C.; Gault, Emma Jane] Royal Hosp Sick Children, Dept Child Hlth, Glasgow G3 8SJ, Strathclyde, Scotland. [Rappold, Gudrun A.] Univ Heidelberg, Dept Human Mol Genet, Heidelberg, Germany. RP Andrade, AC (reprint author), Karolinska Inst, Pediat Endocrinol Unit, Dept Woman & Child Hlth, Q2 08, SE-17176 Stockholm, Sweden. EM anenisia.andrade@ki.se OI Savendahl, Lars/0000-0003-1067-4976 FU BLRD VA [I01 BX001405] NR 31 TC 6 Z9 6 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2010 VL 73 IS 3 BP 161 EP 165 DI 10.1159/000284356 PG 5 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 586OL UT WOS:000276919900002 PM 20197667 ER PT B AU Zhang, SR Williamson, PR AF Zhang, Shirong Williamson, Peter R. BE Barton, AW TI THE ROLES OF HEAT SHOCK PROTEIN 70 IN MICROBIAL PATHOGENESIS' SO HOST-PATHOGEN INTERACTIONS: GENETICS, IMMUNOLOGY AND PHYSIOLOGY SE Immunology and Immune System Disorders LA English DT Article; Book Chapter DE Fungus; infection; pathogenesis; laccase; heat shock protein; protein secretion; virulence ID HEAT-SHOCK-PROTEIN; DNA-BINDING ACTIVITY; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; IN-VIVO; CRYPTOCOCCUS-NEOFORMANS; MOLECULAR CHAPERONES; HSP70 CHAPERONES; DENDRITIC CELLS; PARACOCCIDIOIDES-BRASILIENSIS AB Adaptation of pathogens to the stressful conditions of the mammalian host requires a rapid programmatic response to ensure survival. Recent evidence suggests that heat shock proteins play a dual role in both adaptation to the new environment, as well as the expression of virulence factors that cause host cell damage. For example, in the AIDS-related fungus, Cryptococcus neoformans, Hsp70 has been found to activate the transcription factor heat shock factor 1 by binding to upstream activating regions of a laccase gene, which encodes an immunomodulatory virulence factor. In addition, secretion of extracellular Hsp70 results in immunomodulatory effects mediated through interactions with mammalian receptors such as the chemokine receptor CCR5. To protect the integrity of the secreted protein, extracellular Hsp70 expression occurs within a specialized vesicle, the exosome, which surrounds the protein with a protective lipid membrane. The exosome secretory pathway is distinct from that producing cell wall and capsule and is dependent on formation of an unusual structure called the multivesicular body. This exosomal secretory pathway thus provides a protected pathway of protein secretion for Hsp70 that, in concert with the intracellular protein, serves to alter the host-pathogen relationship. C1 [Zhang, Shirong] Univ Illinois, Coll Med, Dept Med, Infect Dis Sect, Chicago, IL USA. [Williamson, Peter R.] NIAID, NIH, Bethesda, MD 20892 USA. RP Williamson, PR (reprint author), 9000 Rockville Pike,Bldg 10,Rm 11N234,MSC 1888, Bethesda, MD 20892 USA. EM williamsonpr@mail.nih.gov NR 101 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 978-1-60876-286-6 J9 IMMUNOL IMMUNE SYST PY 2010 BP 153 EP 171 PG 19 WC Immunology SC Immunology GA BPT70 UT WOS:000279878600007 ER PT J AU Ascoli, M Bahl, O Berger, P Bidart, JM Birken, S Boime, I Braunstein, G Canfield, R Chard, T Dufau, M Fiddes, J Hussa, R Iles, R Kobata, A Mann, K Nishimura, R Nisula, B Norman, R Odell, W Puett, D Rao, CV Ruddon, R Stenman, U Vaitukaitis, J Weintraub, B AF Ascoli, Mario Bahl, Om Berger, Peter Bidart, Jean-Michel Birken, Steven Boime, Irving Braunstein, Glenn Canfield, Robert Chard, Timothy Dufau, Maria Fiddes, John Hussa, Robert Iles, Ray Kobata, Akira Mann, Klauss Nishimura, Ryuichiro Nisula, Bruce Norman, Robert Odell, William Puett, David Rao, C. V. Ruddon, Raymond Stenman, Ulf Vaitukaitis, Judith Weintraub, Bruce BA Cole, LA Butler, SA BF Cole, LA Butler, SA TI Human Chorionic Gonadotropin (hCG) Foreword SO HUMAN CHORIONIC GONADOTROPIN (HCG) LA English DT Editorial Material; Book Chapter C1 [Ascoli, Mario] Univ Iowa, Iowa City, IA 52240 USA. [Bahl, Om] SUNY Buffalo, Buffalo, NY 14260 USA. [Berger, Peter] Austrian Acad Sci, Innsbruck, Austria. [Bidart, Jean-Michel] Inst Gustave Roussy, Villejuif, France. [Birken, Steven; Dufau, Maria; Nisula, Bruce; Vaitukaitis, Judith; Weintraub, Bruce] NIH, Bethesda, MD 20892 USA. [Boime, Irving] Washington Univ, St Louis, MO USA. [Braunstein, Glenn] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Canfield, Robert] Columbia Presbyterian Med Ctr, New York, NY USA. [Chard, Timothy] St Bartholomews Hosp, London, England. [Fiddes, John] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Hussa, Robert] Med Coll Wisconsin, Milwauke, WI USA. [Iles, Ray] Middlesex Univ, London N17 8HR, England. [Kobata, Akira] Univ Tokyo, Tokyo 1138654, Japan. [Mann, Klauss] Univ Essen Gesamthsch, Essen, Germany. [Nishimura, Ryuichiro] Hyogo Canc Ctr, Akashi, Hyogo, Japan. [Norman, Robert] Univ Adelaide, Adelaide, SA 5005, Australia. [Odell, William] Utah Med Ctr, Salt Lake City, UT USA. [Puett, David] Univ Georgia, Athens, GA 30602 USA. [Rao, C. V.] Univ Louisville, Louisville, KY 40292 USA. [Ruddon, Raymond] Univ Michigan, Ann Arbor, MI 48109 USA. [Stenman, Ulf] Univ Helsinki, FIN-00014 Helsinki, Finland. RP Ascoli, M (reprint author), Univ Iowa, Iowa City, IA 52240 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-384908-3 PY 2010 BP XI EP XIII PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BEO11 UT WOS:000317522100001 ER PT J AU Parikh, H Deng, ZM Yeager, M Boland, J Matthews, C Jia, JP Collins, I White, A Burdett, L Hutchinson, A Qi, LQ Bacior, JA Lonsberry, V Rodesch, MJ Jeddeloh, JA Albert, TJ Halvensleben, HA Harkins, TT Ahn, J Berndt, SI Chatterjee, N Hoover, R Thomas, G Hunter, DJ Hayes, RB Chanock, SJ Amundadottir, L AF Parikh, Hemang Deng, Zuoming Yeager, Meredith Boland, Joseph Matthews, Casey Jia, Jinping Collins, Irene White, Ariel Burdett, Laura Hutchinson, Amy Qi, Liqun Bacior, Jennifer A. Lonsberry, Victor Rodesch, Matthew J. Jeddeloh, Jeffrey A. Albert, Thomas J. Halvensleben, Heather A. Harkins, Timothy T. Ahn, Jiyoung Berndt, Sonja I. Chatterjee, Nilanjan Hoover, Robert Thomas, Gilles Hunter, David J. Hayes, Richard B. Chanock, Stephen J. Amundadottir, Laufey TI A comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33 SO HUMAN GENETICS LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; GENOME-WIDE ASSOCIATION; REGULATED ACTIVITY; UPSTREAM ENHANCER; SERINE-PROTEASE; CANCER; PROMOTER; RISK; EXPRESSION; MORTALITY AB Single nucleotide polymorphisms (SNPs) in the KLK3 gene on chromosome 19q13.33 are associated with serum prostate-specific antigen (PSA) levels. Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Since the KLK3 gene encodes the PSA protein that forms the basis for a widely used screening test for prostate cancer, it is critical to fully characterize genetic variation in this region and assess its relationship with the risk of prostate cancer. We have conducted a next-generation sequence analysis in 78 individuals of European ancestry to characterize common (minor allele frequency, MAF > 1%) genetic variation in a 56 kb region on chromosome 19q13.33 centered on the KLK3 gene (chr19:56,019,829-56,076,043 bps). We identified 555 polymorphic loci in the process including 116 novel SNPs and 182 novel insertion/deletion polymorphisms (indels). Based on tagging analysis, 144 loci are necessary to tag the region at an r (2) threshold of 0.8 and MAF of 1% or higher, while 86 loci are required to tag the region at an r (2) threshold of 0.8 and MAF > 5%. Our sequence data augments coverage by 35 and 78% as compared to variants in dbSNP and HapMap, respectively. We observed six non-synonymous amino acid or frame shift changes in the KLK3 gene and three changes in each of the neighboring genes, KLK15 and KLK2. Our study has generated a detailed map of common genetic variation in the genomic region surrounding the KLK3 gene, which should be useful for fine-mapping the association signal as well as determining the contribution of this locus to prostate cancer risk and/or regulation of PSA expression. C1 [Parikh, Hemang; Jia, Jinping; Collins, Irene; White, Ariel; Chanock, Stephen J.; Amundadottir, Laufey] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA. [Parikh, Hemang; Deng, Zuoming; Yeager, Meredith; Boland, Joseph; Matthews, Casey; Jia, Jinping; Collins, Irene; White, Ariel; Burdett, Laura; Hutchinson, Amy; Qi, Liqun; Bacior, Jennifer A.; Lonsberry, Victor; Ahn, Jiyoung; Berndt, Sonja I.; Chatterjee, Nilanjan; Hoover, Robert; Thomas, Gilles; Hayes, Richard B.; Chanock, Stephen J.; Amundadottir, Laufey] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Deng, Zuoming; Yeager, Meredith; Boland, Joseph; Matthews, Casey; Burdett, Laura; Hutchinson, Amy; Qi, Liqun; Bacior, Jennifer A.; Lonsberry, Victor] NCI Frederick, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21702 USA. [Rodesch, Matthew J.; Jeddeloh, Jeffrey A.; Albert, Thomas J.; Halvensleben, Heather A.] Roche NimbleGen, Madison, WI 53719 USA. [Harkins, Timothy T.] Roche Appl Sci, Indianapolis, IN 46250 USA. [Thomas, Gilles] Ctr Leon Berard, INSERM, U590, F-69373 Lyon 08, France. [Ahn, Jiyoung; Hayes, Richard B.] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY 10016 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. RP Amundadottir, L (reprint author), NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM amundadottirl@mail.nih.gov RI Amundadottir, Laufey/L-7656-2016; OI Amundadottir, Laufey/0000-0003-1859-8971; Hayes, Richard/0000-0002-0918-661X FU National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 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, commercial products or organizations imply endorsement by the US Government. NR 35 TC 17 Z9 17 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2010 VL 127 IS 1 BP 91 EP 99 DI 10.1007/s00439-009-0751-5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 533CF UT WOS:000272799100009 PM 19823874 ER PT J AU Shi, M Umbach, DM Weinberg, CR AF Shi, Min Umbach, David M. Weinberg, Clarice R. TI Testing Haplotype-Environment Interactions Using Case-Parent Triads SO HUMAN HEREDITY LA English DT Article DE Haplotype-environment interaction; Gene-environment interaction; Case-parent triad; Permutation test; Non-parametreic test; Population stratification ID GLUTATHIONE S-TRANSFERASES; CASE/PSEUDOCONTROL ANALYSIS; GENETIC ASSOCIATION; NUCLEAR FAMILIES; GENOTYPE; RISK AB Objective: Joint analysis of multiple SNP markers can be informative, but studying joint effects of haplotypes and environmental exposures is challenging. Population structure can involve both genes and exposures and a case-control study is susceptible to bias from either source of stratification. We propose a procedure that uses case-parent triad data and, though not fully robust, resists bias from population structure. Methods: Our procedure assumes that haplotypes under study have no influence on propensity to exposure. Then, under a no-interaction null hypothesis (multiplicative scale), transmission of a causative haplotype from parents to affected offspring might show distortion from Mendelian proportions but should be independent of exposure. We used this insight to develop a permutation test of no haplotype-by-exposure interaction. Results: Simulations showed that our proposed test respects the nominal Type I error rate and provides good power under a variety of scenarios. We illustrate by examining whether SNP variants in GSTP1 modify the association between maternal smoking and oral clefting. Conclusion: Our procedure offers desirable features: no need for haplotype estimation, validity under unspecified genetic main effects, tolerance to Hardy-Weinberg disequilibrium, ability to handle missing genotypes and a relatively large number of SNPs. Simulations suggest resistance to bias due to exposure-related population stratification. Copyright (C) 2010 S. Karger AG, Basel C1 [Shi, Min; Umbach, David M.; Weinberg, Clarice R.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, NIH, DHHS, Mail Drop A3-03 101-A315, Res Triangle Pk, NC 27709 USA. EM weinber2@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [Z01-ES040007, Z01-ES45002] FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES040007; Z01-ES45002). We thank Dr. Jeff Murray for sharing the clefting genotype data and Drs. Dana Hancock and Dmitri Zaykin for helpful comments on the manuscript. NR 19 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2010 VL 70 IS 1 BP 23 EP 33 DI 10.1159/000298326 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 619KC UT WOS:000279428100003 PM 20413979 ER PT J AU Aschard, H Hancock, DB London, SJ Kraft, P AF Aschard, Hugues Hancock, Dana B. London, Stephanie J. Kraft, Peter TI Genome-Wide Meta-Analysis of Joint Tests for Genetic and Gene-Environment Interaction Effects SO HUMAN HEREDITY LA English DT Article DE Gene-environment interaction; Genome-wide scan; Meta-analysis; Case-control association analysis; Complex disease ID ASSOCIATION; INDEPENDENCE; REGRESSION AB Background: There is growing interest in the study of gene-environment interactions in the context of genome-wide association studies (GWASs). These studies will likely require meta-analytic approaches to have sufficient power. Methods: We describe an approach for meta-analysis of a joint test for genetic main effects and gene-environment interaction effects. Using simulation studies based on a meta-analysis of five studies (total n = 10,161), we compare the power of this test to the meta-analysis of marginal test of genetic association and the meta-analysis of standard 1 d.f. interaction tests across a broad range of genetic main effects and gene-environment interaction effects. Results: We show that the joint meta-analysis is valid and can be more powerful than classical meta-analytic approaches, with a potential gain of power over 50% compared to the marginal test. The standard interaction test had less than 1% power in almost all the situations we considered. We also show that regardless of the test used, sample sizes far exceeding those of a typical individual GWAS will be needed to reliably detect genes with subtle gene-environment interaction patterns. Conclusion: The joint meta-analysis is an attractive approach to discover markers which may have been missed by initial GWASs focusing on marginal marker-trait associations. Copyright (C) 2011 S. Karger AG, Basel C1 [Aschard, Hugues] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Hancock, Dana B.; London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Aschard, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Bldg 2,Room 205,665 Huntington Ave, Boston, MA 02115 USA. EM haschard@hsph.harvard.edu RI Hancock, Dana/D-8577-2012; OI Hancock, Dana/0000-0003-2240-3604; London, Stephanie/0000-0003-4911-5290 FU Foundation Bettencourt-Schueller; National Institute of Environmental Health Sciences; [P01CA087969]; [5U01HG004399-02]; [HL35464]; [R21DK084529] FX We thank David Hunter, Frank Hu and Eric Rimm for use of the breast cancer, type 2 diabetes, and coronary heart disease data sets. These studies were supported by grants P01CA087969, 5U01HG004399-02 and HL35464, respectively. P.K. and H.A. were supported by R21DK084529, and H.A. received additional support from the Foundation Bettencourt-Schueller. Drs. S.J.L. and D.B.H. were supported by the Intramural Research Program of the National Institute of Environmental Health Sciences. NR 22 TC 19 Z9 19 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2010 VL 70 IS 4 BP 292 EP 300 DI 10.1159/000323318 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 725YK UT WOS:000287682600008 PM 21293137 ER PT J AU Li, QZ Zhang, H Yu, K AF Li, Qizhai Zhang, Hong Yu, Kai TI Approaches for Evaluating Rare Polymorphisms in Genetic Association Studies SO HUMAN HEREDITY LA English DT Article DE Association test; CDRV; Rare polymorphisms ID GENOME-WIDE ASSOCIATION; COLORECTAL ADENOMAS; VARIANTS; ALLELES; SUSCEPTIBILITY; CONTRIBUTE; DISEASES; CANCER; TABLE; RISK AB Most current genetic association studies, including genome-wide association studies, look for the single nucleotide polymorphisms (SNPs) with a relatively large minor allele frequency (MAF) (e.g. >5%) in the search for genetic loci underlying the susceptibility for complex diseases. The strategy of focusing on common SNPs in genetic association studies is very effective under the common-disease-common-variant (CDCV) hypothesis, which claims that common diseases are caused by common variants that have relatively small to moderate effects. Although the CDCV hypothesis has become the dogma guiding the conduct of association studies over the past decade, growing evidence from recent empirical data and simulations suggests that the causal genetic polymorphisms, including SNPs and copy number variants (CNVs), for common diseases have a wide spectrum of MAFs, ranging from rare to common. Unlike the analysis for common genetic variants, statistical approaches for the analysis of rare variants receive very little attention. Methods developed for common variants usually rely on their asymptotic properties, which can be inaccurate for the study of the rare variants with limited sample size. Although Fisher's exact test can be used for such a scenario, it is usually conservative and thus its usefulness is diminished to some extent. Here we propose two novel approaches for the analysis of rare genetic variants. Simulation studies and two real examples demonstrate the advantages of the proposed methods over the existing methods. Copyright (C) 2010 S. Karger AG, Basel C1 [Zhang, Hong; Yu, Kai] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing, Peoples R China. RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM yuka@mail.nih.gov FU National Institutes of Health; National Young Science Foundation of China [10901155] FX We would like to thank the editor and two anonymous reviewers for their insightful comments. We thank B.J. Stone for her valuable suggestions. H. Zhang and K. Yu are supported by the Intramural Program of the National Institutes of Health. Q. Li is partially supported by the National Young Science Foundation of China. No. 10901155. The opinions expressed in the article are not necessarily those of the National Institutes of Health. NR 20 TC 11 Z9 12 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2010 VL 69 IS 4 BP 219 EP 228 DI 10.1159/000291927 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 591EE UT WOS:000277281200001 PM 20332646 ER PT J AU Augusto, DG Pincerati, MR Martin, MP Carrington, M Petzl-Erler, ML AF Augusto, Danillo G. Pincerati, Marcia R. Martin, Maureen P. Carrington, Mary Petzl-Erler, Maria Luiza TI ALLELIC DIVERSITY OF KIR2DL4 AND KIR3DL2 IN THE POPULATION OF CURITIBA, BRAZIL. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY SEP 26-30, 2010 CL Hollywood, FL SP Amer Soc Histocompatibil & Immunogenet C1 [Augusto, Danillo G.; Petzl-Erler, Maria Luiza] Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. [Pincerati, Marcia R.] Univ Sao Paulo, BR-09500900 Sao Paulo, SP, Brazil. [Martin, Maureen P.; Carrington, Mary] NCI, NIH, Frederick, MD 21701 USA. RI Augusto, Danillo/F-3147-2013; Petzl-Erler, Maria-Luiza/H-8221-2012 OI Petzl-Erler, Maria-Luiza/0000-0002-0345-5276 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2010 VL 71 SU 1 BP S72 EP S72 PG 1 WC Immunology SC Immunology GA 654HE UT WOS:000282158300108 ER PT J AU Ghosh, AK Murga-Zamalloa, CA Chan, L Hitchcock, PF Swaroop, A Khanna, H AF Ghosh, Amiya K. Murga-Zamalloa, Carlos A. Chan, Lansze Hitchcock, Peter F. Swaroop, Anand Khanna, Hemant TI Human retinopathy-associated ciliary protein retinitis pigmentosa GTPase regulator mediates cilia-dependent vertebrate development SO HUMAN MOLECULAR GENETICS LA English DT Article ID BARDET-BIEDL-SYNDROME; GUANINE-NUCLEOTIDE-EXCHANGE; LEBER CONGENITAL AMAUROSIS; RETINAL DEGENERATION; MUTATION ANALYSIS; JOUBERT-SYNDROME; RPGR MUTATIONS; CENTROSOMAL PROTEIN; CONNECTING CILIUM; KUPFFERS VESICLE AB Dysfunction of primary cilia is associated with tissue-specific or syndromic disorders. RPGR is a ciliary protein, mutations in which can lead to retinitis pigmentosa (RP), cone-rod degeneration, respiratory infections and hearing disorders. Though RPGR is implicated in ciliary transport, the pathogenicity of RPGR mutations and the mechanism of underlying phenotypic heterogeneity are still unclear. Here we have utilized genetic rescue studies in zebrafish to elucidate the effect of human disease-associated mutations on its function. We show that rpgr is expressed predominantly in the retina, brain and gut of zebrafish. In the retina, RPGR primarily localizes to the sensory cilium of photoreceptors. Antisense morpholino (MO)-mediated knockdown of rpgr function in zebrafish results in reduced length of Kupffer's vesicle (KV) cilia and is associated with ciliary anomalies including shortened body-axis, kinked tail, hydrocephaly and edema but does not affect retinal development. These phenotypes can be rescued by wild-type (WT) human RPGR. Several of the RPGR mutants can also reverse the MO-induced phenotype, suggesting their potential hypomorphic function. Notably, selected RPGR mutations observed in XLRP (T99N, E589X) or syndromic RP (T124fs, K190fs and L280fs) do not completely rescue the rpgr-MO phenotype, indicating a more deleterious effect of the mutation on the function of RPGR. We propose that RPGR is involved in cilia-dependent cascades during development in zebrafish. Our studies provide evidence for a heterogenic effect of the disease-causing mutations on the function of RPGR. C1 [Ghosh, Amiya K.; Murga-Zamalloa, Carlos A.; Chan, Lansze; Hitchcock, Peter F.; Khanna, Hemant] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. [Swaroop, Anand] NEI, N NRL, NIH, Bethesda, MD 20892 USA. RP Khanna, H (reprint author), Univ Michigan, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM hkhanna@umich.edu OI Swaroop, Anand/0000-0002-1975-1141; Hitchcock, Peter/0000-0001-9454-2684 FU National Institutes of Health [RO1-EY007961, R01-EY07060]; Morphology Core of the Michigan Diabetes Research and Training Center [NIH5P60 DK20572]; Vision Core Facilities [EY07003] FX This work is supported by NEI intramural funds and grants from the National Institutes of Health (grant numbers RO1-EY007961 and R01-EY07060); Midwest Eye Banks and Transplantation Center and Foundation Fighting Blindness. This work also utilized the services provided by the Morphology Core of the Michigan Diabetes Research and Training Center (NIH5P60 DK20572) and of the Vision Core Facilities (EY07003). NR 63 TC 31 Z9 31 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2010 VL 19 IS 1 BP 90 EP 98 DI 10.1093/hmg/ddp469 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 531RV UT WOS:000272686700008 PM 19815619 ER PT J AU Marrone, GF Paulpillai, M Evans, RJ Singleton, EG Heishman, SJ AF Marrone, Gina F. Paulpillai, Mane Evans, Rebecca J. Singleton, Edward G. Heishman, Stephen J. TI Breath carbon monoxide and semiquantitative saliva cotinine as biomarkers for smoking SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE cigarette smoking; nicotine; cotinine; carbon monoxide; biomarker ID IMMUNOASSAY TEST STRIPS; NICOTINE DEPENDENCE; PLASMA COTININE; SMOKERS; ABSTINENCE; ADULTS AB Objective As a biomarker of smoking, semiquantitative analysis of cotinine (NicAlert(R)) offers several advantages over breath carbon monoxide (CO) and quantitative analysis of cotinine. Recent studies have used urine NicAlert(R) and breath CO in combination to verify abstinence. However, no studies have evaluated the performance of saliva NicAlert(R) against or in combination with breath CO. Method Breath CO, saliva NicAlert(R), and smoking history were compared in an urban population of daily smokers (n = 24) and nonsmokers (n = 25). Results Saliva NicAlert(R) predicted self-reported smoking with 100% sensitivity and 96% specificity. At a cutoff of > 5 ppm, breath CO had 100% sensitivity and 100% specificity in predicting self-reported smoking. Breath CO was positively correlated with saliva NicAlert(R) and negatively correlated with minutes since last cigarette. Conclusion Saliva NicAlert(R) had high sensitivity and specificity in identifying daily smokers. Compared to saliva NicAlert(R), breath CO level was more indicative of recent smoking. Future treatment studies should evaluate the performance of saliva NicAlert(R) as an alternative to the urine test. Published in 2009 by John Wiley & Sons, Ltd. C1 [Marrone, Gina F.; Paulpillai, Mane; Evans, Rebecca J.; Singleton, Edward G.; Heishman, Stephen J.] NIDA, Intramural Res Program, Nicotine Psychopharmacol Sect, Baltimore, MD 21224 USA. RP Heishman, SJ (reprint author), NIDA, Intramural Res Program, Nicotine Psychopharmacol Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM heishman@nih.gov OI Singleton, Edward G./0000-0003-3442-877X FU NIH, National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. The authors have no conflicts of interest. NR 18 TC 21 Z9 21 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD JAN PY 2010 VL 25 IS 1 BP 80 EP 83 DI 10.1002/hup.1078 PG 4 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 559DR UT WOS:000274802100009 PM 19998321 ER PT J AU Stacey, RB Bertoni, AG Eng, J Bluemke, DA Hundley, WG Herrington, D AF Stacey, R. Brandon Bertoni, Alain G. Eng, John Bluemke, David A. Hundley, W. Gregory Herrington, David TI Modification of the Effect of Glycemic Status on Aortic Distensibility by Age in the Multi-Ethnic Study of Atherosclerosis SO HYPERTENSION LA English DT Article DE aging; aorta; diabetes mellitus; glucose; MRI ID IMPAIRED FASTING GLUCOSE; DIASTOLIC HEART-FAILURE; PULSE-WAVE VELOCITY; CARDIOVASCULAR-DISEASE; ADVANCED GLYCOSYLATION; ESSENTIAL-HYPERTENSION; DIABETES-MELLITUS; COLLAGEN; ELASTIN; GLYCATION AB Elevated serum glucose from diabetes mellitus (DM) or impaired fasting glucose shares many mechanisms with aging that decrease aortic distensibility (AD), such as glycation of the extracellular matrix. However, few data compare the simultaneous effects of elevated serum glucose and aging on AD. To study this, we examined the relationship among fasting glucose status, age, and AD in the Multi-Ethnic Study of Atherosclerosis: a multiethnic cohort of individuals aged 45 to 84 years without clinical cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis, participants with normal fasting glucose (n=2270), impaired fasting glucose (n=870), and DM (n=412) underwent MRI assessment of proximal thoracic aortic distensibility. This sample was 46% male, 42% white, 30% black, 11% Asian, and 17% Hispanic. The relationship among glucose status, age, and AD was analyzed with general linear models by adjusting for factors influential on AD. An interaction term was used to determine whether age modified the effect of glucose status on AD. AD was lowest among those with DM. The interaction term was significant (P=0.024). Comparing participants <65 years of age, AD was different between normal fasting glucose and DM (P<0.01) and between normal fasting glucose and impaired fasting glucose (P=0.02). In those >65 years of age, the fasting glucose group was no longer a significant predictor of AD. Our data indicate that there are overall differences in AD among DM, impaired fasting glucose, and normal fasting glucose. However, age modified the effect of glucose status such that differences between the groups diminished with advancing age. (Hypertension. 2010;55:26-32.) C1 [Stacey, R. Brandon; Bertoni, Alain G.] Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Stacey, R. Brandon; Hundley, W. Gregory; Herrington, David] Wake Forest Univ, Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27109 USA. [Eng, John] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RP Stacey, RB (reprint author), Wake Forest Univ Hlth Sci, Cardiol Sect, Winston Salem, NC 27157 USA. EM bstacey@wfubmc.edu OI Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health [R01HL076438, HL076132]; National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169] FX This research was supported in part by National Institutes of Health grant R01HL076438 and National Institutes of Health T32 grant HL076132. This research was also supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 42 TC 22 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2010 VL 55 IS 1 BP 26 EP 32 DI 10.1161/HYPERTENSIONAHA.109.134031 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 533GW UT WOS:000272812700007 PM 19933927 ER PT J AU Gammill, HS Powers, RW Clifton, RG Van Dorsten, JP Klebanoff, MA Lindheimer, MD Sibai, B Landon, MB Miodovnik, M Dombrowski, M AF Gammill, Hilary S. Powers, Robert W. Clifton, Rebecca G. Van Dorsten, J. Peter Klebanoff, Mark A. Lindheimer, Marshall D. Sibai, Baha Landon, Mark B. Miodovnik, Menachem Dombrowski, Mitchell CA Eunice Kennedy Shriver Natl Inst C TI Does C-Reactive Protein Predict Recurrent Preeclampsia? SO HYPERTENSION IN PREGNANCY LA English DT Article DE Pregnancy; Preeclampsia; C Reactive protein Inflammation; Acute phase reaction ID LONG-TERM MORTALITY; INFLAMMATORY CYTOKINES; NEUTROPHIL ACTIVATION; PREGNANT-WOMEN; POTENTIAL ROLE; RISK; PARAMETERS; TRIMESTER; HISTORY; DISEASE AB Objective Evaluate association of the inflammatory marker C reactive protein with recurrent preeclampsia Methods Serum samples collected longitudinally in women with previous preeclampsia from the Maternal Fetal Medicine Units Network trial of aspirin to prevent preeclampsia were assayed for CRP Results Of 255 women studied, 50 developed recurrence Baseline C reactive protein concentration was similar between women who did and did not recur After adjusting for confounders, neither elevated baseline C reactive protein nor its change over gestation was associated with recurrence Conclusion In this group of women with previous preeclampsia, neither baseline C reactive protein concentration nor change in concentration over gestation was associated with recurrent preeclampsia C1 [Gammill, Hilary S.; Powers, Robert W.] Univ Pittsburgh, Dept Obstet, Pittsburgh, PA USA. [Gammill, Hilary S.; Powers, Robert W.] Univ Pittsburgh, Dept Gynecol, Pittsburgh, PA USA. [Clifton, Rebecca G.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Van Dorsten, J. Peter] Med Univ S Carolina, Charleston, SC 29425 USA. [Klebanoff, Mark A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Lindheimer, Marshall D.] Univ Chicago, Chicago, IL 60637 USA. [Sibai, Baha] Univ Tennessee, Memphis, TN USA. [Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA. [Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA. [Dombrowski, Mitchell] Wayne State Univ, Detroit, MI USA. RP Gammill, HS (reprint author), Univ Washington, Dept Obstet & Gynecol, Box 356460, Seattle, WA 98195 USA. FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD19897, HD36801, HD21410, HD21414, HD21434, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905, HD27915, HD27917]; NIH [2P01 HD30367] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD19897, HD36801, HD21410, HD21414, HD21434, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905, HD27915, and HD27917) and NIH 2P01 HD30367 NR 41 TC 8 Z9 9 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2010 VL 29 IS 4 BP 399 EP 409 DI 10.3109/10641950903214633 PG 11 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 678ZL UT WOS:000284126400006 PM 20701468 ER PT J AU Hall, KD AF Hall, Kevin D. TI Mechanisms of Metabolic Fuel Selection Modeling Human Metabolism and Body-Weight Change SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID FAT-FREE MASS; ENERGY-EXPENDITURE; MATHEMATICAL-MODEL; LOSS MAINTENANCE; CANCER CACHEXIA; OBESITY; INTERRELATIONSHIPS; PREDICTION; STARVATION; SETPOINT C1 NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Hall, KD (reprint author), NIDDKD, Lab Biol Modeling, NIH, 12A South Dr,Room 4007, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov RI Hall, Kevin/F-2383-2010 FU NIH; NIDDK FX This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 42 TC 17 Z9 17 U1 1 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JAN-FEB PY 2010 VL 29 IS 1 BP 36 EP 41 DI 10.1109/MEMB.2009.935465 PG 6 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 559IP UT WOS:000274818000008 PM 20176520 ER PT J AU Brychta, R Wohlers, E Moon, J Chen, K AF Brychta, Robert Wohlers, Erica Moon, Jon Chen, Kong TI Energy Expenditure Measurement of Human Metabolism SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID WHOLE-BODY CALORIMETER; HEART-RATE MONITOR; PHYSICAL-ACTIVITY; SYSTEM; VALIDATION; VALIDITY; BALANCE RP Brychta, R (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 6-3940, Bethesda, MD 20892 USA. EM brychtar@niddk.nih.gov NR 21 TC 10 Z9 11 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JAN-FEB PY 2010 VL 29 IS 1 BP 42 EP 47 DI 10.1109/MEMB.2009.935463 PG 6 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 559IP UT WOS:000274818000009 PM 20176521 ER PT J AU Shah, VP Younan, NH Durbha, SS King, RL AF Shah, Vijay P. Younan, Nicolas H. Durbha, Surya S. King, Roger L. TI Feature Identification via a Combined ICA-Wavelet Method for Image Information Mining SO IEEE GEOSCIENCE AND REMOTE SENSING LETTERS LA English DT Article DE Feature fusion; image information mining; independent component analysis (ICA); wavelets ID INDEPENDENT COMPONENT ANALYSIS; DATA ARCHIVES; SEGMENTATION; ALGORITHMS AB Image transformation is required for color-texture image segmentation. Various techniques are available for the transformation along the spatial and spectral axes. For instance, the HSV-wavelet technique is shown to be very effective for image information mining in remote-sensing applications. However, the HSV transformation approach uses only three spectral bands at a time. In this letter, a new feature set, obtained by combining independent component analysis and wavelet transformation for image information mining in geospatial data, is presented. Experimental results show the effectiveness of the presented method for image information mining in Earth observation data archives. C1 [Shah, Vijay P.; Younan, Nicolas H.; Durbha, Surya S.; King, Roger L.] Mississippi State Univ, Dept Elect & Comp Engn, Mississippi State, MS 39762 USA. [Shah, Vijay P.; Younan, Nicolas H.; Durbha, Surya S.; King, Roger L.] Mississippi State Univ, GeoResources Inst, Mississippi State, MS 39762 USA. RP Shah, VP (reprint author), NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. EM vijaypshah@yahoo.com; younan@ece.msstate.edu; suryad@gri.msstate.edu; rking@engr.msstate.edu RI Shah, Vijay/D-4083-2014 OI Shah, Vijay/0000-0003-3856-156X NR 25 TC 9 Z9 9 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1545-598X J9 IEEE GEOSCI REMOTE S JI IEEE Geosci. Remote Sens. Lett. PD JAN PY 2010 VL 7 IS 1 BP 18 EP 22 DI 10.1109/LGRS.2009.2020519 PG 5 WC Geochemistry & Geophysics; Engineering, Electrical & Electronic; Remote Sensing; Imaging Science & Photographic Technology SC Geochemistry & Geophysics; Engineering; Remote Sensing; Imaging Science & Photographic Technology GA 575PI UT WOS:000276079000004 ER PT J AU Jones, G Hunter, F Hancock, HA Kapoor, A Stone, MJ Wood, BJ Xie, JW Dreher, MR Frenkel, V AF Jones, Guy Hunter, Finnie Hancock, Hilary A. Kapoor, Ankur Stone, Michael J. Wood, Bradford J. Xie, Jianwu Dreher, Matthew R. Frenkel, Victor TI In Vitro Investigations Into Enhancement of tPA Bioavailability in Whole Blood Clots Using Pulsed-High Intensity Focused Ultrasound Exposures SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Acoustic radiation forces; fluorescence recovery after photobleaching (FRAP); fluorescent antibody staining; pulsed-high intensity focused ultrasound (HIFU); radio-frequency (RF); SEM; tissue plasminogen activator (tPA); whole blood clots ID TISSUE-PLASMINOGEN ACTIVATOR; THROMBOLYSIS; TRANSPORT; MODEL AB Investigations were carried out on the manner by which pulsed-high intensity focused ultrasound (HIFU) enhances the effectiveness of tissue plasminogen activator (tPA) in whole blood clots, in vitro. Scanning electronic microscope (SEM) of the surface of the clots showed that the exposures increased exposed fibrin, as well as the number of openings to more interior regions. These findings were supported by fluorescent antibody labeling of tPA in frozen sections of clots treated post-HIFU. Here, improved accumulation at the surface and penetration of the tPA into the clots were observed in those treated with HIFU. Fluorescence recovery after photobleaching was also performed, indicating that the diffusion coefficient increased 6.3-fold for fluorescently labeled dextrans, comparable in size to tPA, in the HIFU-treated clots. Improved understanding of the manner by which pulsed-HIFU exposures can improve the effectiveness of thrombolytics will help optimize the exposures for this application and potentially facilitate translation to the clinic. C1 [Frenkel, Victor] NIH, Mol Imaging Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Frenkel, V (reprint author), NIH, Mol Imaging Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM vfrenkel@cc.nih.gov FU Howard HughesMedical Institute; National Institutes of Health (NIH) Clinical Center FX The work of G. Jones and M. J. Stone was supported by the Howard HughesMedical Institute. This work was supported in part by the intramural research program of the National Institutes of Health (NIH) Clinical Center. NR 13 TC 11 Z9 11 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JAN PY 2010 VL 57 IS 1 BP 33 EP 36 DI 10.1109/TBME.2009.2028316 PG 4 WC Engineering, Biomedical SC Engineering GA 543HS UT WOS:000273565600008 PM 20064753 ER PT B AU Gaist, PA AF Gaist, Paul A. BE Gaist, PA TI Global Public Health: The Fight of Our Lives SO IGNITING THE POWER OF COMMUNITY: THE ROLE OF CBOS AND NGOS IN GLOBAL PUBLIC HEALTH LA English DT Article; Book Chapter C1 [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Gaist, Paul A.] NIH, Bethesda, MD 20892 USA. [Gaist, Paul A.] NIMH, Psychobiol Branch, Bethesda, MD 20892 USA. [Gaist, Paul A.] US Dept HHS, HIV AIDS Alcohol Drug Abuse Mental Hlth Adm, Washington, DC USA. RP Gaist, PA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-98156-7 PY 2010 BP XVII EP XXV D2 10.1007/978-0-387-98157-4 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BNC62 UT WOS:000274162300001 ER PT B AU Dharshi, AS Gaist, PA AF Dharshi, Anisha S. Gaist, Paul A. BE Gaist, PA TI Philanthropy and the Culture of Giving: Its Beginnings, Current Character, and Future Expectations SO IGNITING THE POWER OF COMMUNITY: THE ROLE OF CBOS AND NGOS IN GLOBAL PUBLIC HEALTH LA English DT Article; Book Chapter C1 [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Gaist, Paul A.] NIH, Bethesda, MD 20892 USA. [Gaist, Paul A.] NIMH, Psychobiol Branch, Bethesda, MD 20892 USA. [Gaist, Paul A.] US Dept HHS, HIV AIDS Alcohol Drug Abuse Mental Hlth Adm, Washington, DC USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-98156-7 PY 2010 BP 63 EP 76 DI 10.1007/978-0-387-98157-4_5 D2 10.1007/978-0-387-98157-4 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BNC62 UT WOS:000274162300006 ER PT B AU Gaist, PA AF Gaist, Paul A. BE Gaist, PA TI Global Public Health: Winning the Fight SO IGNITING THE POWER OF COMMUNITY: THE ROLE OF CBOS AND NGOS IN GLOBAL PUBLIC HEALTH LA English DT Article; Book Chapter C1 [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Gaist, Paul A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Gaist, Paul A.] NIH, Bethesda, MD 20892 USA. [Gaist, Paul A.] NIMH, Psychobiol Branch, Bethesda, MD 20892 USA. [Gaist, Paul A.] US Dept HHS, HIV AIDS Alcohol Drug Abuse Mental Hlth Adm, Washington, DC USA. RP Gaist, PA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-98156-7 PY 2010 BP 391 EP 394 DI 10.1007/978-0-387-98157-4_23 D2 10.1007/978-0-387-98157-4 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BNC62 UT WOS:000274162300024 ER PT J AU Gordon, IK Khanna, C AF Gordon, Ira K. Khanna, Chand TI Modeling Opportunities in Comparative Oncology for Drug Development SO ILAR JOURNAL LA English DT Article DE cancer; comparative oncology; dog; drug development; preclinical model ID COMPANION ANIMALS; CLINICAL-TRIALS; CANCER MODELS; MOUSE MODELS; IN-VITRO; HUMANS; DOGS; VIVO; MALIGNANCIES; XENOGRAFTS AB Successful development of novel cancer drugs depends on well-reasoned scientific drug discovery, rigorous preclinical development, and carefully conceived clinical trials. Failure in any of these steps contributes to poor rates of approval for new drugs to treat cancer. As technological and scientific advances have opened the door to a variety of novel approaches to cancer drug discovery and development, preclinical models that can answer questions about the activity and safety of novel therapies are increasingly necessary. The advance of a drug to clinical trials based on information from preclinical models presupposes that the models convey informative data for future use in human patients with cancer. The study of novel cancer drugs using in vitro models is highly controllable, reproducible, relatively inexpensive, and linked to high throughput. However, these models fail to reproduce many of the complex features of human cancer. Mouse models address some of these limitations but have important biological differences from human cancer. The integration of studies using pet dogs with spontaneously occurring tumors as models in the development path can answer questions not adequately addressed in conventional models and is therefore gaining attention and interest in drug development communities. The study of novel cancer drugs in dogs with naturally occurring tumors allows drug assessment in a cancer that shares many fundamental features with the human cancer condition, and thus provides an opportunity to answer questions that inform the cancer drug development path in ways not possible in more conventional models. C1 [Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Khanna, Chand] NCI, Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Gordon, Ira K.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 37 Convent Dr,Room 2144, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov FU National Cancer Institute intramural Center for Cancer Research; Comparative Oncology Trials Consortium FX We acknowledge the support of the National Cancer Institute intramural Center for Cancer Research and the active collaboration of the Comparative Oncology Trials Consortium. NR 39 TC 21 Z9 21 U1 0 U2 3 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2010 VL 51 IS 3 BP 214 EP 220 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 736LI UT WOS:000288495800004 PM 21131722 ER PT B AU Lu, HB Ross, TJ Stein, EA AF Lu, Hanbing Ross, Thomas J. Stein, Elliot A. BE Borsook, D Beccera, L Bullmore, E Hargreaves, R TI Magnetic Resonance Imaging of Pharmacological Systems SO IMAGING IN CNS DRUG DISCOVERY AND DEVELOPMENT: IMPLICATIONS FOR DISEASE AND THERAPY LA English DT Article; Book Chapter ID CEREBRAL-BLOOD-FLOW; FUNCTIONAL MRI SIGNAL; BRAIN ACTIVATION; SPONTANEOUS FLUCTUATIONS; PHARMACOKINETIC MODEL; OXYGEN-CONSUMPTION; FMRI; STIMULATION; MANGANESE; COCAINE C1 [Stein, Elliot A.] NIDA, Intramural Res Program, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. RP Stein, EA (reprint author), NIDA, Intramural Res Program, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. EM estein@intra.nida.nih.gov OI Ross, Thomas/0000-0002-7745-3572 NR 57 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0133-0 PY 2010 BP 91 EP 104 DI 10.1007/978-1-4419-0134-7_6 PG 14 WC Biotechnology & Applied Microbiology; Neurosciences; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BMI15 UT WOS:000272425300006 ER PT B AU Woicik, PA Alia-Klein, N Volkow, ND Goldstein, RZ AF Woicik, P. A. Alia-Klein, N. Volkow, N. D. Goldstein, R. Z. BE Borsook, D Beccera, L Bullmore, E Hargreaves, R TI Neuroimaging Human Drug Addiction SO IMAGING IN CNS DRUG DISCOVERY AND DEVELOPMENT: IMPLICATIONS FOR DISEASE AND THERAPY LA English DT Article; Book Chapter ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; COCAINE-SEEKING BEHAVIOR; BRAIN GLUCOSE-METABOLISM; METHAMPHETAMINE-DEPENDENT SUBJECTS; PROGRESSIVE RATIO SCHEDULE; ABSTINENT MARIJUANA USERS; ANTERIOR CINGULATE CORTEX; STRIATAL DOPAMINE RELEASE C1 [Woicik, P. A.; Alia-Klein, N.; Goldstein, R. Z.] Brookhaven Natl Lab, Ctr Translat Neuroimaging, Upton, NY 11973 USA. [Volkow, N. D.] NIDA, Bethesda, MD 20892 USA. RP Woicik, PA (reprint author), Brookhaven Natl Lab, Ctr Translat Neuroimaging, Upton, NY 11973 USA. EM pwoicik@bnl.uov; rgoldstein@bnl.gov NR 232 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0133-0 PY 2010 BP 263 EP 289 DI 10.1007/978-1-4419-0134-7_17 PG 27 WC Biotechnology & Applied Microbiology; Neurosciences; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BMI15 UT WOS:000272425300017 ER PT B AU Goldman, D Zhou, ZF AF Goldman, David Zhou, Zhifeng BE Borsook, D Beccera, L Bullmore, E Hargreaves, R TI Anxiety: Uncover Roles of Stress Related Genes by Imaging Genetics SO IMAGING IN CNS DRUG DISCOVERY AND DEVELOPMENT: IMPLICATIONS FOR DISEASE AND THERAPY LA English DT Article; Book Chapter ID CATECHOL-O-METHYLTRANSFERASE; POSITRON-EMISSION-TOMOGRAPHY; NEUROPEPTIDE-Y DISTRIBUTION; SEROTONIN TRANSPORTER; HIPPOCAMPAL VOLUME; HUMAN AMYGDALA; OPIOID NEUROTRANSMISSION; PANCREATIC-POLYPEPTIDE; ANTERIOR CINGULATE; MAJOR DEPRESSION C1 [Goldman, David] NIAAA, Neurogenet Lab, NIH, LNG, Rockville, MD 20852 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Rockville, MD 20852 USA. EM davidgoldman@mail.nih.gov NR 60 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0133-0 PY 2010 BP 291 EP 301 DI 10.1007/978-1-4419-0134-7_18 PG 11 WC Biotechnology & Applied Microbiology; Neurosciences; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Neurosciences & Neurology; Pharmacology & Pharmacy GA BMI15 UT WOS:000272425300018 ER PT S AU Chen, D Motiejunaite, R Kazlauskas, A Gudla, P Collins, J Lockett, S AF Chen, De Motiejunaite, Ruta Kazlauskas, Andrius Gudla, Prabhakar Collins, Jack Lockett, Stephen BE Farkas, DL Nicolau, DV Leif, RC TI Automatic Image Analysis method for quantification of tube formation by Endothelial cells in vitro SO IMAGING, MANIPULATION, AND ANALYSIS OF BIOMOLECULES, CELLS, AND TISSUES VIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues VII CY JAN 23-25, 2010 CL San Francisco, CA SP SPIE DE Automatic image analysis; Segmentation; In vitro endothelial cell culture; Tumor angiogenesis; Network entropy ID ANGIOGENIC FACTORS; ENHANCEMENT; ENTROPY; ASSAY; MODEL AB Early stages of tumor angiogenesis can be modeled by various in vitro cultures in which endothelial cells (ECs) form networks that are considered to mimic the vascularization of tumors in vivo. Image based quantification of EC culture model is a useful method for effective characterization of early stage in vitro vasculogenesis and the effects of pro and anti-angiogenesis reagents. We propose an image analysis method to quantify the EC tube formation in 2D cultures. The method segments images by high pass filtering in Fourier space, followed by thresholding and a skeletonization and pruning process to generate the binary skeleton image of the cell patterns in culture. Several quantities such as the network entropy (NE), the node number, total number of chords, total and average chord length were used to quantify the evolution of EC tubes. The automatic measurement of chord length was validated against manual measurement, achieving an R(2) value of 0.953, and was used to assay for tubal extension as a function of increasing VEGF concentration. Measurements of NE, node number, chord lengths were demonstrated on ECs network-like patterns in culture. C1 [Chen, De; Gudla, Prabhakar; Lockett, Stephen] Natl Canc Inst Frederick, Opt Microscopy & Anal Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Chen, D (reprint author), Natl Canc Inst Frederick, Opt Microscopy & Anal Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. EM chend2@mail.nih.gov NR 25 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 978-0-8194-7964-8 J9 PROC SPIE PY 2010 VL 7568 AR 75681G DI 10.1117/12.841290 PG 7 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BSG26 UT WOS:000284359700037 ER PT S AU Lim, MD Compton, CC AF Lim, Mark David Compton, Carolyn C. BE Farkas, DL Nicolau, DV Leif, RC TI Do you have an innovative idea that can revolutionize cancer research? Opportunities and Resources for Innovative Cancer Technologies from the National Cancer Institute SO IMAGING, MANIPULATION, AND ANALYSIS OF BIOMOLECULES, CELLS, AND TISSUES VIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues VII CY JAN 23-25, 2010 CL San Francisco, CA SP SPIE DE Innovative technologies; Translational Cancer Research; Technology Development; Funding Opportunities; NCI; NIH AB The pace of biomedical research towards reducing the onset of disease is greatly accelerated when out-of-the-box approaches are used to develop a novel technology and tool. The National Cancer Institute's program for Innovative Molecular Analysis Technologies (IMAT) continues to focus on supporting and stimulating investigator-initiated innovation to develop technologies that have the potential for revolutionizing cancer research and care. Also described in this extended abstract are other funding opportunities from the National Institutes of Health (NIH) that may be of interest to those seeking support for technology development. C1 [Lim, Mark David; Compton, Carolyn C.] NCI, Program Innovat Mol Anal Technol IMAT, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. RP Lim, MD (reprint author), NCI, Program Innovat Mol Anal Technol IMAT, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. EM limm2@mail.nih.gov NR 0 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 978-0-8194-7964-8 J9 PROC SPIE PY 2010 VL 7568 AR 75680B DI 10.1117/12.837051 PG 6 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BSG26 UT WOS:000284359700006 ER PT S AU Wiegand, G Avital, I AF Wiegand, Gordon Avital, Itzhak BE Farkas, DL Nicolau, DV Leif, RC TI CELLULAR SPECTROSCOPY AND MULTIANGLE LIGHT SCATTERING BY FLOW CYTOMETRY: OPTICAL TEST BENCH AS A DEVELOPMENTAL TOOL SO IMAGING, MANIPULATION, AND ANALYSIS OF BIOMOLECULES, CELLS, AND TISSUES VIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues VII CY JAN 23-25, 2010 CL San Francisco, CA SP SPIE DE Cellular Spectroscopy; Analytical Cytometry; Scanning Monochrometer; Multi-angle Light Scatter AB We designed and fabricated a flow cytometry work bench for the purpose of testing optical schemes utilized in two specialized flow cytometry techniques. Fluorescent spectroscopy and multi-angle scattering of laser light has potential for generating novel classes of cell population information. The acquisition of full fluorescence spectrum of dye bound to living cells may associate specific function to spectral shift. Similarly, detection of 2 discrete angles of light scatter was shown to describe internal structures of cells based on refractive and diffractive properties. We utilized a flow cytometry electro-cells based on refractive and diffractive properties. We utilized a flow cytometry electro-optical test bench to develop and describe alternate light collection schemes for these two techniques. Mouse bone marrow was chosen as the subject of analysis because it contains a consistent mix of cells that possess distinct biophysical properties. More importantly, these cells are the source of various biological systems that are targeted by environmental stress and clinical disease. Hoechst 33342 fluorescent dye binds strongly to nucleic pairs within the cell nucleus but is also retained within the outer cytoplasm were it functions as a substrate for a class of ATP driven efflux proteins associated with multi-drug resistance. Measurements of the efflux of this probe from the cell interior have been used extensively to identify and separate potential stem cells in human and mouse systems We acquired full spectrum signatures of bound and non-bound Hoechst by mounting a scanning monochrometer to a flow cytometer. Resulting spectra from bound Hoechst 33342 indicated 2 alternate emission peaks besides the primary unbound dye emission curve suggesting differential binding of potentially important precursor cells. Flow cytometry light scatter produces a well known pattern of RBC, lymphoid and granular populations from mouse bone marrow cells. We built a 2 element scatter detector to measure discrete angles of scattered light and made a correlation between refractive and diffractive sub-cellular properties. C1 [Wiegand, Gordon; Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wiegand, G (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM wiegandg@mail.nih.gov NR 12 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 978-0-8194-7964-8 J9 PROC SPIE PY 2010 VL 7568 AR 75681J DI 10.1117/12.849163 PG 9 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BSG26 UT WOS:000284359700039 ER PT S AU Grodzki, AC Berenstein, E AF Grodzki, Ana Cristina Berenstein, Elsa BE Oliver, C Jamur, MC TI Introduction to the Purification of Antibodies SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Editorial Material; Book Chapter DE Monoclonal antibodies; Polyclonal antibodies; Antibody applications; IgG; Immunoglobulins; Serum; Ascitic fluid; Hybridoma AB Antibodies are a powerful and essential tool in scientific laboratories being Used in an array of applications Rich as immuno-histochemistry, immunobloting, immunoprecipitation and enzyme-linked immunosorbent assays (ELISA). The different sources for antibodies include polyclonal antisera from immunized animals and monoclonal antibodies from cells ill culture or from ascites in animals. Both polyclonal and monoclonal antibodies have their advantages, and or disadvantages, but ill general the production of monoclonal antibodies is more time consuming and requires tissue culture facilities and skills. The use of either monoclonal or polyclonal antibodies in some of the applications may require that the antibody is in a purified form. They call be purified by a variety of methods described in the next few chapters. The availability of commercially available kits primarily designed for the purification of IgG and IgM classes of antibodies derived from all common animal species should also be mentioned. C1 [Grodzki, Ana Cristina; Berenstein, Elsa] Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Grodzki, AC (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. FU Intramural NIH HHS NR 0 TC 0 Z9 1 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 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 11 EP 13 DI 10.1007/978-1-59745-324-0_2 D2 10.1007/978-1-59745-324-0 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800002 PM 20012813 ER PT S AU Grodzki, AC Berenstein, E AF Grodzki, Ana Cristina Berenstein, Elsa BE Oliver, C Jamur, MC TI Antibody Purification: Ammonium Sulfate Fractionation or Gel Filtration SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Antibody purification; Ammonium sulfate precipitation; Fractional precipitation; Fractionation; Caprylic acid; Gel filtration; Size-exclusion chromatography; Fast Protein Liquid Chromatography; FPLC AB Antibodies call be purified by a variety of methods based oil their unique physical and chemical properties such as size, solubility, charge, hydrophobicity and binding affinity. This chapter focuses oil ammonium sulfate precipitation as a convenient first step in antibody purification in that, it allows the concentration of the starting material and the precipitation of the desired protein. The principle of ammonium sulfate precipitation lies in "salting out" proteins from the solution. The proteins are prevented to form hydrogen bonds with water and the salt facilitates their interaction with each other forming aggregates that afterward precipitate out of solution. Gel filtration or size- exclusion chromatography is also discussed in this chapter. Gel filtration is based oil the relative size of protein molecules and it is of great value to separate IgMs, exchange buffers and/or desalt solutions. The columns designed to separate the proteins are composed of porous beads and the proteins will flow through the packed column inside and around the beads, depending on its size. C1 [Grodzki, Ana Cristina; Berenstein, Elsa] Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Grodzki, AC (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. FU Intramural NIH HHS NR 8 TC 12 Z9 12 U1 9 U2 18 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 15 EP 26 DI 10.1007/978-1-59745-324-0_3 D2 10.1007/978-1-59745-324-0 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800003 PM 20012814 ER PT S AU Grodzki, AC Berenstein, E AF Grodzki, Ana Cristina Berenstein, Elsa BE Oliver, C Jamur, MC TI Antibody Purification: Ion-Exchange Chromatography SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Ion-exchange chromatography; Net surface charge; Isoelectric point; Cation exchanger; Anion exchanger; Ionic strength; DEAE column; Chromatographic matrix AB Ion exchange chromatography techniques are the focus of this chapter and they showcase the power of this method for the purification of proteins and monoclonal antibodies. The technique is powerful and can separate biomolecules that have minor differences in their net charge, e.g., two protein molecules differing by a single charged amino acid. Given the amphoteric character of proteins the pH Of the solution is important in the determination of the type of ion exchanger used. Immunoglobulins, although they can be purified by either cation or anion exchange chromatography, arc most frequently purified by anion exchange with DEAE resins. The purification of the rabbit IgG fraction from serum using a DEAE column is detailed as well as the purification of IgG from ascitic fluid using FPLC, from loading to elution of the purified and concentrated protein. C1 [Grodzki, Ana Cristina; Berenstein, Elsa] Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Grodzki, AC (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. FU Intramural NIH HHS NR 9 TC 3 Z9 3 U1 2 U2 16 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 27 EP 32 DI 10.1007/978-1-59745-324-0_4 D2 10.1007/978-1-59745-324-0 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800004 PM 20012815 ER PT S AU Grodzki, AC Berenstein, E AF Grodzki, Ana Cristina Berenstein, Elsa BE Oliver, C Jamur, MC TI Antibody Purification: Affinity Chromatography - Protein A and Protein G Sepharose SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Affinity chromatography; Affinity matrices; Antigen-specific antibodies; Hapten-specific antibodies; Specie-specific antibodies; Cross-reacting immunoglobulin; Sepharose; Affigel; IgM; IgA; Mannan binding protein; Jacalin; Protein A; Protein G; Protein L AB Affinity chromatography relies on the reversible interaction between a protein and a specific ligand immobilized in a chromatographic matrix. The sample is applied under conditions that favor specific binding to the ligand as the result Of electrostatic and hydrophobic interactions, van der Waals' forces and/or hydrogen bonding. After washing away the unbound material the bound protein is recovered by changing the buffer conditions to those that favor desorption. The technique has been used not only to isolate antigen-specific antibodies but also to remove specific contaminants from biological samples. Methods are described for the purification of immunoglobulins, namely IgG, IgG fragments and subclasses, using the high affinity of protein A and protein G Coupled to agarose. In the Subheading 3 there are also protocols for affinity purification using a specific ligand Coupled to commercial matrices like CNBr- Sepharose 4-B and Affigel. C1 [Grodzki, Ana Cristina; Berenstein, Elsa] Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Grodzki, AC (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. FU Intramural NIH HHS NR 7 TC 22 Z9 27 U1 1 U2 12 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 33 EP 41 DI 10.1007/978-1-59745-324-0_5 D2 10.1007/978-1-59745-324-0 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800005 PM 20012816 ER PT S AU Krenacs, L Krenacs, T Stelkovics, E Raffeld, M AF Krenacs, Laszlo Krenacs, Tibor Stelkovics, Eva Raffeld, Mark BE Oliver, C Jamur, MC TI Heat-Induced Antigen Retrieval for Immunohistochemical Reactions in Routinely Processed Paraffin Sections SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Heat-induced epitope retrieval; Archived tissues; Restoring epitope conformation; Paraffin sections; Time and temperature control; Microwave; Pressure cooker; Citrate buffer pH 6.0; Tris buffer pH 8.0; Tris-EDTA buffer pH 9.0 ID EMBEDDED TISSUE-SECTIONS; EPITOPE RETRIEVAL; FORMALIN; PRETREATMENT; ENHANCEMENT; ANTIBODIES; DIGESTION; CELLS AB The development of heat-induced antigen (epitope) retrieval (HIER) technologies has led to dramatic improvements in Our ability to detect antigens in formalin fixed, archival tissues. Paradoxically,wet heat treatment at temperatures greater than 95 degrees C in appropriate buffer solutions call reconstitute the antigenicity of many proteins that have been rendered nonreactive during the fixation and paraffin embedding process, which heretofore could only be identified in fresh or frozen tissues. The reason for this effect is unclear, but it has been suggested that the vigorous heat treatment partially reverses or disrupts the aldehyde cross-links Occurring in proteins during formalin fixation and restores the original conformation of antigenic epitopes. The great success of antigen/epitope retrieval technologies further emphasizes the importance of preanalytical steps in immunohistochemistry. Over the past several years, since this technology was first reported, there have been numerous modifications to the original formulation. It is the purpose of this chapter to discuss the critical issues required for optimal HIER and to provide guidelines for the use of popular HIER buffers and heating devices used for routine immunohistochemical detection. C1 [Krenacs, Laszlo; Stelkovics, Eva] Bay Zoltan Fdn Appl Res, Lab Tumor Pathol & Mol Diagnost, Szeged, Hungary. [Krenacs, Tibor] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, Budapest, Hungary. [Raffeld, Mark] NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. RP Krenacs, L (reprint author), Bay Zoltan Fdn Appl Res, Lab Tumor Pathol & Mol Diagnost, Szeged, Hungary. NR 23 TC 7 Z9 9 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 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 103 EP 119 DI 10.1007/978-1-59745-324-0_14 D2 10.1007/978-1-59745-324-0 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800014 PM 20012825 ER PT S AU Swaim, WD AF Swaim, William D. BE Oliver, C Jamur, MC TI Overview of Confocal Microscopy SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Confocal microscopy; Sample preparation; DAPI; FRAP; FRET; 2-Photon imaging ID RESONANCE ENERGY-TRANSFER; LIVING CELLS; FLUORESCENCE RECOVERY; LATERAL DIFFUSION; PROTEINS; DYNAMICS; FRET; MOBILITY; SINGLE; TOOLS AB Born out of the need to overcome an imaging problem in the 1950s, confocal microscopes today allow researchers to go beyond simple imaging and ask biochemical questions. This chapter provides background information on the development of modern confocal microscopes, their uses and applications. Sample preparation and observation arc also discussed. Information is also provided about more advanced applications such as FRAP, FRET and 2-photon imaging. The requirements for setting Lip a confocal laboratory and the instrumentation needs arc also discussed. C1 Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. RP Swaim, WD (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. NR 30 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 187 EP 201 DI 10.1007/978-1-59745-324-0_21 D2 10.1007/978-1-59745-324-0 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800021 PM 20012832 ER PT S AU Raffeld, M Jaffe, ES AF Raffeld, Mark Jaffe, Elaine S. BE Oliver, C Jamur, MC TI Avidin-Biotin Labeling of Cellular Antigens in Cryostat-Sectioned Tissue SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Frozen section immunohistochemistry; Avidin-biotin complex (ABC); Diaminobenzedine (DAB); Monoclonal antibodies; Polyclonal antibodies ID UNLABELED ANTIBODY; ABC AB Advances in immunohistochemical technologies have greatly improved the ability to Visualize antigens in for malin-fixed paraffin-embedded tissues. Nonetheless, there arc occasions in which there may be no alternative to the use of cryostat-sectioned frozen tissues. While the basic chemistries and techniques used in staining cryostat-sectioned tissues arc identical to those employed for staining paraffin-embedded sections, there are some unique issues to consider with frozen sections. Achieving excellent results requires the use of properly prepared and stored frozen tissue blocks embedded in ail appropriate mounting compound, properly prepared and mounted cryostat-prepared sections, blocking of endogenous biotin and peroxidases that might interfere with interpretation of specific staining, and a mild postsectioning fixation step. This chapter describes a general frozen-section immmunostaining procedure that provides guidelines for handling these special considerations. C1 [Raffeld, Mark; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Raffeld, M (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 7 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 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 271 EP 279 DI 10.1007/978-1-59745-324-0_27 D2 10.1007/978-1-59745-324-0 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800027 PM 20012838 ER PT S AU Krenacs, T Krenacs, L Raffeld, M AF Krenacs, Tibor Krenacs, Laszlo Raffeld, Mark BE Oliver, C Jamur, MC TI Multiple Antigen Immunostaining Procedures SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Multiple antigen immunostaining; Immunoenzymatic methods; Immunofluorescence; Noncross-reacting antibodies; Simultaneous antigen detection ID PROCESSED PARAFFIN SECTIONS; MONOCLONAL-ANTIBODIES; ALKALINE-PHOSPHATASE; INDIRECT IMMUNOFLUORESCENCE; SIMULTANEOUS LOCALIZATION; POLYCLONAL ANTIBODIES; PRIMARY ANTISERA; LYMPHOID-TISSUE; STAINING METHOD; SILVER AB Detection Of Multiple antigens in the same tissue section can be done by combining a range of immunohisto/cytochemical techniques based either on light microscopic chromogenic precipitates or fluorochronic labeling. Light microscopic techniques preferred for this purpose use combinations of immunogold silver staining (black precipitate), immunoperoxidase, immunoalkaline phosphatase and immunogalactosidase methods using chromogens of different colors. Fluorochrome labels favored for these combinations include AMCA (blue), FITc (green), rhodamine (orange-red) and Cy5 (far red), their matching synthetic members from the Alexa series, or quantum dots. Antibodies directly labeled or those from noncross-reacting animal species (e.g., mouse, rabbit, goat, guinea pig etc.) can be applied simultaneously. When the antigens of interest arc in separate cells or cell compartments (e.g., in cell membrane, cytoplasm or nucleus), and only cross-reacting antibodies arc available, there have also been ways of avoiding unwanted cross-talk. These include the exploitation of the shielding effect of chromogens; inactivation of immumo-sequences of the first staining by using either acidic elution, formaldehyde fixation or microwave heating; combining Unlabeled and hapten-labeled antibodies; or using labeled monovalent F(ab) secondary antibodies. In this chapter we briefly discuss the principle of multiple antigen immunolabeling and provide useful protocols for its performance. C1 [Krenacs, Tibor] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, Budapest, Hungary. [Krenacs, Laszlo] Bay Zoltan Fdn Appl Res, Lab Tumor Pathol & Mol Diagnost, Szeged, Hungary. [Raffeld, Mark] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Krenacs, T (reprint author), Semmelweis Univ, Dept Pathol & Expt Canc Res 1, Budapest, Hungary. NR 40 TC 7 Z9 8 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 281 EP 300 DI 10.1007/978-1-59745-324-0_28 D2 10.1007/978-1-59745-324-0 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800028 PM 20012839 ER PT S AU Fetsch, PA Abati, A AF Fetsch, Patricia A. Abati, Andrea BE Oliver, C Jamur, MC TI The Clinical Immunohistochemistry Laboratory: Regulations and Troubleshooting Guidelines SO IMMUNOCYTOCHEMICAL METHODS AND PROTOCOLS, THIRD EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE CLIA-88; Immunohistochemistry regulations; College of American Pathologists AB The Clinical Laboratory Improvement Amendments (CLIA) set standards designed to improve the quality of all laboratory testing. In the first portion of this chapter, we discuss the CLIA requirements that apply to most Immunohistochemistry laboratories, and explain topics such as certification, test complexity, patient test management, proficiency testing, personnel, quality control, quality assurance, and compliance. The second portion of this chapter addresses the most common problems encountered in immunohistochemical procedures and the appropriate solutions to correct them. C1 [Fetsch, Patricia A.; Abati, Andrea] NCI, Pathol Lab, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. RP Fetsch, PA (reprint author), NCI, Pathol Lab, Cytopathol Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 3 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-463-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 588 BP 399 EP 412 DI 10.1007/978-1-59745-324-0_43 D2 10.1007/978-1-59745-324-0 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BND72 UT WOS:000274239800043 PM 20012854 ER PT J AU Colbert, RA DeLay, ML Klenk, EI Layh-Schmitt, G AF Colbert, Robert A. DeLay, Monica L. Klenk, Erin I. Layh-Schmitt, Gerlinde TI From HLA-B27 to spondyloarthritis: a journey through the ER SO IMMUNOLOGICAL REVIEWS LA English DT Review DE antigen presentation; processing; monocytes; macrophages; ankylosing spondylitis; major histocompatibility complex; Toll-like receptors; pattern recognition receptors; unfolded protein response ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; CLASS-I MOLECULES; SPONTANEOUS INFLAMMATORY DISEASE; ANKYLOSING-SPONDYLITIS; TRANSGENIC RATS; HEAVY-CHAINS; CELL-DEATH; HLA-B-ASTERISK-2709 SUBTYPE; HLA-B27-TRANSGENIC RATS AB Almost four decades of research into the role of human leukocyte antigen-B27 (HLA-B27) in susceptibility to spondyloarthritis has yet to yield a convincing answer. New results from an HLA-B27 transgenic rat model now demonstrate quite convincingly that CD8+ T cells are not required for the inflammatory phenotype. Discoveries that the HLA-B27 heavy chain has a tendency to misfold during the assembly of class I complexes in the endoplasmic reticulum (ER) and to form aberrant disulfide-linked dimers after transport to the cell surface have forced the generation of new ideas about its role in disease pathogenesis. In transgenic rats, HLA-B27 misfolding generates ER stress and leads to activation of the unfolded protein response, which dramatically enhances the production of interleukin-23 (IL-23) in response to pattern recognition receptor agonists. These findings have led to the discovery of striking T-helper 17 cell activation and expansion in this animal model, consistent with results emerging from humans with spondyloarthritis and the discovery of IL23R as an additional susceptibility gene for ankylosing spondylitis. Together, these results suggest a novel link between HLA-B27 and the T-helper 17 axis through the consequences of protein misfolding and open new avenues of investigation as well as identifying new targets for therapeutic intervention in this group of diseases. C1 [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA. [DeLay, Monica L.; Klenk, Erin I.; Layh-Schmitt, Gerlinde] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. RP Colbert, RA (reprint author), NIAMS, NIH, Bldg 10 CRC,Rm 1-5142 10 Ctr Dr,MSC 1102, Bethesda, MD 20892 USA. EM colbertr@mail.nih.gov FU Pfizer; National Institutes of Health [AR46177, AR48372]; Arthritis Foundation FX This work was supported by a Pfizer Scholar Award, and grants from the National Institutes of Health (AR46177 and AR48372) and the Arthritis Foundation (Biomedical Science Grant) to R. A. C. The authors thank members of the Colbert lab who, over the years, have contributed to our understanding of the immunobiology of HLA-B27, including David E. Adams, Shuzhen Bai, Huyla Bukulmez, Nandita Dangoria, Thomas Griffin, Daniel Kingsbury, Gerlinde Layh-Schmitt, John Mear, Rajashree Mohapatra, Kathy Schreiber, Dawn Sowders, Judith Smith, and Matthew Turner. We also thank Joel Taurog for contributing HLA-B27/h beta 2m transgenic rats used for the experiment shown in Fig. 7. NR 134 TC 71 Z9 75 U1 1 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2010 VL 233 BP 181 EP 202 PG 22 WC Immunology SC Immunology GA 536TW UT WOS:000273067700012 PM 20193000 ER PT S AU Tolar, P Pierce, SK AF Tolar, Pavel Pierce, Susan K. BE Saito, T Batista, FD TI A Conformation-Induced Oligomerization Model for B cell Receptor Microclustering and Signaling SO IMMUNOLOGICAL SYNAPSE SE Current Topics in Microbiology and Immunology LA English DT Review; Book Chapter ID MEDIATED IMMUNE PRECIPITATION; RESONANCE ENERGY-TRANSFER; ANTIGEN-RECEPTOR; SYNAPSE FORMATION; LYMPH-NODE; SUBCAPSULAR SINUS; LIVING CELLS; FC; ACTIVATION; ADHESION AB The B cell receptor (BCR) generates both antigen-independent and dependent intracellular signals that are essential for B cell development and antibody responses against pathogens. However, the molecular mechanisms underlying the initiation of BCR signaling are not understood completely yet. The advent of new imaging technologies is allowing the earliest events in B cell signaling to be viewed both in vivo in lymphoid tissues and in vitro in living cells, in real-time, down to the single molecule level. Here we review recent progress in the use of these technologies to decipher the earliest events that follow B cell antigen recognition. Based on recent data using these techniques, we propose a model for the initiation of BCR signaling in which the binding of antigen induces a conformational change in the BCR's extracellular domains leading to BCR oligomerization and signaling. We conclude that testing this model will require an in-depth understanding of the unique structural and organizational features of the BCR in the plasma membrane of living B cells in the presence and absence of antigen. C1 [Tolar, Pavel; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM spierce@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 51 TC 14 Z9 15 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-642-03857-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2010 VL 340 BP 155 EP 169 DI 10.1007/978-3-642-03858-7_8 D2 10.1007/978-3-642-03858-7 PG 15 WC Immunology; Microbiology SC Immunology; Microbiology GA BNG39 UT WOS:000274501800008 PM 19960313 ER PT J AU Shanker, A Buferne, M Schmitt-Verhulst, AM AF Shanker, Anil Buferne, Michel Schmitt-Verhulst, Anne-Marie TI Cooperative action of CD8 T lymphocytes and natural killer cells controls tumour growth under conditions of restricted T-cell receptor diversity SO IMMUNOLOGY LA English DT Article DE anti-tumour cytotoxicity; Ld; P1A-specific T-cell receptor transgenic mice; natural killer cells; proliferation; T-cell activation; tolerance ID LINEAGE COMMITMENT; REJECTION ANTIGEN; NK CELLS; MEMORY; NAIVE; DIFFERENTIATION; P815; GENE; IMMUNITY; PEPTIDE AB P>In mice expressing a transgenic T-cell receptor (TCR; TCRP1A) of DBA/2 origin with reactivity towards a cancer-germline antigen P1A, the number of TCRP1A CD8+ T cells in lymphoid organs is lower in DBA/2 than in B10.D2 or B10.D2(x DBA/2)F(1) mice. This reduction results from haemopoietic cell autonomous differences in the differentiation of the major histocompatibility complex class I-restricted TCRP1A thymocytes controlled by DBA/2 versus B10.D2-encoded genes. We report here that the lower number of TCRP1A CD8+ T cells in DBA/2 mice correlated with their poor resistance to P1A-expressing mastocytoma solid tumours. Functional potency of CD8+ cytolytic T lymphocytes (CTL) from the above strains was not compromised, but their number after expansion appeared to be influenced by their genetic background. Intriguingly, non-transgenic DBA/2 mice resisted P1A+ tumours more efficiently despite poor representation of P1A-specific CTL. This was partly the result of their more heterogeneous TCR repertoire, including reactivity to non-P1A tumour antigens because mice that had rejected a P1A+ tumour became resistant to a P1A- variant of the tumour. Such 'cross-resistance' did not develop in the TCRP1A transgenic mice. Nonetheless, reconstitution of RAG boolean OR/boolean OR mice with TCRP1A CD8+ T cells, with or without CD4+ T cells, or exclusive representation of TCRP1A CD8+ T cells in RAG boolean OR/boolean OR TCRP1A transgenic mice efficiently resisted the growth of P1A-expressing tumours. Natural killer cells present at a higher number in RAG boolean OR/boolean OR mice also contributed to tumour resistance, in part through an NKG2D-dependent mechanism. Hence, in the absence of a polyclonal T-cell repertoire, precursor frequencies of natural killer cells and tumour-specific CTL affect tumour resistance. C1 [Shanker, Anil; Buferne, Michel; Schmitt-Verhulst, Anne-Marie] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, Marseille, France. [Shanker, Anil; Buferne, Michel; Schmitt-Verhulst, Anne-Marie] INSERM, U631, F-13258 Marseille, France. [Shanker, Anil; Buferne, Michel; Schmitt-Verhulst, Anne-Marie] CNRS, UMR6102, Marseille, France. RP Shanker, A (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, SAIC Frederick Inc, Bldg 560,Room 31-27, Frederick, MD 21702 USA. EM shankera@mail.nih.gov; verhulst@ciml.univ-mrs.fr OI Shanker, Anil/0000-0001-6372-3669 FU Institut National de la Sante et de la Recherche Medicale; Centre National de la Recherche Scientifique; Association pour la Recherche sur le Cancer; Institut National du Cancer; European Communities [QLG1-1999-00622]; International Union Against Cancer FX This work was supported by institutional funding from Institut National de la Sante et de la Recherche Medicale and Centre National de la Recherche Scientifique, and by grants from Association pour la Recherche sur le Cancer, Institut National du Cancer and the European Communities (QLG1-1999-00622). A.S. was supported in part by an ICRETT fellowship from the International Union Against Cancer. We thank L. Leserman, B. Van den Eynde, G. Verdeil, N. Auphan-Anezin, E.-M. Inderberg-Suso and H.A. Young for assistance or intellectual feedback on the manuscript. NR 36 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JAN PY 2010 VL 129 IS 1 BP 41 EP 54 DI 10.1111/j.1365-2567.2009.03150.x PG 14 WC Immunology SC Immunology GA 529RJ UT WOS:000272534600005 PM 20050329 ER PT J AU Moir, S Fauci, AS AF Moir, Susan Fauci, Anthony S. TI HIV immune dysregulation Nef, macrophages and B cells: a highway for evasion SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Editorial Material ID INFECTION; PATHOGENESIS; ACTIVATION; RETROVIRUS; LESSONS; DISEASE; AIDS C1 [Moir, Susan; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 6A02, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov FU Intramural NIH HHS [ZIA AI000825-12] NR 21 TC 12 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JAN PY 2010 VL 88 IS 1 BP 1 EP 2 DI 10.1038/icb.2009.82 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 545GT UT WOS:000273721200001 PM 19859083 ER PT S AU De Groot, AS Cohen, T Ardito, M Moise, L Martin, B Berzofsky, JA AF De Groot, Anne S. Cohen, Tobias Ardito, Matthew Moise, Lenny Martin, Bill Berzofsky, Jay A. BE Kabelitz, D Kaufmann, SHE TI Use of Bioinformatics to Predict MHC Ligands and T-Cell Epitopes: Application to Epitope-Driven Vaccine Design SO IMMUNOLOGY OF INFECTION, THIRD EDITION SE Methods in Microbiology LA English DT Review; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLASS-I MOLECULES; HEPATITIS-C VIRUS; HUMAN CARCINOEMBRYONIC ANTIGEN; HLA-A2 TRANSGENIC MICE; MYCOBACTERIUM-TUBERCULOSIS; PEPTIDE-BINDING; DNA VACCINES; COSTIMULATORY MOLECULES; CTL EPITOPE C1 [De Groot, Anne S.; Cohen, Tobias; Ardito, Matthew; Moise, Lenny; Martin, Bill] EpiVax Inc, Providence, RI USA. [De Groot, Anne S.; Moise, Lenny] Univ Rhode Isl, Inst Immunol & Informat, Providence, RI 02908 USA. [Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP De Groot, AS (reprint author), EpiVax Inc, Providence, RI USA. OI De Groot, Annie/0000-0001-5911-1459 NR 149 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0580-9517 BN 978-0-12-374842-3 J9 METHOD MICROBIOL JI Methods Microbiol. PY 2010 VL 37 BP 35 EP 66 DI 10.1016/S0580-9517(10)37003-6 PG 32 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA BSD78 UT WOS:000284236400003 ER PT S AU Germolec, DR Frawley, RP Evans, E AF Germolec, Dori R. Frawley, Rachel P. Evans, Ellen BE Dietert, RR TI Markers of Inflammation SO IMMUNOTOXICITY TESTING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Acute phase proteins; Basophil; Chemokine; Clinical pathology; Complement; Cytokine; Eosinophil; Hematology; Inflammation; Lymphocyte; Macrophage; Monocyte; Neutrophil; Platelet ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; CHEMOKINES; MICE; BIOMARKERS; FIBRINOGEN; ATHEROSCLEROSIS; COMPLEMENT; RESPONSES; INNATE AB Inflammation is a complex and necessary component of an organism's response to biological, chemical or physical stimuli. In the acute phase, cells of the immune system migrate to the site of injury in a carefully orchestrated sequence of events that is mediated by cytokines and acute phase proteins. Depending upon the degree of injury, this acute phase may be sufficient to resolve the damage and initiate healing. persistent inflammation as a result of prolonged exposure to stimulus or an inappropriate reaction to self molecules can lead to the chronic phase, in which tissue damage and fibrosis can occur: Chronic inflammation is reported to contribute to numerous diseases including allergy, arthritis, asthma, atherosclerosis, autoimmune diseases, diabetes, and cancer, and to conditions of aging. Hematology and clinical chemistry data front standard toxicology studies can provide an initial indication of the presence and sometimes location of inflammation in the absence of specific data on the immune tissues. These data play suggest more specific immune function assays are necessary to determine the existence or mechanism(s) of immunomodulation. Although changes in hematology dynamics, acute phase proteins, complement factors and cytokines are common to virtually all inflammatory conditions and can be measured by a variety of techniques, individual biomarkers have yet to be strongly associated with specific pathologic events. The specific profile in a given inflammatory condition is dependent upon species, mechanisms, severity, chronicity, and capacity of the immune system to respond and adapt. C1 [Germolec, Dori R.; Frawley, Rachel P.] NIEHS, Toxicol Branch, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Evans, Ellen] Schering Plough Res Inst, Lafayette, NJ USA. RP Germolec, DR (reprint author), NIEHS, Toxicol Branch, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. OI Frawley, Rachel/0000-0001-8490-8240 FU Intramural NIH HHS NR 52 TC 14 Z9 14 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 978-1-60761-400-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 598 BP 53 EP 73 DI 10.1007/978-1-60761-401-2_5 D2 10.1007/978-1-60761-401-2 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNN50 UT WOS:000275067300005 PM 19967506 ER PT S AU Elmore, SA AF Elmore, Susan A. BE Dietert, RR TI Enhanced Histopathology Evaluation of Lymphoid Organs SO IMMUNOTOXICITY TESTING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Enhanced histopathology; Thymus; Spleen; Lymph nodes; MALT; Bone marrow ID IMMUNE-SYSTEM; PATHOLOGY CONSIDERATIONS; BONE-MARROW; HISTOLOGY; IMMUNOTOXICITY; THYMUS; RAT; GUIDELINE; SPLEEN; TISSUE AB Enhanced histopathology is a tool that the pathologist can use as a screening test to identify immunomodulatory compounds. This assessment is based on the assumption that chemically induced alterations may result in qualitative or quantitative changes in the histology of the lymphoid organs. It involves the histological evaluation of various lymphoid organs and their respective tissue compartments to identify specific cellular and architectural changes. Although this methodology cannot directly measure immune function, it does have the potential to determine whether or not a specific chemical causes suppression or enhancement of the immune system. As with all screening tests, evaluation of, and comparison with, control tissues are crucial in order to establish the range of normal tissue changes for a particular group of animals. Laboratory animals include species other than rat and mouse; therefore, recognition of species differences in the structure and function of the immune system should be noted as hell as identification of which differences are biologically relevant for the endpoint being considered. Consideration should also be given to the nutritional status, antigen load, age, spontaneous lesions, steroid hormone status, and stress for each strain and group of animals. General guidelines for the examination of each of the lymphoid organs are provided in this chapter. C1 NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. RP Elmore, SA (reprint author), NIEHS, Cellular & Mol Pathol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-400-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2010 VL 598 BP 323 EP 339 DI 10.1007/978-1-60761-401-2_22 D2 10.1007/978-1-60761-401-2 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNN50 UT WOS:000275067300022 PM 19967523 ER PT B AU Swarz, J Ousley, A Johnson, L Kwon, H Magro, A AF Swarz, Jeffrey Ousley, Anita Johnson, Lenora Kwon, Harry Magro, Adriane BE Carrasquero, JV Holmqvist, M McEachron, D Tremante, A Welsch, F TI CancerSPACE: An Interactive E-learning Tool for Healthcare Professionals SO IMSCI 10: 4TH INTERNATIONAL MULTI-CONFERENCE ON SOCIETY, CYBERNETICS AND INFORMATICS, VOL I LA English DT Proceedings Paper CT 4th International Multi-Conference on Society, Cybernetics and Informatics CY JUN 29-JUL 02, 2010 CL Orlando, FL SP Int Inst Informat & Syst DE Cancer; Screening Rates; Disparities; Community Health Center; Provider Education; Games; National Cancer Institute ID SIMULATION; EDUCATION AB This paper describes the development of CancerSPACE (Simulating Practice And Collaborative Education), a simulation-based, online e-learning tool for healthcare providers that aims to increase cancer screening rates for underserved and minority populations that bear a disproportional share of the cancer burden. It presents insight into the purpose of developing this type of educational tool as well as the reasoning and theories behind development. This paper also discusses different obstacles that were faced throughout development and how they were subsequently approached. The goal is to guide others in development of simulated e-learning tools which are focused on improving chronic and preventive care. Once the final version is completed, CancerSPACE will be evaluated to help expand the evidence-base available for guiding future efforts. C1 [Swarz, Jeffrey; Ousley, Anita; Johnson, Lenora; Kwon, Harry; Magro, Adriane] NCI, Off Commun & Educ, 6116 Execut Blvd, Rockville, MD 20852 USA. RP Swarz, J (reprint author), NCI, Off Commun & Educ, 6116 Execut Blvd, Rockville, MD 20852 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU INT INST INFORMATICS & SYSTEMICS PI ORLANDO PA 14269 LORD BARCLAY DR, ORLANDO, FL 32837 USA BN 978-1-936338-05-4 PY 2010 BP 172 EP 177 PG 6 WC Computer Science, Cybernetics; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BG7II UT WOS:000391343500035 ER PT J AU Minata, M Harada, KH Karrman, A Hitomi, T Hirosawa, M Murata, M Gonzalez, FJ Koizumi, A AF Minata, Mutsuko Harada, Kouji H. Karrman, Anna Hitomi, Toshiaki Hirosawa, Michi Murata, Mariko Gonzalez, Frank J. Koizumi, Akio TI Role of Peroxisome Proliferator-activated Receptor-alpha in Hepatobiliary Injury Induced by Ammonium Perfluorooctanoate in Mouse Liver SO INDUSTRIAL HEALTH LA English DT Article DE Peroxisome proliferator-activated receptor-alpha; Perfluorooctanoic acid; Hepatobiliary injury; Bile acid transporter; Histopathology ID PPAR-ALPHA; NUCLEAR RECEPTORS; BILE-ACID; PERFLUORODECANOIC-ACID; EXPORT PUMP; WILD-TYPE; MICE; TRANSPORTERS; EXPRESSION; HEPATOCARCINOGENESIS AB Peroxisome proliferator-activated receptor-alpha (PPAR alpha) has been suggested to protect against chemically induced hepatobiliary injuries in rodents. This function could mask the potential toxicities of perfluorooctanoic acid (PFOA) that is an emerging environmental contaminant and a weak ligand of PPAR alpha. However its function has not been clarified. In this study, PFOA was found to elicit hepatocyte and bile duct injuries in Ppar alpha-null mice after 4 wk treatment with PFOA ammonium salt (0, 12.5, 25, 50 mu mol/kg/d, gavage). In wild-type mice, PFOA caused major hepatocellular damage dose-dependently and minor cholangiopathy observed only at 25 and 50 mu mol/kg. In treated Ppar alpha-null mice, PFOA produced marked fat accumulation, severe cholangiopathy, hepatocellular damage and apoptotic cells especially in bile ducts. Oxidative stress was also increased 4-fold at 50 mu mol/kg and TNF-alpha mRNA was upregulated more than 3-fold at 25 mu mol/kg in Ppar alpha-null mice. Biliary bile acid/phospholipid ratios were higher in Ppar alpha-null mice than in wild-type mice. Results from these studies suggest that PPAR alpha is protective against PFOA and have a critical role in drug induced hepatobiliary injury. C1 [Minata, Mutsuko; Harada, Kouji H.; Hitomi, Toshiaki; Hirosawa, Michi; Koizumi, Akio] Kyoto Univ, Grad Sch Med, Dept Hlth & Environm Sci, Kyoto 6068501, Japan. [Karrman, Anna] Univ Orebro, MTM Res Ctr, S-70182 Orebro, Sweden. [Murata, Mariko] Mie Univ, Grad Sch Med, Dept Environm & Mol Med, Tsu, Mie 5148507, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Koizumi, A (reprint author), Kyoto Univ, Grad Sch Med, Dept Hlth & Environm Sci, Kyoto 6068501, Japan. EM koizumi@pbh.med.kyoto-u.ac.jp FU Japan Society for the Promotion of Science [19890107, 20590597, 20590600, JSPS PE7509] FX This work was supported by Grants-in-Aid from the Japan Society for the Promotion of Science (grant number 19890107, 20590597, 20590600 and JSPS PE7509). NR 34 TC 16 Z9 17 U1 2 U2 6 PU NATL INST OCCUPATIONAL SAFETY & HEALTH, JAPAN PI KAWASAKI KANAGAWA PA 21-1 NAGAO 6-CHOME TAMA-KU, KAWASAKI KANAGAWA, 214, JAPAN SN 0019-8366 J9 IND HEALTH JI Ind. Health PD JAN PY 2010 VL 48 IS 1 BP 96 EP 107 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 550HQ UT WOS:000274119300013 PM 20160413 ER PT J AU Child, R Wehrly, TD Rockx-Brouwer, D Dorward, DW Celli, J AF Child, Robert Wehrly, Tara D. Rockx-Brouwer, Dedeke Dorward, David W. Celli, Jean TI Acid Phosphatases Do Not Contribute to the Pathogenesis of Type A Francisella tularensis SO INFECTION AND IMMUNITY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; INTRAMACROPHAGE SURVIVAL; LEGIONELLA-PNEUMOPHILA; PHAGOSOMAL ESCAPE; VIRULENCE FACTORS; HUMAN MACROPHAGES; SECRETION SYSTEM; NOVICIDA; IDENTIFICATION; ACPA AB The intracellular pathogen Francisella tularensis is the causative agent of tularemia, a zoonosis that can affect humans with potentially lethal consequences. Essential to Francisella virulence is its ability to survive and proliferate within phagocytes through phagosomal escape and cytosolic replication. Francisella spp. encode a variety of acid phosphatases, whose roles in phagosomal escape and virulence have been documented yet remain controversial. Here we have examined in the highly virulent (type A) F. tularensis strain Schu S4 the pathogenic roles of three distinct acid phosphatases, AcpA, AcpB, and AcpC, that are most conserved between Francisella subspecies. Neither the deletion of acpA nor the combination of acpA, acpB, and acpC deletions affected the phagosomal escape or cytosolic growth of Schu S4 in murine and human macrophages, despite decreases in acid phosphatase activities by as much as 95%. Furthermore, none of these mutants were affected in their ability to cause lethality in mice upon intranasal inoculation. Hence, the acid phosphatases AcpA, AcpB, and AcpC do not contribute to intracellular pathogenesis and do not play a major role in the virulence of type A Francisella strains. C1 [Child, Robert; Wehrly, Tara D.; Rockx-Brouwer, Dedeke; Celli, Jean] NIAID, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Dorward, David W.] NIAID, Electron Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Celli, J (reprint author), NIAID, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jcelli@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 47 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2010 VL 78 IS 1 BP 59 EP 67 DI 10.1128/IAI.00965-09 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 535QC UT WOS:000272984300005 PM 19858304 ER PT J AU Burtnick, MN DeShazer, D Nair, V Gherardini, FC Brett, PJ AF Burtnick, Mary N. DeShazer, David Nair, Vinod Gherardini, Frank C. Brett, Paul J. TI Burkholderia mallei Cluster 1 Type VI Secretion Mutants Exhibit Growth and Actin Polymerization Defects in RAW 264.7 Murine Macrophages SO INFECTION AND IMMUNITY LA English DT Article ID FRANCISELLA PATHOGENICITY ISLAND; VIRULENCE DETERMINANT; SALMONELLA-ENTERICA; RESPONSE REGULATOR; EDWARDSIELLA-TARDA; EUKARYOTIC CELLS; IN-VIVO; SYSTEM; PSEUDOMALLEI; PROTEIN AB Burkholderia mallei is a facultative intracellular pathogen that causes severe disease in animals and humans. Recent studies have shown that the cluster 1 type VI secretion system (T6SS-1) expressed by this organism is essential for survival in a hamster model of glanders. To better understand the role of T6SS-1 in the pathogenesis of disease, studies were initiated to examine the interactions of B. mallei tssE mutants with RAW 264.7 murine macrophages. Results obtained by utilizing modified gentamicin protection assays indicated that although the tssE mutants were able to survive within RAW 264.7 cells, significant growth defects were observed in comparison to controls. In addition, analysis of infected monolayers by differential interference contrast and fluorescence microscopy demonstrated that the tssE mutants lacked the ability to induce multinucleated giant cell formation. Via the use of fluorescence microscopy, tssE mutants were shown to undergo escape from lysosome-associated membrane protein 1-positive vacuoles. Curiously, however, following entry into the cytosol, the mutants exhibited actin polymerization defects resulting in inefficient intra-and intercellular spread characteristics. Importantly, all mutant phenotypes observed in this study could be restored by complementation. Based upon these findings, it appears that T6SS-1 plays a critical role in growth and actin-based motility following uptake of B. mallei by RAW 264.7 cells. C1 [Burtnick, Mary N.; Brett, Paul J.] Univ S Alabama, Dept Microbiol & Immunol, Mobile, AL 36688 USA. [DeShazer, David] USA, Bacteriol Div, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Nair, Vinod] NIAID, Res Technol Sect, RTB, NIH, Hamilton, MT 59840 USA. [Gherardini, Frank C.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Brett, PJ (reprint author), Univ S Alabama, Dept Microbiol & Immunol, 307 Univ Blvd, Mobile, AL 36688 USA. EM pbrett@jaguar1.usouthal.edu FU NIH; National Institute of Allergy and Infectious Diseases FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 66 TC 50 Z9 50 U1 2 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2010 VL 78 IS 1 BP 88 EP 99 DI 10.1128/IAI.00985-09 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 535QC UT WOS:000272984300008 PM 19884331 ER PT J AU Chase, JC Bosio, CM AF Chase, Jennifer C. Bosio, Catharine M. TI The Presence of CD14 Overcomes Evasion of Innate Immune Responses by Virulent Francisella tularensis in Human Dendritic Cells In Vitro and Pulmonary Cells In Vivo SO INFECTION AND IMMUNITY LA English DT Article ID LIPOPOLYSACCHARIDE-BINDING PROTEIN; HUMAN MONONUCLEAR PHAGOCYTES; VACCINE STRAIN INFECTION; NECROSIS-FACTOR-ALPHA; ALVEOLAR MACROPHAGES; MURINE MACROPHAGES; EPITHELIAL-CELLS; HUMAN MONOCYTES; BRUCELLA-SUIS; HOST RESPONSE AB Francisella tularensis is a Gram-negative bacterium that causes acute, lethal disease following inhalation. We have previously shown that viable F. tularensis fails to stimulate secretion of proinflammatory cytokines following infection of human dendritic cells (hDC) in vitro and pulmonary cells in vivo. Here we demonstrate that the presence of the CD14 receptor is critical for detection of virulent F. tularensis strain SchuS4 by dendritic cells, monocytes, and pulmonary cells. Addition of soluble CD14 (sCD14) to hDC restored cytokine production following infection with strain SchuS4. In contrast, addition of anti-CD14 to monocyte cultures inhibited the ability of these cells to respond to strain SchuS4. Addition of CD14 or blocking CD14 following SchuS4 infection in dendritic cells and monocytes, respectively, was not due to alterations in phagocytosis or replication of the bacterium in these cells. Administration of sCD14 in vivo also restored cytokine production following infection with strain SchuS4, as assessed by increased concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-12p70, and IL-6 in the lungs of mice receiving sCD14 compared to mock-treated controls. In contrast to homogenous cultures of monocytes or dendritic cells infected in vitro, mice treated with sCD14 in vivo also exhibited controlled bacterial replication and dissemination compared to mock-treated controls. Interestingly, animals that lacked CD14 were not more susceptible or resistant to pulmonary infection with SchuS4. Together, these data support the hypothesis that the absence or low abundance of CD14 on hDC and in the lung contributes to evasion of innate immunity by virulent F. tularensis. However, CD14 is not required for development of inflammation during the last 24 to 48 h of SchuS4 infection. Thus, the presence of this receptor may aid in control of virulent F. tularensis infections at early, but not late, stages of infection. C1 [Chase, Jennifer C.; Bosio, Catharine M.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Bosio, CM (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM bosioc@niaid.nih.gov RI Bosio, Catharine/D-7456-2015 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 66 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2010 VL 78 IS 1 BP 154 EP 167 DI 10.1128/IAI.00750-09 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 535QC UT WOS:000272984300015 PM 19841074 ER PT J AU von Rosenvinge, EC O'Donnell, TG Holland, SM Heller, T AF von Rosenvinge, Erik C. O'Donnell, Thomas G. Holland, Steven M. Heller, Theo TI Chronic Granulomatous Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Letter ID COLITIS C1 [von Rosenvinge, Erik C.; O'Donnell, Thomas G.; Heller, Theo] NIDDKD, NIH, Bethesda, MD 20892 USA. [Holland, Steven M.] NIAID, Bethesda, MD 20892 USA. RP von Rosenvinge, EC (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA DK075008-04] NR 5 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2010 VL 16 IS 1 BP 9 EP 9 DI 10.1002/ibd.20912 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 543LN UT WOS:000273579200005 PM 19322905 ER PT S AU Pham, TD To, CC Wang, HH Zhou, XB AF Pham, Tuan D. To, Cuong C. Wang, Honghui Zhou, Xiaobo BE Pietka, E Kawa, J TI Analysis of Major Adverse Cardiac Events with Entropy-Based Complexity SO INFORMATION TECHNOLOGIES IN BIOMEDICINE, VOL 2 SE Advances in Intelligent and Soft Computing LA English DT Article; Book Chapter ID APPROXIMATE ENTROPY; MASS-SPECTROMETRY; PREDICTION; PHYSIOLOGY; DISEASE; RISK AB Major adverse cardiac events (MACE) are referred to as unsuspected heart attacks that include death, myocardial infarction and target lesion revascularization. Feature extraction and classification methods for such cardiac events are useful tools that can be applied for biomarker discovery to allow preventive treatment and healthy-life maintenance. In this study we present an entropy-based analysis of the complexity of MACE-related mass spectrometry signals, and an effective model for classifying MACE and control complexity-based features. In particular, the geostatistical entropy is analytically rigorous and can provide better information about the predictability of this type of MACE data than other entropy-based methods for complexity analysis of biosignals. Information on the complexity of this type of time-series data can expand our knowledge about the dynamical behavior of a cardiac model and be useful as a novel feature for early prediction. C1 [Pham, Tuan D.; To, Cuong C.] Univ New S Wales, Sch Engn & Informat Technol, Canberra, ACT 2600, Australia. [Wang, Honghui] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Zhou, Xiaobo] Weill Cornell Med Coll, Methodist Hosp Res Inst, Ctr Biotechnol & Informat, Houston, TX 77030 USA. RP Pham, TD (reprint author), Univ New S Wales, Sch Engn & Informat Technol, Canberra, ACT 2600, Australia. EM t.pham@adfa.edu.au; c.to@adfa.edu.au; hwang2@cc.nih.gov; xzhou@tmhs.org NR 21 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1867-5662 BN 978-3-642-13104-2 J9 ADV INTEL SOFT COMPU PY 2010 VL 69 BP 261 EP 272 PG 12 WC Computer Science, Artificial Intelligence SC Computer Science GA BOU32 UT WOS:000277624000027 ER PT S AU Hallenbeck, J AF Hallenbeck, John BE DelZoppo, GJ Gorelick, PB Eisert, W TI How inflammation modulates central nervous system vessel activation and provides targets for intervention-a personal perspective SO INNATE INFLAMMATION AND STROKE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Innate Inflammation as the Common Pathway of Risk Factors Leading to Transient Ischemic Attacks and Stroke: Pathophysiology and Potential Interventions CY MAY 09-11, 2010 CL New York Acad Sci, New York, NY HO New York Acad Sci DE tolerance; stroke; cytokines; immunomodulation; endothelium; E-selectin ID TUMOR-NECROSIS-FACTOR; ISCHEMIC BRAIN-INJURY; SPONTANEOUSLY HYPERTENSIVE-RATS; FOCAL CEREBRAL-ISCHEMIA; FACTOR-ALPHA; E-SELECTIN; TNF-ALPHA; MUCOSAL TOLERANCE; DECOMPRESSION-SICKNESS; SHWARTZMAN REACTION AB I here describe a line of research that grew out of studies of spinal cord-damaging decompression sickness, focused on the blood-endothelial interface, that was influenced by the local Shwartzman phenomenon, addressed innate immune and inflammatory mechanisms, and ultimately arrived at mucosal tolerance approaches to prevent stroke. Intranasal instillation of E-selectin is under development as a novel means of targeting immunomodulation to activating blood vessels within the vascular tree supplying the brain. The goal of this form of focused immunomodulation is to prevent recurrent strokes in patients that have previously suffered transient ischemic attacks or strokes. C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, J (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, 10 Ctr Dr MSC 1401,Bldg 10 Room 5B02, Bethesda, MD 20892 USA. EM hallenbj@ninds.nih.gov FU Intramural NIH HHS [ZIA NS002924-15] NR 39 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 978-1-57331-813-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2010 VL 1207 BP 1 EP 7 DI 10.1111/j.1749-6632.2010.05785.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA BSK36 UT WOS:000284744000002 PM 20955418 ER PT J AU Zhang, XY Huang, J AF Zhang, Xinyue Huang, Jing TI Integrative genome-wide approaches in embryonic stem cell research SO INTEGRATIVE BIOLOGY LA English DT Article ID TRANSCRIPTIONAL REGULATORY CIRCUITRY; SMALL-MOLECULE COMPOUNDS; GENE-EXPRESSION; SELF-RENEWAL; DEVELOPMENTAL REGULATORS; DEFINED FACTORS; SOMATIC-CELLS; MOUSE EMBRYOS; ES CELLS; PLURIPOTENT AB Embryonic stem (ES) cells are derived from blastocysts. They can differentiate into the three embryonic germ layers and essentially any type of somatic cells. They therefore hold great potential in tissue regeneration therapy. The ethical issues associated with the use of human embryonic stem cells are resolved by the technical break-through of generating induced pluripotent stem (iPS) cells from various types of somatic cells. However, how ES and iPS cells self-renew and maintain their pluripotency is still largely unknown in spite of the great progress that has been made in the last two decades. Integrative genome-wide approaches, such as the gene expression microarray, chromatin immunoprecipitation based microarray (ChIP-chip) and chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) offer unprecedented opportunities to elucidate the mechanism of the pluripotency, reprogramming and DNA damage response of ES and iPS cells. This frontier article summarizes the fundamental biological questions about ES and iPS cells and reviews the recent advances in ES and iPS cell research using genome-wide technologies. To this end, we offer our perspectives on the future of genome-wide studies on stem cells. C1 [Zhang, Xinyue; Huang, Jing] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Zhang, XY (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. EM huangj3@mail.nih.gov RI Huang, Jing/A-2566-2009 OI Huang, Jing/0000-0002-7163-5156 FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and Center for Cancer Research. We thank Dr Nan Roche for critically reading the manuscript. NR 64 TC 5 Z9 5 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2010 VL 2 IS 10 BP 510 EP 516 DI 10.1039/c0ib00068j PG 7 WC Cell Biology SC Cell Biology GA 657OW UT WOS:000282423000004 PM 20852801 ER PT J AU Cui, XZ Su, JW Li, Y Shiloach, J Solomon, S Kaufman, JB Mani, H Fitz, Y Weng, J Altaweel, L Besch, V Eichacker, PQ AF Cui, Xizhong Su, Junwu Li, Yan Shiloach, Joseph Solomon, Steven Kaufman, Jeanne B. Mani, Haresh Fitz, Yvonne Weng, Jia Altaweel, Laith Besch, Virginia Eichacker, Peter Q. TI Bacillus anthracis cell wall produces injurious inflammation but paradoxically decreases the lethality of anthrax lethal toxin in a rat model SO INTENSIVE CARE MEDICINE LA English DT Article DE Bacillus anthracis; Cell wall; Cardiopulmonary dysfunction; Cytokine release; Inflammation ID RESPIRATORY-DISTRESS-SYNDROME; INHALATIONAL ANTHRAX; NITRIC-OXIDE; MURAMYL DIPEPTIDE; SEPTIC SHOCK; SEPSIS; PEPTIDOGLYCAN; PATHOPHYSIOLOGY; BIOTERRORISM; PATHOGENESIS AB The in vivo inflammatory effects of the Bacillus anthracis cell wall are unknown. We therefore investigated these effects in rats and, for comparison, those of known inflammatory stimulants, Staphylococcus aureus cell wall or lipopolysaccharide (LPS). Sprague-Dawley rats (n = 103) were challenged with increasing B. anthracis cell wall doses (10, 20, 40, 80, or 160 mg/kg) or diluent (control) as a bolus or 24-h infusion. The three highest bolus doses were lethal (20-64% lethality rates) as were the two highest infused doses (13% with each). Comparisons among lethal or nonlethal doses on other measured parameters were not significantly different, and these were combined for analysis. Over the 24 h after challenge initiation with lethal bolus or infusion, compared to controls, ten inflammatory cytokines and NO levels were increased and circulating neutrophils and platelets decreased (P a parts per thousand currency sign 0.05). Changes with lethal doses were greater than changes with nonlethal doses (P a parts per thousand currency sign 0.01). Lethal bolus or infusion doses produced hypotension or hypoxemia, respectively (P a parts per thousand currency sign 0.05). The effects with B. anthracis cell wall were similar to those of S. aureus cell wall or LPS. However, paradoxically administration of B. anthracis cell wall or LPS decreased the lethality of concurrently administered B. anthracis lethal toxin (P < 0.0001 and 0.04, respectively). B. anthracis cell wall has the potential to produce inflammatory injury during anthrax infection clinically. However, understanding why cell wall or LPS paradoxically reduced lethality with lethal toxin may help understand this toxin's pathogenic effects. C1 [Cui, Xizhong; Su, Junwu; Li, Yan; Solomon, Steven; Fitz, Yvonne; Weng, Jia; Altaweel, Laith; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Shiloach, Joseph; Kaufman, Jeanne B.] NIDDK, NIH, Bethesda, MD 20892 USA. [Mani, Haresh] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Besch, Virginia] NIH, Dept Anesthesiol, Ctr Clin, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 2C148, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov FU Intramural NIH HHS [ZIA CL008091-04] NR 26 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JAN PY 2010 VL 36 IS 1 BP 148 EP 156 DI 10.1007/s00134-009-1643-9 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 544TX UT WOS:000273683300021 PM 19756496 ER PT B AU Sakai, T Onodera, T Yamada, KM AF Sakai, Takayoshi Onodera, Tomohiro Yamada, Kenneth M. BE Sasano, T Suzuki, O TI Cleft formation and branching morphogenesis of salivary gland: exploration of new functional genes SO INTERFACE ORAL HEALTH SCIENCE 2009 LA English DT Proceedings Paper CT 3rd International Symposium for Interface Oral Health Science CY JAN 15-16, 2009 CL Sendai, JAPAN DE salivary gland; branching morphogenesis; cleft formation; molecular analysis; T7-SAGE ID EXPRESSION AB Epithelial branching morphogenesis is important to form many organs. Embryonic salivary glands provide an excellent model for clarifying the mechanisms of this phenomenon. As clefts form, epithelial cell cell adhesions are converted to cell matrix adhesions. Nevertheless, the mechanism of cleft formation is not well understood. Here, we describe a set of approaches being used to identify and characterize molecules necessary for branching morphogenesis. A combination of laser microdissection with T7-SAGE has been established as a gene discovery method for identifying candidate molecules that may be essential for early organ morphogenesis. Progress in understanding the mechanisms of salivary branching morphogenesis will provide novel approaches to future tissue engineering or regeneration of damaged salivary glands. C1 [Sakai, Takayoshi] Osaka Univ, Grad Sch Dent, Dept Oral Facial Disorders, Div Funct Oral Neurosci, 1-8 Yamadaoka, Suita, Osaka 5650871, Japan. [Onodera, Tomohiro; Yamada, Kenneth M.] NIH, Natl Dental & Craniofac Res, Lab Cell, Bethesda, MD 20892 USA. RP Sakai, T (reprint author), Osaka Univ, Grad Sch Dent, Dept Oral Facial Disorders, Div Funct Oral Neurosci, 1-8 Yamadaoka, Suita, Osaka 5650871, Japan. EM sakai@dent.osaka-u.ac.jp NR 11 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 978-4-431-99643-9 PY 2010 BP 13 EP + DI 10.1007/978-4-431-99644-6_2 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BTU47 UT WOS:000288113500002 ER PT J AU Myles, IA AF Myles, Ian A. TI Phantom Rhinitis SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE Aura; Dysosmia; Epilepsy; Neurogenic rhinitis; Olfactory aura; Phantosmia; Refractory rhinitis; Seizures; Temporal lobe ID TEMPORAL-LOBE EPILEPSY; PERCEPTION AB Sensitivity to strong odors has a broad differential diagnosis. A presentation is made of a 60-year-old man with lifelong mild allergic rhinitis and a superimposed 4-year history of sensitivity to smells. He had no response to medical treatments or allergic immunotherapy. His physical examination was unremarkable. After obtaining a detailed history, a definitive imaging study was performed and the patient underwent corrective treatment for his potentially life-threatening disorder. A detailed differential and strong clinical history is sometimes required to uncover the etiology of non-allergic rhinitis. Overwhelming sensations of strong odors may be a sign of a more serious condition and require investigation. This presentation discusses the differential diagnosis and suggested evaluation for patients with abnormalities in olfaction. Copyright (C) 2010 S. Karger AG, Basel C1 NIAID, Dept Allergy & Immunol, NIH, Bethesda, MD 20892 USA. RP Myles, IA (reprint author), NIAID, Dept Allergy & Immunol, NIH, 10-B3-4209,10 Ctr Dr, Bethesda, MD 20892 USA. EM mylesi@niaid.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2010 VL 153 IS 4 BP 424 EP 427 DI 10.1159/000316355 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 683XW UT WOS:000284512600014 PM 20559010 ER PT B AU Dubowitz, H Merrick, J AF Dubowitz, Howard Merrick, Joav BE Dubowitz, H Merrick, J TI ABOUT THE EDITORS SO INTERNATIONAL ASPECTS OF CHILD ABUSE AND NEGLECT SE Health and Human Development LA English DT Article; Book Chapter C1 [Dubowitz, Howard] Univ Maryland, Sch Med, Ctr Families, Baltimore, MD 21201 USA. [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, IL-84105 Beer Sheva, Israel. [Merrick, Joav] Minist Social Affairs, Div Mental Retardat, Jerusalem, Israel. [Merrick, Joav] NICHHD, Bethesda, MD 20892 USA. RP Dubowitz, H (reprint author), Univ Maryland, Sch Med, Ctr Families, Baltimore, MD 21201 USA. 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 978-1-61122-049-0 J9 HEALTH HUM DEV PY 2010 BP 257 EP 257 PG 1 WC Family Studies; Social Work SC Family Studies; Social Work GA BSC59 UT WOS:000284122700025 ER PT S AU Mandell, AJ Selz, KA Aven, J Holroyd, T Coppola, R AF Mandell, Arnold J. Selz, Karen A. Aven, John Holroyd, Tom Coppola, Richard BE In, V Longhini, P Palacios, A TI Daydreaming, Thought Blocking and Strudels in the Taskless, Resting Human Brain's Magnetic Fields SO INTERNATIONAL CONFERENCE ON APPLICATIONS IN NONLINEAR DYNAMICS (ICAND 2010) SE AIP Conference Proceedings LA English DT Proceedings Paper CT International Conference on Applications in Nonlinear Dynamics CY SEP 21-24, 2010 CL Lake Louise, CANADA SP Off Naval Res, Nonlinear Dynam Syst DE MEG; power spectral scaling exponent; topological and metric entropies; intermittent vorticity; wavelet transformation; MEG eigenfunction; petite absence epilepsy; dynamical systems; ergodic single orbit measures ID DYNAMICAL-SYSTEMS; CHAOTIC FLOWS; DYNAMOS; SUPPRESSION; ENTROPY; FLUID AB The incidence, i(S), and duration, l(S), of transient, intermittent, hierarchical vorticities, strudels,S, in magnetic flux fluctuations, were computed from MEG records. from 91 task-free resting subjects. The MEG's i(S) and l(S) manifested characteristic times and entropic sensitivity resembling those reported in psychological studies of daydreaming and task-unrelated thoughts, TUTs. Transient reduction or absences of strudels can be found in patients with syndromes characterized by thought blocking. Positive ergodic single orbit measures of expansiveness and mixing predict i(S) and l(S). An analogy with the relationship between intermittent pontine-geniculate-occipital waves and dreaming is made to strudels with daydreaming. Both can be interpreted as neurophysiological correlates of the spontaneous intrusions into consciousness of the never idle unconscious mind. C1 [Mandell, Arnold J.; Aven, John; Holroyd, Tom; Coppola, Richard] NIMH, NIMH Core MEG Facil, Bldg 10, Bethesda, MD 20892 USA. [Mandell, Arnold J.; Selz, Karen A.] Cielo Inst, Asheville, NC 28804 USA. [Aven, John] NIMH, Bethesda, MD USA. RP Mandell, AJ (reprint author), NIMH, NIMH Core MEG Facil, Bldg 10, Bethesda, MD 20892 USA. FU Fetzer-Franklin Trust; DARPA (Microelectronics); Space and Naval Warfare Center FX This work was supported by the Fetzer-Franklin Trust, DARPA (Microelectronics) and the Space and Naval Warfare Center. Appreciation is expressed to Michael Shlesinger, Harold Puthoff, Paul Gailey, Markus Tino Procida , John Steill, Mark George, Fred Carver, and Judy Mitchell-Francis for their insights, advice and aid. NR 45 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0894-4 J9 AIP CONF PROC PY 2010 VL 1339 BP 7 EP + DI 10.1063/1.3574840 PG 4 WC Physics, Applied SC Physics GA BVJ04 UT WOS:000291631600001 ER PT S AU Aven, JL Mandell, AJ Holroyd, T Coppola, R AF Aven, John L. Mandell, Arnold J. Holroyd, Tom Coppola, Richard BE In, V Longhini, P Palacios, A TI Complexity of the Task less Mind at Different Time-Scales: an Empirically Weighted Approach to Decomposition and Measurement SO INTERNATIONAL CONFERENCE ON APPLICATIONS IN NONLINEAR DYNAMICS (ICAND 2010) SE AIP Conference Proceedings LA English DT Proceedings Paper CT International Conference on Applications in Nonlinear Dynamics CY SEP 21-24, 2010 CL Lake Louise, CANADA SP Off Naval Res, Nonlinear Dynam Syst DE Empirical Mode Decomposition; Magnetoencephalography; Entropy; Time-Frequency Analysis AB The neurodynamical state of an eyes closed at 'rest' subject is an area of keen interest in the neuroscience community due to Raichle's field changing concept of the Default Mode Network [1]. The dynamic analysis of neurobiologically derived data commonly involves the computation of distributional measures and time-frequency transforms, and more recently the use of ergodic measures. However, many of the methods used in these computations rely upon questionable assumptions such as stationarity or approximate linearity. The Empirical Mode Decomposition of Huang et al., [2], which preserves nonlinearity and non-stationarity, has led to alternative signal processing techniques. We append to this growing set of techniques a well-defined class of Weighting Functionals, WF. The strength is that they are easily applied to any number of time-frequency transforms and ergodic/complexity measurements because the WFs rescale all the results according to the proportion of energy contained at the individual time-scales. The application to ergodic/complexity measurements has not been addressed in the context of Intrinsic Mode Functions, and is done so here for the first time. Our interest is to take these methods and demonstrate time dependence of the signal across multiple time-scales in the comparison of normal controls and a variety of psychopathological and neuropathological conditions. C1 [Aven, John L.] Fetzer Franklin Fellow Consciousness Studies NIMH, Bethesda, MD 20892 USA. [Mandell, Arnold J.] Cielo Inst, Asheville, NC 28804 USA. [Holroyd, Tom; Coppola, Richard] NIMH Core, MEG Facil, Bethesda, MD USA. RP Aven, JL (reprint author), Fetzer Franklin Fellow Consciousness Studies NIMH, Bethesda, MD 20892 USA. EM chaotic_aven@yahoo.com FU post-doctoral fellowship at the NIMH Core MEG Laboratory from the Fetzer-Franklin Trust FX John Aven was supported by a post-doctoral fellowship at the NIMH Core MEG Laboratory from the Fetzer-Franklin Trust. NR 10 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0894-4 J9 AIP CONF PROC PY 2010 VL 1339 BP 275 EP + DI 10.1063/1.3574863 PG 2 WC Physics, Applied SC Physics GA BVJ04 UT WOS:000291631600024 ER PT J AU Spolski, R Leonard, WJ AF Spolski, Rosanne Leonard, Warren J. TI IL-21 and T follicular helper cells SO INTERNATIONAL IMMUNOLOGY LA English DT Review DE autoimmunity; BCL6; germinal center; T(h) subsets ID SYSTEMIC AUTOIMMUNITY; B-CELLS; C-MAF; CYTOKINE; DIFFERENTIATION; INTERLEUKIN-21; ICOS; GENERATION; EXPRESSION; RECEPTOR AB Upon encounter with antigen, CD4(+) T cells differentiate into effector T(h) subsets with distinctive functions that are related to their unique cytokine profiles and anatomical locations. One of the most important T(h) functions is to provide signals to developing B cells that induce specific and appropriate antibody responses. The major CD4(+) T cell subset that helps B cells is the T follicular helper (T(FH)) cell, whose expression of the chemokine receptor CXCR5 [chemokine (C-X-C motif) receptor 5] serves to localize this cell to developing germinal centers (GCs) where it provides instructive signals leading to Ig class switching and somatic mutation. T(FH) cells produce high levels of IL-21, a cytokine that is critical for GC formation and also for the generation of T(FH) cells. Although T(FH) cells have been found to produce cytokines characteristic of other T(h) subsets, they represent a distinct lineage whose development is driven by the transcription factor B-cell CLL lymphoma-6 (BCL6). Consistent with their critical role in the generation of antibody responses, dysregulated T(FH) function has been associated with the development of systemic autoimmunity. Here, we review the role of IL-21 in the regulation of normal T(FH) development and function as well as in progression of autoimmune responses. C1 [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, Bldg 10,Room 7B05, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health FX Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. NR 43 TC 60 Z9 68 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 2010 VL 22 IS 1 BP 7 EP 12 DI 10.1093/intimm/dxp112 PG 6 WC Immunology SC Immunology GA 534XO UT WOS:000272931000002 PM 19933709 ER PT J AU Drake, SK Hortin, GL AF Drake, Steven K. Hortin, Glen L. TI Improved detection of intact tyrosine sulfate-containing peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in linear negative ion mode SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Tyrosine sulfation; Post-translational modification; MALDI TOF mass spectrometry; Bioactive peptides; alpha(2)-Antiplasmin sulfation ID POSTTRANSLATIONAL MODIFICATION; HUMAN-COMPLEMENT; AMINO-TERMINUS; 4TH COMPONENT; FACTOR-VIII; PROTEINS; IDENTIFICATION; RESIDUES; SITES; SULFOTYROSINE AB Sulfation of tyrosine residues is a common post-translational modification, but detecting and quantitating this modification poses challenges due to lability of the sulfate group. The goal of our studies was to determine how best to detect and to assess the stoichiometry of this modification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). Sulfated and nonsulfated forms of peptides-hirudin(55-65), caerulein, and cholecystokinin octapeptide and phosphorylated and nonphosphorylated pp60-c-src (521-533)-were analyzed using several matrices: sinapinic acid (SA), 2,5-dihydroxybenzoic acid (DBA), and cyano-4-hydroxycinnamic acid (CHCA). Intact sulfated peptides were difficult to detect using positive ion mode; peptides were observed as desulfated ions. Phosphorylated peptide was stable and was detected in positive and negative ion modes. Detection of sulfated peptides improved with: (1) Analysis in negative ion mode, (2) Decreased laser power, (3) Matrix selection: DBA >= SA > CHCA. In negative ion mode, desorption/ionization of sulfated peptide was equivalent or more efficient than nonsulfated peptide, depending on conditions of analysis. Examination of a tryptic digest Of alpha(2)-antiplasmin detected the single site of sulfation in negative ion mode but not in positive ion mode. We conclude that improved detection of sulfated peptides can be achieved in negative ion mode. Dual analysis in positive and negative ion modes serves as a potential means of identifying peptides with labile modifications such as sulfation and distinguishing them from phosphorylation. (C) 2009 Published by Elsevier Ltd. C1 [Drake, Steven K.] NIH, Dept Crit Care Med, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Hortin, Glen L.] NIH, Dept Lab Med, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), Univ Florida, Dept Pathol, POB 100275, Gainesville, FL 32610 USA. EM ghortin@pathology.ufl.edu FU Clinical Center, National Institutes of Health, U.S. Department of Health and Human Services FX Studies were supported by the intramural research program of the Clinical Center, National Institutes of Health, U.S. Department of Health and Human Services. NR 48 TC 9 Z9 9 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD JAN PY 2010 VL 42 IS 1 BP 174 EP 179 DI 10.1016/j.biocel.2009.10.018 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547TN UT WOS:000273912200023 PM 19857600 ER PT J AU Liang, HS Zhong, YH Luo, ZJ Huang, Y Lin, HD Luo, M Zhan, S Xie, KQ Ma, Y Li, QQ AF Liang, Huasheng Zhong, Yuhua Luo, Zuojie Huang, Yu Lin, Huade Luo, Min Zhan, Song Xie, Kaiqing Ma, Yan Li, Qingdi Quentin TI Assessment of biomarkers for clinical diagnosis of papillary thyroid carcinoma with distant metastasis SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Article DE Papillary thyroid cancer; Diagnosis; Biomarkers; VEGF-C; bFGF; Metastasis; Immunohistochemistry ID CYCLE REGULATORY PROTEINS; E-CADHERIN EXPRESSION; GROWTH-FACTOR-C; SERUM THYROGLOBULIN; IMMUNOHISTOCHEMICAL EXPRESSION; FOLLICULAR CARCINOMA; PROGNOSTIC VALUE; CANCER; TUMORS; CXCR4 AB Early diagnosis and treatment of thyroid cancers are critical for better prognosis and better survival rates. The purpose of this study was to identify potential diagnostic markers for papillary thyroid carcinomas with distant metastasis. Fifty-eight papillary thyroid tumor specimens (27 papillary thyroid carcinomas with distant metastasis and 31 without metastasis) were examined, and protein expression of pituitary tumor-transforming gene (PTTG), E-cadherin, p27kip1, vascular endothelial growth factor (VEGF)-C, metalloproteinase (MMP) 2, MMP9, chemokine receptor CXCR4, and basic fibroblast growth factor (bFGF) in these tumors was assessed by immunohistochemistry. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and their diagnostic values were evaluated by ROC curve analysis. PTTG, VEGF-C, MMP2, MMP9, CXCR4, and bFGF were overexpressed in metastatic papillary thyroid carcinomas, whereas p27kip1 expression was elevated only in carcinomas lacking metastasis. Multiple-factor binary ordinal logistic regression analysis revealed that PTTG, VEGF-C, MMP2, and bFGF were independently related to biological metastatic behavior in thyroid tumors, suggesting their potential use as biomarkers. ROC curve analysis showed that among these four proteins, VEGF-C and bFGF were the best diagnostic biomarkers. A VEGF-C and bFGF cluster was the most useful factor for the differential diagnosis between metastatic and non-metastatic papillary thyroid cancers. Thus, the combined use of VEGF-C and bFGF as biomarkers may improve the diagnostic accuracy of papillary thyroid carcinoma and may be useful in multimodal screening programs for the clinical diagnosis of papillary thyroid carcinoma and early detection of papillary thyroid carcinoma with distant metastasis. (Int J Biol Markers 2010; 25: 38-45) C1 [Li, Qingdi Quentin] NIAID, NIH, Bethesda, MD 20892 USA. [Liang, Huasheng; Zhong, Yuhua; Zhan, Song] Guangxi Med Univ, Affiliated Hosp 9, Dept Endocrinol, Beihai, Peoples R China. [Luo, Zuojie] Guangxi Med Univ, Univ Hosp 1, Dept Endocrinol, Nanning, Peoples R China. [Ma, Yan] Guangxi Med Univ, Univ Hosp 1, Dept Ultrasound Diag, Nanning, Peoples R China. [Liang, Huasheng; Xie, Kaiqing] So Med Univ, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China. [Huang, Yu] Guangxi Prov Hosp, Dept Hepatobiliary & Endocrine Surg, Nanning, Peoples R China. [Lin, Huade] Pingnan Hosp, Dept Hepatobiliary & Endocrine Surg, Pingnan, Peoples R China. [Luo, Min] Shanghai Endocrine & Metab Res Inst, Shanghai, Peoples R China. RP Li, QQ (reprint author), NIAID, NIH, Bldg 10,Room 11 N234, Bethesda, MD 20892 USA. EM zluo888@yahoo.com.cn; liquenti@niaid.nih.gov FU Science and Technology Commission Foundation of Guangxi [0339080]; Science Foundation for Youths of Guangxi [0728108]; Department of Health and Human Services of Guangxi [200991] FX This study was supported by grants from the Applied and Basic Research Programs of the Science and Technology Commission Foundation of Guangxi (No. 0339080), the Science Foundation for Youths of Guangxi (No. 0728108), and the Key Research Programs of the Department of Health and Human Services of Guangxi (No. 200991). NR 35 TC 18 Z9 19 U1 0 U2 6 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD JAN-MAR PY 2010 VL 25 IS 1 BP 38 EP 45 PG 8 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 607BJ UT WOS:000278473000006 PM 20306451 ER PT J AU Sheng-Fowler, L Cai, F Fu, HQ Zhu, Y Orrison, B Foseh, G Blair, DG Hughes, SH Coffin, JM Lewis, AM Peden, K AF Sheng-Fowler, Li Cai, Fang Fu, Haiqing Zhu, Yong Orrison, Brian Foseh, Gideon Blair, Don G. Hughes, Stephen H. Coffin, John M. Lewis, Andrew M., Jr. Peden, Keith TI Tumors Induced in Mice by Direct Inoculation of Plasmid DNA Expressing Both Activated H-ras and c-myc SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE H-ras; c-myc; oncogenes ID TUMORIGENIC CONVERSION; CHROMOSOMAL INSERTION; EMBRYO FIBROBLASTS; CELLULAR DNA; FOREIGN DNA; MICRORNAS; ONCOGENES; CARCINOGENESIS; TRANSFORMATION; CANCER AB Vaccines contain residual DNA derived from the cells used to produce them. As part of our investigation to assess the risk of this cellular DNA, we are developing a quantitative in vivo assay to assess the oncogenicity of DNA. In an earlier study, we had generated expression plasmids for two oncogenes - human activated T24-H-ras and murine c-myc - and had shown that these two plasmids, pMSV-T24-H-ras and pMSV-c-myc, could act in concert to induce tumors in mice, although the efficiency was low. In this study, we took two approaches to increase the oncogenic efficiency: 1) both oncogene-expression cassettes were placed on the same plasmid; 2) transfection facilitators, which increase DNA uptake and expression in vitro, were tested. The dual-expression plasmid, pMSV-T24-H-ras/MSV-c-myc, is about 20-fold more efficient at tumor induction in newborn NIH Swiss mice than the separate expression plasmids, with tumors being induced with 1 mu g of the dual-expression plasmid DNA. However, none of the transfection facilitators tested increased the efficiency of tumor induction. Based on these data, the dual-expression plasmid pMSV-T24-H-ras/MSV-c-myc will be used as the positive control to develop a sensitive and quantitative animal assay that can be used to assess the oncogenic activity of DNA. C1 [Sheng-Fowler, Li; Cai, Fang; Fu, Haiqing; Zhu, Yong; Orrison, Brian; Foseh, Gideon; Lewis, Andrew M., Jr.; Peden, Keith] US FDA, Div Viral Prod, OVRR, CBER, Bethesda, MD 20892 USA. [Blair, Don G.; Hughes, Stephen H.; Coffin, John M.] NCI, Frederick Canc Res Facil, Frederick, MD 21702 USA. [Blair, Don G.] Tufts Univ, Boston, MA 02111 USA. RP Peden, K (reprint author), US FDA, Div Viral Prod, OVRR, CBER, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. EM andrew.lewis@fda.hhs.gov; keith.peden@fda.hhs.gov FU Office of the Commissioner, FDA; National Vaccine Program Office; National Institute of Allergy and Infectious Diseases; NIAID; National Institutes of Health, National Cancer Institute, Center for Cancer Research; American Cancer Society; George Kirby Foundation FX This work was initiated following support from a grant from the Office of the Commissioner, FDA. Additional support came from a grant from the National Vaccine Program Office; current work is supported by a contract from the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases through an Interagency Agreement with CBER/FDA. F. C., H. F. and Y.Z. were supported by the NIAID contract. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (to S. H. H). JMC was a research Professor of the American Cancer Society, with support from the George Kirby Foundation. We thank Hana Golding, Arifa Khan, Jerry Weir, Phil Krause, and Robin Levis for discussions and/or comments on the manuscript. NR 37 TC 5 Z9 6 U1 0 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 2 BP 151 EP 162 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 586AT UT WOS:000276873800004 PM 20376206 ER PT J AU Su, N Xu, XL Li, CL He, QF Zhao, L Li, C Chen, SY Luo, FT Yi, LX Du, XL Huang, HY Deng, CX Chen, L AF Su, Nan Xu, Xiaoling Li, Cuiling He, Qifen Zhao, Ling Li, Can Chen, Siyu Luo, Fengtao Yi, Lingxian Du, Xiaolan Huang, Haiyang Deng, Chuxia Chen, Lin TI Generation of Fgfr3 Conditional Knockout Mice SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE FGFR3; conditional knock out; Cre-Loxp; gene targeting ID GROWTH-FACTOR RECEPTOR-3; SKELETAL OVERGROWTH; BONE-DEVELOPMENT; ACHONDROPLASIA; MUTATIONS; GENE; DWARFISM; MOUSE; DIFFERENTIATION; DEFECTS AB Fibroblast growth factor receptor 3 (FGFR3), highly conserved in both humans and murine, is one of key tyrosine kinase receptors for FGF. FGFR3 is expressed in different tissues, including cartilage, brain, kidney, and intestine at different development stages. Conventional knockout of Fgfr3 alleles leads to short life span, and overgrowth of bone. In clinic, human FGFR3 mutations are responsible for three different types of chondrodysplasia syndromes including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD). For better understanding of the roles of FGFR3 in different tissues at different stages of development and in pathological conditions, we generated Fgfr3 conditional knockout mice in which loxp sites flank exons 9-10 in the Fgfr3 allele. We also demonstrated that Cre-mediated recombination using Col2a1-Cre, a Cre line expressed in chondrocyte during bone development, results in specific deletion of the gene in tissues containing cartilage. This animal model will be useful to study distinct roles of FGFR3 in different tissues at different ages. C1 [Su, Nan; He, Qifen; Zhao, Ling; Li, Can; Chen, Siyu; Luo, Fengtao; Yi, Lingxian; Du, Xiaolan; Huang, Haiyang; Chen, Lin] Third Mil Med Univ, Inst Surg Res, Trauma Ctr,Daping Hosp, State Key Lab Trauma Burns & Combined Injury, Chongqing 400042, Peoples R China. [Xu, Xiaoling; Li, Cuiling; Deng, Chuxia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Chen, L (reprint author), Third Mil Med Univ, Inst Surg Res, Trauma Ctr,Daping Hosp, State Key Lab Trauma Burns & Combined Injury, Chongqing 400042, Peoples R China. EM chuxiad@bdg10.niddk.nih.gov; linchen70@163.com RI deng, chuxia/N-6713-2016 FU Special Funds for Major State Basic Research Program of China (973 program) [2005CB522604]; National Natural Science Foundation of China [30425023, 30530410, 30901527] FX We thank Xiao Yang for EIIa-Cre and Col2a1-Cre transgenic mice. The work was supported by the Special Funds for Major State Basic Research Program of China (973 program) (No. 2005CB522604), National Natural Science Foundation of China (No. 30425023, No. 30530410, No. 30901527). NR 26 TC 15 Z9 15 U1 1 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 4 BP 327 EP 332 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 632ZO UT WOS:000280468900003 PM 20582225 ER PT J AU Kluk, BJ Fu, YB Formolo, TA Zhang, L Hindle, AK Man, YG Siegel, RS Berg, PE Deng, CX McCaffrey, TA Fu, SW AF Kluk, Brian J. Fu, Yebo Formolo, Trina A. Zhang, Lei Hindle, Anne K. Man, Yan-gao Siegel, Robert S. Berg, Patricia E. Deng, Chuxia McCaffrey, Timothy A. Fu, Sidney W. TI BP1, an Isoform of DLX4 Homeoprotein, Negatively Regulates BRCA1 in Sporadic Breast Cancer SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE BP1; DLX4; homeoprotein; BRCA1; breast cancer ID BETA-GLOBIN GENE; HOMEOBOX GENE; OVARIAN-CANCER; EXPRESSION; CELLS; IDENTIFICATION; METHYLATION; CENTROSOME; PROMOTER; REGION AB Introduction: Several lines of evidence point to an important role for BPI, an isoform of DLX4 homeobox gene, in breast carcinogenesis and progression. BRCAI is a well-known player in the etiology of breast cancer. While familial breast cancer is often marked by BRCAI mutation and subsequent loss of heterozygosity, sporadic breast cancers exhibit reduced expression of wild type BRCAI, and loss of BRCAI expression may result in tumor development and progression. Methods: The Cister algorithm and Genomatix program were used to identify potential BPI binding sites in BRCAI gene. Real-time PCR, Western blot and immunohistochemistry analysis were performed to verify the expression of BRCAI and BPI in cell lines and breast cancer tissues. Double-stranded siRNA transfection was carried out for silencing BPI expression. ChIP and EMSA were used to confirm that BPI specifically binds to BRCAI. Results: A putative BPI binding site was identified in the first intron of BRCAI, which was confirmed by chromatin immunoprecipiation and electrophoresis mobility shift assay. BPI and BRCAI expression were inversely correlated in breast cancer cell lines and tissues, suggesting that BPI may suppress BRCAI transcription through consensus sequence binding. Conclusions: BPI homeoprotein represses BRCAI expression through direct binding to its first intron, which is consistent with a previous study which identified a novel transcriptional repressor element located more than 500 base pairs into the first intron of BRCAI, suggesting that the first intron plays an important role in the negative regulation of BRCAI. Although further functional studies are necessary to confirm its repress or activity towards BRCAI, the elucidation of the role of BPI in breast tumorigenesis holds great promise in establishing BPI as a novel target for drug therapy. C1 [Kluk, Brian J.; Fu, Yebo; Formolo, Trina A.; McCaffrey, Timothy A.; Fu, Sidney W.] George Washington Univ, Med Ctr, Dept Med, Div Genom Med, Washington, DC 20037 USA. [Zhang, Lei] Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Hindle, Anne K.] George Washington Univ, Med Ctr, Dept Anesthesiol, Washington, DC 20037 USA. [Man, Yan-gao] Armed Forces Inst Pathol, Washington, DC 20306 USA. [Siegel, Robert S.] George Washington Univ, Med Ctr, Div Hematol & Oncol, Dept Med, Washington, DC 20037 USA. [Berg, Patricia E.] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Deng, Chuxia] NIH, Mammalian Genet Sect, Bethesda, MD 20892 USA. RP Fu, SW (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Genom Med, 2300 1st St NW,Room 523A, Washington, DC 20037 USA. EM sfu@gwu.edu RI deng, chuxia/N-6713-2016 FU NIH [CA102928 (SWF)]; McCormick Genomics Grant (SWF). FX We would like to thank the support from Dr. Alan Wasserman, Chairman of the Department of Medicine and Dr. Allan Goldstein, former Chairman of the Department of Biochemistry and Molecular Biology. This work was supported by NIH grant CA102928 (SWF) and the McCormick Genomics Grant (SWF). NR 39 TC 9 Z9 11 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 5 BP 513 EP 524 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 651WV UT WOS:000281959000010 PM 20877436 ER PT J AU Azhar, M Wang, PY Frugier, T Koishi, K Deng, CX Noakes, PG McLennan, IS AF Azhar, Mohamad Wang, Pei-Yu Frugier, Tony Koishi, Kyoko Deng, Chuxia Noakes, Peter G. McLennan, Ian S. TI Myocardial deletion of Smad4 using a novel alpha skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE heart; myogenesis; transforming growth factor beta; SMAD; Marfan syndrome ID GROWTH-FACTOR-BETA; EPITHELIAL-MESENCHYMAL TRANSITION; ENDOCARDIAL CUSHION; HEART DEVELOPMENT; CARDIOVASCULAR-SYSTEM; VALVE DEVELOPMENT; KNOCKOUT MICE; RECEPTOR; DEFECTS; DIFFERENTIATION AB SMAD4 acts as the converging point for TGF beta and BMP signaling in heart development. Here, we investigated the role of SMAD4 in heart development using a novel a skeletal muscle actin Cre recombinase (MuCre) transgenic mouse strain. Lineage tracing using MuCre/ROSA26(LacZ) reporter mice indicated strong Cre-recombinase expression in developing and adult heart and skeletal muscles. In heart development, significant MuCre expression was noted at E11.5 in the atrial, ventricular, outflow tract and atrioventricular canal myocardium, but not in the endocardial cushions. MuCre-driven conditional deletion of Smad4 in mice caused double outlet right ventricle (DORV), ventricular septal defect (VSD), impaired trabeculation and thinning of ventricular myocardium, and mid-gestational embryonic lethality. In conclusion, MuCre mice effectively delete genes in both heart and skeletal muscles, thus enabling the discovery that myocardial Smad4 deletion causes misalignment of the outflow tract and DORV. C1 [Azhar, Mohamad] Univ Arizona, Dept Cell Biol & Anat, Tucson, AZ 85724 USA. [Azhar, Mohamad] Univ Arizona, Inst BIO5, Tucson, AZ 85724 USA. [Wang, Pei-Yu; Frugier, Tony; Koishi, Kyoko; McLennan, Ian S.] Univ Otago, Brain Hlth & Repair Res Ctr, Dept Anat & Struct Biol, Dunedin, New Zealand. [Wang, Pei-Yu] Natl Chengchi Univ, Res Ctr Mind Brain & Learning, Taipei 116, Taiwan. [Wang, Pei-Yu] Natl Chengchi Univ, Inst Neurosci, Taipei 116, Taiwan. [Frugier, Tony] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. [Frugier, Tony] Alfred Hosp, Natl Trauma Res Inst, Melbourne, Vic 3004, Australia. [Deng, Chuxia] NIDDK, GDDB, NIH, Bethesda, MD 20892 USA. [Noakes, Peter G.] Univ Queensland, Queensland Brain Inst, Sch Biomed Sci, Brisbane, Qld 4072, Australia. RP Azhar, M (reprint author), 1656 E Mabel St,POB 245217, Tucson, AZ 85724 USA. EM azharm@email.arizona.edu RI deng, chuxia/N-6713-2016; OI WANG, PEI-YU/0000-0002-1792-8935; Frugier, Tony/0000-0002-1275-5158 FU Royal Society of New Zealand; Arizona Biomedical Research Commission; Steven M. Gootter Foundation; Stephen Michael Schneider Investigator Award for Pediatric Cardiovascular Research; NHMRC Australia; William J. "Billy" Gieszl Endowment for Heart Research; [R01 HL92508] FX The skilled technical assistance of Mrs. Batchelor is gratefully acknowledged. Dr Edna C. Hardeman and Prof. Pierre Chambon are thanked for, respectively, gifting the alpha-skeletal actin promoter and Cre recombinase-ERT gene. This work was supported by the Marsden Fund Royal Society of New Zealand (I.S.M.), The Arizona Biomedical Research Commission (M.A.), The Steven M. Gootter Foundation (M.A.), The Stephen Michael Schneider Investigator Award for Pediatric Cardiovascular Research (M.A.), The William J. "Billy" Gieszl Endowment for Heart Research (M.A.), and R01 HL92508 (M.A.), and NHMRC Australia (PGN). NR 55 TC 12 Z9 13 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 6 BP 546 EP 555 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 677LD UT WOS:000283993000003 PM 20877696 ER PT J AU Li, CL Li, YP Fu, XY Deng, CX AF Li, Cuiling Li, Yi-Ping Fu, Xin-Yuan Deng, Chu-Xia TI Anterior Visceral Endoderm SMAD4 Signaling Specifies Anterior Embryonic Patterning and Head Induction in Mice SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE TGF-beta; SMAD4; AVE; epiblast; mesoderm patterning ID CONDITIONAL KNOCKOUT MICE; SQUAMOUS-CELL CARCINOMA; EARLY MOUSE EMBRYO; STEM-CELLS; TARGETED DISRUPTION; MESODERM INDUCTION; JUVENILE POLYPOSIS; GENE-EXPRESSION; GASTRULATION; SKIN AB SMAD4 serves as a common mediator for signaling of TGF-beta superfamily. Previous studies illustrated that SMAD4-null mice die at embryonic day 6.5 (E6.5) due to failure of mesoderm induction and extraembryonic defects; however, functions of SMAD4 in each germ layer remain elusive. To investigate this, we disrupted SMAD4 in the visceral endoderm and epiblast, respectively, using a Cre-loxP mediated approach. We showed that mutant embryos lack of SMAD4 in the visceral endoderm (Smad4(Co/Co);TTR-Cre) died at E7.5-E9.5 without head-fold and anterior embryonic structures. We demonstrated that TGF-beta regulates expression of several genes, such as Hex1, Cer1, and Lim1, in the anterior visceral endoderm (AVE), and the failure of anterior embryonic development in Smad4Co/Co; TTR-Cre embryos is accompanied by diminished expression of these genes. Consistent with this finding, SMAD4-deficient embryoid bodies showed impaired responsiveness to TGF-beta-induced gene expression and morphological changes. On the other hand, embryos carrying Cre-loxP mediated disruption of SMAD4 in the epiblasts exhibited relatively normal mesoderm and head-fold induction although they all displayed profound patterning defects in the later stages of gastrulation. Cumulatively, our data indicate that SMAD4 signaling in the epiblasts is dispensable for mesoderm induction although it remains critical for head patterning, which is significantly different from SMAD4 signaling in the AVE, where it specifies anterior embryonic patterning and head induction. C1 [Li, Cuiling; Deng, Chu-Xia] NIDDK, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Li, Yi-Ping] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Fu, Xin-Yuan] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore. RP Deng, CX (reprint author), NIDDK, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA FX We thank Dr. T Mak for providing Smad4-/- ES cells, and members of Dr. Deng lab for their critical discussion of this work. This work was supported by the Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA. NR 53 TC 2 Z9 2 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 6 BP 569 EP 583 PG 15 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 677LD UT WOS:000283993000005 PM 20941375 ER PT J AU Wang, RH Li, CL Deng, CX AF Wang, Rui-Hong Li, Cuiling Deng, Chu-Xia TI Liver Steatosis and Increased ChREBP Expression in Mice Carrying a Liver Specific SIRT1 Null Mutation under a Normal Feeding Condition SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE SIRT1; SREBP-1c; ChREBP; fatty liver; mice ID FATTY LIVER; INSULIN-RESISTANCE; HEPATIC STEATOSIS; TUMOR-SUPPRESSOR; GENE-EXPRESSION; SIRTUINS; METABOLISM; DISEASE; PROTEIN; MOUSE AB SIRT1, a homolog of yeast Sir2, is a type III NAD+ dependent histone and protein deacetylase. Previous studies of mice carrying liver specific deletion of exon 4 of the Sirt1 gene revealed opposite responses of mutant mice to a high-fat diet in terms of fatty liver formation, which obscures the function of SRIT1 in liver development and lipid metabolism. To investigate this, we deleted exons 5 and 6 of Sirt1 in the liver by using a Cre-loxP approach. Western blot using an antibody to N-terminal SIRT1 does not detect a truncated protein in the liver of the mutant mice (Sirt1(flox5-6/flox5-6); Alb-Cre), suggesting a null mutation for SIRT1 is generated in the liver. Unlike the previously reported phenotypes, the Sirt1(flox5-6/flox5-6);Alb-Cre mice develop fatty liver under a normal feeding condition. The disease starts at two months of age and incidence increases as the animals become older, affecting 78% of them when they are over one year of age. We showed that the steatosis is accompanied by altered expression of a number of genes, including increased expression of ChREBP, which acts as one of the central determinants of lipid synthesis in the liver. This data uncovers an important role of SIRT1 in regulating lipid metabolism in the liver, and the SIRT1 mutant mice may serve as an animal model for studying human fatty liver disease and facilitate the development of effective therapeutic approach for the disease. C1 [Wang, Rui-Hong; Li, Cuiling; Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA FX We thank members of Deng lab for their helpful discussion of this work and Dr. Cristine Chisholm for critical reading of this manuscript. This work was supported by the Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA. NR 28 TC 42 Z9 45 U1 0 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 7 BP 682 EP 690 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 700UU UT WOS:000285770600008 PM 21103071 ER PT J AU Yang, JA AF Yang, Jian TI Role of clusters in insulin-regulated GLUT4 trafficking in adipose cells: A new paradigm? SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Editorial Material DE Adipocyte; GLUT4; exocytosis; endocytosis; insulin resistance ID PLASMA-MEMBRANE; GLUCOSE-TRANSPORT; TRANSLOCATION; FUSION; VESICLES AB Insulin stimulates glucose transport in muscle and adipose cells by stimulating translocation of glucose transporter 4 (GLUT4) to the plasma membrane. In a recent Cell Metabolism paper, Stenkula et al. found that insulin controls the spatial distribution of GLUT4 on the surface of isolated adipose cells through regulation of their post-fusion dispersal. The presence of GLUT4 in plasma membrane-associated clusters is suggestive of a new paradigm in membrane protein recycling. C1 [Yang, Jian] NIDDK, EDMNS, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Yang, Jian] Univ S Alabama, Coll Med, Dept Physiol, Mobile, AL 36688 USA. RP Yang, JA (reprint author), NIDDK, EDMNS, Diabet Branch, NIH, Bethesda, MD 20892 USA. EM jian.yang@nih.gov NR 10 TC 3 Z9 3 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 7 BP 716 EP 718 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 700UU UT WOS:000285770600011 PM 21152264 ER PT J AU Zheng, ZM AF Zheng, Zhi-Ming TI Viral Oncogenes, Noncoding RNAs, and RNA Splicing in Human Tumor Viruses SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE Human papillomaviruses; Epstein-Barr virus; Kaposi sarcoma-associated herpesvirus; adenovirus; polyomavirus; human T-cell leukemia virus; viral noncoding RNA; viral microRNA; RNA splicing ID EPSTEIN-BARR-VIRUS; HUMAN-PAPILLOMAVIRUS TYPE-16; T-CELL LEUKEMIA; SARCOMA-ASSOCIATED HERPESVIRUS; PRE-MESSENGER-RNA; CHRONIC-FATIGUE-SYNDROME; MEMBRANE-PROTEIN 1; HEPATITIS-B-VIRUS; MAMMARY EPITHELIAL-CELLS; HUMAN GAMMA-HERPESVIRUSES AB Viral oncogenes are responsible for oncogenesis resulting from persistent virus infection. Although different human tumor viruses express different viral oncogenes and induce different tumors, their oncoproteins often target similar sets of cellular tumor suppressors or signal pathways to immortalize and/or transform infected cells. Expression of the viral E6 and E7 oncogenes in papillomavirus, E1A and E1B oncogenes in adenovirus, large T and small t antigen in polyomavirus, and Tax oncogene in HTLV-1 are regulated by alternative RNA splicing. However, this regulation is only partially understood. DNA tumor viruses also encode noncoding RNAs, including viral microRNAs, that disturb normal cell functions. Among the determined viral microRNA precursors, EBV encodes 25 from two major clusters (BART and BHRF1), KSHV encodes 12 from a latent region, human polyomavirus MCV produce only one microRNA from the late region antisense to early transcripts, but HPVs appears to produce no viral microRNAs. C1 NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU H, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. I thank Dr. John Taylor and Dr. Christophe Nicot of University of Kansas Medical Center for their generous permission of figure modification. NR 273 TC 36 Z9 36 U1 0 U2 9 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 7 BP 730 EP 755 PG 26 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 700UU UT WOS:000285770600013 PM 21152115 ER PT J AU Jia, R Li, CL Mccoy, JP Deng, CX Zheng, ZM AF Jia, Rong Li, Cuiling McCoy, J. Philip Deng, Chu-Xia Zheng, Zhi-Ming TI SRp20 is a proto-oncogene critical for cell proliferation and tumor induction and maintenance SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE Cancer; splicing factors; SFRS3; SRp20; G2/M arrest; cell transformation; tumor induction ID SR SPLICING FACTORS; POLO-LIKE KINASES; MESSENGER-RNA; TRANSCRIPTION FACTOR; GENE-EXPRESSION; BREAST-CANCER; MITOTIC PROGRESSION; OVARIAN-CANCER; FOXM1; PROTEIN AB Tumor cells display a different profile of gene expression than their normal counterparts. Perturbations in the levels of cellular splicing factors can alter gene expression, potentially leading to tumorigenesis. We found that splicing factor SRp20 (SFRS3) is highly expressed in cancers. SRp20 regulated the expression of Forkhead box transcription factor M1 (FoxM1) and two of its transcriptional targets, PLK1 and Cdc25B, and controlled cell cycl e progression and proliferation. Cancer cells with RNAi-mediated reduction of SRp20 expression exhibited G2/M arrest, growth retardation, and apoptosis. Increased SRp20 expression in rodent fibroblasts promoted immortal cell growth and transformation. More importantly, we found that SRp20 promoted tumor induction and the maintenance of tumor growth in nude mice and rendered immortal rodent fibroblasts tumorigenic. Collectively, these results suggest that increased SRp20 expression in tumor cells is a critical step for tumor initiation, progression, and maintenance. C1 [Jia, Rong; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Jia, Rong] Wuhan Univ, Sch Stomatol, Wuhan 430072, Hubei, Peoples R China. [Jia, Rong] Wuhan Univ, Hosp Stomatol, Wuhan 430072, Hubei, Peoples R China. [Li, Cuiling; Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, 10 Ctr Dr,Rm 6N106, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov RI deng, chuxia/N-6713-2016 FU Center for Cancer Research, NCI, NIH FX This research was supported by the Intramural Research Program of the Center for Cancer Research, NCI, NIH. We thank Javier Caceres and Tom Misteli for providing T7-SRp20 expression vector, Robert Yarchoan, Douglas Lowy, and Adrian Krainer for their critical comments and encouragement in the course of this study and for their critical reading of the manuscript; Curtis Harris and Izumi Horikawa for their critical reading of the manuscript; and Calvin Chan for his initial analysis of the Oncomine database. NR 63 TC 64 Z9 67 U1 1 U2 7 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2010 VL 6 IS 7 BP 806 EP 826 PG 21 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 700UU UT WOS:000285770600019 PM 21179588 ER PT J AU Martinez, JG Carroll, RJ Muller, S Sampson, JN Chatterjee, N AF Martinez, Josue G. Carroll, Raymond J. Muller, Samuel Sampson, Joshua N. Chatterjee, Nilanjan TI A Note on the Effect on Power of Score Tests via Dimension Reduction by Penalized Regression under the Null SO INTERNATIONAL JOURNAL OF BIOSTATISTICS LA English DT Article DE Adaptive Lasso; gene-environment interactions; Lasso; model selection; oracle estimation; score tests ID VARIABLE SELECTION; ORACLE PROPERTIES; ELASTIC-NET; LASSO AB We consider the problem of score testing for certain low dimensional parameters of interest in a model that could include finite but high dimensional secondary covariates and associated nuisance parameters. We investigate the possibility of the potential gain in power by reducing the dimensionality of the secondary variables via oracle estimators such as the Adaptive Lasso. As an application, we use a recently developed framework for score tests of association of a disease outcome with an exposure of interest in the presence of a possible interaction of the exposure with other co-factors of the model. We derive the local power of such tests and show that if the primary and secondary predictors are independent, then having an oracle estimator does not improve the local power of the score test. Conversely, if they are dependent, there is the potential for power gain. Simulations are used to validate the theoretical results and explore the extent of correlation needed between the primary and secondary covariates to observe an improvement of the power of the test by using the oracle estimator. Our conclusions are likely to hold more generally beyond the model of interactions considered here. C1 [Martinez, Josue G.; Carroll, Raymond J.] Texas A&M Univ, College Stn, TX 77843 USA. [Muller, Samuel] Univ Sydney, Sydney, NSW 2006, Australia. [Sampson, Joshua N.; Chatterjee, Nilanjan] NCI, Bethesda, MD 20892 USA. RP Martinez, JG (reprint author), Texas A&M Univ, College Stn, TX 77843 USA. RI Mueller, Samuel/D-4850-2009 OI Mueller, Samuel/0000-0002-3087-8127 FU National Cancer Institute [CA90301, R37-CA057030]; National Heart Lung and Blood Institute (NHLBI) FX Martinez was supported by a Postdoctoral Training grant from the National Cancer Institute (CA90301). Carroll's research was supported by a grant from the National Cancer Institute (R37-CA057030. Chatterjee's research was supported by a Gene-Environment Initiative (GEI) grant from the National Heart Lung and Blood Institute (NHLBI) and by the Intramural research program of the National Cancer Institute. This paper benefited from the constructive comments of two referees and an associate editor. NR 11 TC 3 Z9 3 U1 0 U2 1 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1557-4679 J9 INT J BIOSTAT JI Int. J. Biostat. PY 2010 VL 6 IS 1 AR 12 DI 10.2202/1557-4679.1231 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 858HV UT WOS:000297787600003 ER PT J AU Jiang, LY Abati, AD Wilson, W Stetler-Stevenson, M Yuan, C AF Jiang, Liuyan Abati, Andrea D. Wilson, Wyndham Stetler-Stevenson, Maryalice Yuan, Constance TI Persistent non-neoplastic gamma delta-T cells in cerebrospinal fluid of a patient with hepatosplenic (gamma delta) T cell lymphoma: a case report with 6 years of flow cytometry follow-up SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Article DE Gamma-delta T cells; hepatosplenic T cell lymphoma; cerebrospinal fluid; flow cytometry; T-cell gene rearrangement ID CENTRAL-NERVOUS-SYSTEM; PERIPHERAL-BLOOD; CLINICOPATHOLOGICAL ENTITY; BONE-MARROW; LYMPHOCYTES; CHEMOTHERAPY; REPERTOIRE; DISEASE AB Hepatosplenic (gamma delta) T-cell lymphoma (HSTCL) is an uncommon T-cell lymphoma with an aggressive clinical course and poor prognosis. Bone marrow and peripheral blood are frequently involved, with central nervous system involvement less common. We describe a case of a 31-year old man diagnosed with gamma delta HSTCL in 2003, successfully treated with chemotherapy and allogeneic stem cell transplantation, and followed from 2003 to present. Four-color flow cytometry (FC) was performed on a BD FACSCalibur and data analyzed with CellQuest Pro and FCS Express software. For cerebrospinal fluid (CSF), all cells were acquired due to limited material. Cytological correlation was available on all specimens. Molecular studies for T-cell gene rearrangement were non-contributory. By FC, the diagnostic HSTCL immunophenotype was CD3 (+), CD7 (+), CD2 (+), CD5 (-), CD4 (-), CD8 (-), TCR gamma delta (+). Subsequent CSF FC analysis revealed a distinct population of gamma delta T-cells in all specimens, ranging from <1% to 13% of lymphocytes. Consistently, the gamma delta T-cells exhibited a different immunophenotypic profile from the reported diagnostic immunophenotype; they expressed CD5, and exhibited a heterogeneous pattern of CD8 expression. Comparison to in-house cases from patients with hairy cell leukemia and concomitant increases in non-neoplastic gamma delta T-cells was performed. The persistent gamma delta T-cells from the CSF of the patient with HSTCL were immunophenotypically consistent with non-neoplastic gamma delta T-cells. We describe an unusual case of persistent gamma delta T-cells in the CSF of a patient during 6 years of flow cytometric follow-up after treatment for gamma delta HSTCL. By cytology, non-neoplastic and malignant gamma delta T-cells are often difficult to distinguish. FC analysis helps to make this distinction, even with a limited panel. By FC, the gamma delta-T cells in the CSF of this patient are immunophenotypically consistent with non-neoplastic gamma delta T-cells. Remarkably, this finding is underscored by the patient's unusual clinical picture; he remains well and disease free. C1 [Stetler-Stevenson, Maryalice; Yuan, Constance] NCI, Pathol Lab, Flow Cytometry Unit, NIH, Bethesda, MD 20892 USA. [Jiang, Liuyan] NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. [Abati, Andrea D.] NCI, Pathol Lab, Cytol Sect, NIH, Bethesda, MD 20892 USA. [Wilson, Wyndham] NCI, Pathol Lab, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Yuan, C (reprint author), NCI, Pathol Lab, Flow Cytometry Unit, NIH, Bldg 10, Bethesda, MD 20892 USA. EM yuanc@mail.nih.gov NR 26 TC 1 Z9 1 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2010 VL 3 IS 1 BP 110 EP 116 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 802JG UT WOS:000293505400011 ER PT J AU Gaiser, T Haedicke, W Becker, MR AF Gaiser, Timo Haedicke, Wolfgang Becker, Maria R. TI A rare pediatric case of a thymic cytotoxic and lymphoblastic T/NK cell lymphoma SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Article DE lymphoblastic lymphomas; T/NK cell lymphoma; pediatric lymphoma ID POLYMERASE CHAIN-REACTION; ACUTE-LEUKEMIA; T-CELL; GENE REARRANGEMENT; NEOPLASMS; CLASSIFICATION AB Attempts to establish a concise classification of lymphoblastic lymphomas (LBLs) have gained momentum in recent years, mainly due to the expanding possibilities of immunohistochemical and genetic characterization of different disease entities. Thus, cases of immature lymphoid malignancies with unusual immunopathological features have been reported during the last years, suggesting the need for new LBL classification concepts. To further characterize and demonstrate the extended spectrum of LBL, we present an unusual pediatric case of LBL that could not be categorized into one of the subgroups and exhibited a benign course after surgical treatment and subsequent chemotherapy. A mediastinal tumor of a 6-year-old Caucasian boy was examined by clinical staging, light microscopy, immunohistochemistry and PCR assays. The tumor cells reacted with TdT and had a positive cytoplasmic immunoreactivity for CD3. Further T-aand NK-cell markers CD1a, CD4, CD8, CD10, and CD56 reacted positively, but CD57, CD16 and CD 30 (Ber H2) were all negative. CD34 as a marker for bipotential B/T-precursors was also positive. B cell markers (CD20, CD22, Cd79a and IgM) were all negative. No clonal B cell Ig or T cell gamma chain rearrangements were detectable. Epstein Barr virus and other Herpes Virus DNA were not detected using a sensitive PCR assay. The applied chemotherapy was tolerated well and a complete remission of the tumor was achieved (observation period three years after the initial diagnosis). Localization, morphology, and the expressions markers made the tumor a typical member of the LBL group. However, our case represents a rare pediatric lymphoma derived from a thymic precursor committed to T/NK-cell differentiation and a favourable outcome after chemotherapy. C1 [Gaiser, Timo] NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA. [Haedicke, Wolfgang] IFP Spandau, Inst Pathol, Berlin, Germany. [Becker, Maria R.] Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany. RP Gaiser, T (reprint author), NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA. EM timo_gaiser@web.de FU German Cancer Aid; NIH FX We thank Irina Berger, M. D. for her contribution. T. G. was supported by a fellowship within the postdoctorate program of the German Cancer Aid. M. R. B. received a NIH grant. NR 26 TC 0 Z9 0 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2010 VL 3 IS 4 BP 437 EP 442 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 802JS UT WOS:000293506900010 PM 20490334 ER PT J AU Cha, HJ Philp, D Lee, SH Moon, HS Kleinman, HK Nakamura, T AF Cha, Hee-Jae Philp, Deborah Lee, Soo-Hyun Moon, Hye-Sung Kleinman, Hynda K. Nakamura, Takashi TI Over-expression of thymosin beta 4 promotes abnormal tooth development and stimulation of hair growth SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE thymosin beta 4; transgenic mice; hair growth; tooth development; laminin-5 ID ACTIN-SEQUESTERING PEPTIDE; GENE; BETA(4); CELLS; SKIN; BETA-1-INTEGRIN; PROLIFERATION; ANGIOGENESIS; AMELOBLASTS; METASTASIS AB Thymosin beta 4 has multi-functional roles in cell physiology. It accelerates wound healing, hair growth and angiogenesis, and increases laminin-5 expression in corneal epithelium. Furthermore, thymosin beta 4 stimulates tumor growth and metastasis by induction of cell migration and vascular endothelial growth factor-mediated angiogenesis. Using a construct on the skin-specific keratin-5 promoter, we have developed thymosin beta 4 over-expressing transgenic mice to further study its functional roles. Thymosin beta 4 in adult skin and in embryonic stages of the transgenic mouse was analyzed by both Western blot and immunohistochemistry. The overexpression of thymosin beta 4 was observed especially around hair follicles and in the teeth in the transgenic mice. We examined the phenotype of the thymosin beta 4 over-expressing mice. Hair growth was accelerated. In addition, the transgenic mice had abnormally-shaped white teeth and dull incisors. We found that the expression of laminin-5 was up-regulated in the skin of the transgenic mice. We conclude that thymosin beta 4 has an important physiological role in hair growth and in tooth development. C1 [Cha, Hee-Jae] Kosin Univ, Dept Parasitol & Genet, Coll Med, Pusan 602703, South Korea. [Philp, Deborah; Kleinman, Hynda K.; Nakamura, Takashi] Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. [Lee, Soo-Hyun] Seoul Natl Univ, Dept Pharmaceut, Coll Pharm, Seoul, South Korea. [Moon, Hye-Sung] Ewha Womans Univ, Sch Med, Dept Obstet & Gynecol, Seoul, South Korea. RP Cha, HJ (reprint author), Kosin Univ, Dept Parasitol & Genet, Coll Med, 34 Annam Dong, Pusan 602703, South Korea. EM hcha@kosin.ac.kr RI Nakamura, Takashi/P-7796-2016 OI Nakamura, Takashi/0000-0001-9904-1037 FU Korea government (MEST) [KRF-20090066740]; Kosin University College of Medicine FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (KRF-20090066740) and a grant from the Kosin University College of Medicine (2007). NR 29 TC 25 Z9 29 U1 0 U2 2 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2010 VL 54 IS 1 BP 135 EP 140 DI 10.1387/ijdb.082735hc PG 6 WC Developmental Biology SC Developmental Biology GA 562RK UT WOS:000275071300014 PM 20013654 ER PT J AU Swanhart, LM Takahashi, N Jackson, RL Gibson, GA Watkins, SC Dawid, IB Hukriede, NA AF Swanhart, Lisa M. Takahashi, Nobuhiro Jackson, Rachel L. Gibson, Gregory A. Watkins, Simon C. Dawid, Igor B. Hukriede, Neil A. TI Characterization of an lhx1a transgenic reporter in zebrafish SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE lhx1a; transgene; zebrafish; kidney; gastrulation ID ORGANIZER; LIM1; GENE; MESODERM; REQUIREMENT; EXPRESSION; ACTIVIN; SIGNALS; PATTERN; EMBRYOS AB The LIM-domain containing transcription factor, Lhx1, is involved in the regulation of early gastrulation cell movements, kidney organogenesis and other processes in vertebrate model organisms. To follow the expression of this gene in live embryos, we created transgenic zebrafish expressing enhanced green fluorescent protein (EGFP) under the control of lhx1a regulatory regions. Tg(lhx1a:EGFP)(pt303) recapitulates the expression of endogenous lhx1a beginning at early gastrula stages through 72 hours of development with only few exceptions. In addition, over-expression of the Nodal ligand, ndr1, results in the concomitant expansion of the transgene and endogenous lhx1a expression. Treatment of Tg(lhx1a:EGFP)(pt303) embryos with the small molecule SB-431542, an inhibitor of Nodal signaling, results in the loss of both transgene and endogenous lhx1a expression. These experiments suggest that Tg(lhx1a:EGFP)(pt303) is regulated in a manner similar to endogenous lhx1a. Therefore, this reporter can be utilized not only for monitoring lhx1a expression, but also for numerous applications, including chemical genetics screening. C1 [Swanhart, Lisa M.; Jackson, Rachel L.; Hukriede, Neil A.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15213 USA. [Takahashi, Nobuhiro; Dawid, Igor B.] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Gibson, Gregory A.; Watkins, Simon C.] Univ Pittsburgh, Ctr Biol Imaging, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Hukriede, Neil A.] Univ Pittsburgh, Drug Discovery Inst, Pittsburgh, PA USA. RP Hukriede, NA (reprint author), Univ Pittsburgh, Dept Microbiol & Mol Genet, 3501 5th Ave,5601 BST3, Pittsburgh, PA 15213 USA. EM hukriede@pitt.edu FU National Institutes of Health, USA [R01DK069403, R01HD053287, P30DK079307]; NICHD FX We would like to thank Lance Davidson for help with con focal microscopy; Dave Grainy and Gretchen Blasko for fish care; Wade Znosko for critical reading of the manuscript; David Kozlowski for identification of anatomical structures; Nathan Bahaty for the mCherry expression plasmid; Mike Rebagliati for the ndr1 expression plasmid and Michael Tsang for suggestions and advice. This work has been funded by the National Institutes of Health, USA: R01DK069403, R01HD053287, P30DK079307 and the NICHD Intramural Program. NR 21 TC 13 Z9 13 U1 0 U2 3 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2010 VL 54 IS 4 BP 731 EP 736 DI 10.1387/ijdb.092969ls PG 6 WC Developmental Biology SC Developmental Biology GA 589EH UT WOS:000277128600021 PM 20209443 ER PT J AU De Wever, O Hendrix, A De Boeck, A Westbroek, W Braems, G Emami, S Sabbah, M Gespach, C Bracke, M AF De Wever, Olivier Hendrix, An De Boeck, Astrid Westbroek, Wendy Braems, Geert Emami, Shahin Sabbah, Michele Gespach, Christian Bracke, Marc TI Modeling and quantification of cancer cell invasion through collagen type I matrices SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE invasion; collagen; stroma; 3D matrices; ecosystem ID BREAST-CANCER; SIGNALING PATHWAYS; GROWTH-FACTOR; TUMOR-CELLS; N-CADHERIN; TGF-BETA; VITRO; DIFFERENTIATION; GENE; MICROENVIRONMENT AB Tumor invasion is the outcome of a complex interplay between cancer cells and the stromal environment. Considering the contribution of the stromal environment, we developed a membrane-free single-cell and spheroid based complementary model to study cancer invasion through native collagen type-I matrices. Cell morphology is preserved during the assays allowing real time monitoring of invasion-induced changes in cell structure and F-actin organization. Combining these models with computerized quantification permits the calculation of highly reproducible and operator-independent data. These assays are versatile in the use of fluorescent probes and have a flexible kinetic endpoint. Once the optimal experimental conditions are empirically determined, the collagen type-I invasion assays can be used for preclinical validation of small-molecule inhibitors targeting invasion. Initiation and monitoring of the single-cell and spheroid invasion model can be achieved in 8 h (over 3 days) and in 14 h (over 8 days) respectively. C1 [De Wever, Olivier; De Boeck, Astrid; Bracke, Marc] Ghent Univ Hosp, Lab Expt Canc Res, Dept Radiotherapy & Nucl Med, B-9000 Ghent, Belgium. [Hendrix, An] Ghent Univ Hosp, Dept Med Oncol, B-9000 Ghent, Belgium. [Braems, Geert] Ghent Univ Hosp, Dept Gynaecol, B-9000 Ghent, Belgium. [Westbroek, Wendy] NHGRI, NIH, Bethesda, MD 20892 USA. [Emami, Shahin; Sabbah, Michele; Gespach, Christian] INSERM, U673, Paris, France. [Emami, Shahin; Gespach, Christian] INSERM, U938, Paris, France. [Emami, Shahin; Gespach, Christian] Univ Paris 06, Fac Med, Paris, France. RP De Wever, O (reprint author), Ghent Univ Hosp, Lab Expt Canc Res, Dept Radiotherapy & Nucl Med, De Pintelaan 185, B-9000 Ghent, Belgium. EM olivier.dewever@UGent.be RI de wever, olivier/J-3094-2013 OI de wever, olivier/0000-0002-5453-760X FU Fund for Scientific Research-Flanders (Brussels, Belgium) [FWOAL455]; INSERM; ARC; Flemish community and France [1.2007.03, T2009.14]; EACR; Fund for Scientific Research-Flanders; National Human Genome Research Institute FX M. Mareel is gratefully acknowledged for stimulating discussions. We thank Georges De Bruyne for excellent technical assistance. This work was funded by Fund for Scientific Research-Flanders (Kom op Tegen Kanker-VLK: FWOAL455) (Brussels, Belgium), INSERM, ARC and the Scientific Exchange Program between the Flemish community and France (Grant 1.2007.03; T2009.14). O. De Wever was supported by an EACR travelfellowship, and a post-doctoral grant from Fund for Scientific Research-Flanders. W. Westbroek was supported by the Intramural Research Program of the National Human Genome Research Institute. NR 33 TC 46 Z9 46 U1 5 U2 23 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2010 VL 54 IS 5 BP 887 EP 896 DI 10.1387/ijdb.092948ow PG 10 WC Developmental Biology SC Developmental Biology GA 616CB UT WOS:000279184400013 PM 19757378 ER PT J AU Kam, RKT Chen, YL Chan, SO Chan, WY Dawid, IB Zhao, H AF Kam, Richard K. T. Chen, Yonglong Chan, Sun-On Chan, Wood-Yee Dawid, Igor B. Zhao, Hui TI Developmental expression of Xenopus short-chain dehydrogenase/reductase 3 SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE dhrs3; retinoic acid; Xenopus ID EMBRYONIC RETINOIC ACID; CENTRAL-NERVOUS-SYSTEM; SIGNAL PEPTIDES AB During early embryonic development, the retinoic acid signaling pathway coordinates with other signaling pathways to regulate body axis patterning and organogenesis. The production of retinoic acid requires two enzymatic reactions, the first of which is the oxidization of vitamin A (all-trans-retinol) to all-trans -retinal, mediated in part by the short-chain dehydrogenase/reductase. Through DNA microarrays, we have identified a gene in Xenopus laevis which shares a high sequence similarity to human short-chain dehydrogenase/reductase member 3. We therefore annotated the gene Xenopus short-chain dehydrogenase/reductase 3 (dhrs3). Expression of dhrs3 was detected by whole mount in situ hybridization in the dorsal blastopore lip and axial mesoderm region in gastrula embryos. During neurulation, dhrs3 transcripts were found in the notochord and neural ectoderm. Strong expression of dhrs3 was mainly detected in the brain, spinal cord and pronephros region in tailbud and tadpole stages. Temporal expression tested by RT-PCR indicated that dhrs3 was activated at the onset of gastrulation, and remained highly expressed at later stages of embryonic development. The distinct and highly regulated spatial and temporal expression of dhrs3 highlights the complexity of retinoic acid regulation. C1 [Kam, Richard K. T.; Chan, Sun-On; Chan, Wood-Yee; Zhao, Hui] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Chen, Yonglong] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Key Lab Regenerat Biol, Guangzhou, Guangdong, Peoples R China. [Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD USA. RP Zhao, H (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. EM zhaohui@cuhk.edu.hk RI Zhao, Hui/B-8429-2016 FU Department of Anatomy; Chinese University of Hong Kong, Hong Kong; National Institute of Child Health and Human Development, National Institutes of Health, USA FX We thank WONG Chi Bun Thomas for technical advices on sectioning. This work was supported by the one-line budget of Department of Anatomy, The Chinese University of Hong Kong, Hong Kong to HZ., and the Intramural Research Program of National Institute of Child Health and Human Development, National Institutes of Health, USA to I.D. NR 24 TC 7 Z9 7 U1 0 U2 5 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2010 VL 54 IS 8-9 BP 1355 EP 1360 DI 10.1387/ijdb.092984rk PG 6 WC Developmental Biology SC Developmental Biology GA 687BA UT WOS:000284747500017 PM 20563993 ER PT J AU Simons-Morton, B Pickett, W Boyce, W ter Bogt, TFM Vollebergh, W AF Simons-Morton, Bruce Pickett, William Boyce, Will ter Bogt, Tom F. M. Vollebergh, Wilma TI Cross-national comparison of adolescent drinking and cannabis use in the United States, Canada, and the Netherlands SO INTERNATIONAL JOURNAL OF DRUG POLICY LA English DT Article DE Alcohol; Cannabis; Policy; International; Adolescent substance use ID MENTAL-HEALTH; MARIJUANA USE; ALCOHOL; POLICY; COUNTRIES; AMERICAN; INJURY; ONSET; RISK AB Background: This research examined the prevalence of drinking and cannabis use among adolescents in the United States, Canada, and the Netherlands, countries with substantially different laws and policies relating to these substances. Methods: Laws regarding drinking and cannabis use were rated for each country. Substance use prevalence data among 10th graders from the Health Behaviour in School-Aged Children Survey conducted in each country in 2005-2006 were examined. Results: Laws regarding alcohol and cannabis were found to be strictest in the United States, somewhat less strict in Canada, and least strict in the Netherlands. On most measures of drinking, rates were lower in the United States than in Canada or the Netherlands. With United States as the referent, relative risks (RR) for monthly drinking were 1.30 (1.11-1.53) for Canadian boys and 1.55 (1.31-1.83) for girls, and 2.0 (1.73-2.31) for Dutch boys and 1.92 (1.62-2.27) for Dutch girls. Drunkenness was also higher among Canadian boys and girls and Dutch boys. However, rates of cannabis use did not differ between the countries, except that Dutch girls were less likely to use cannabis in the past year (RR = .67; .46-96). Conclusions: The lower prevalence of adolescent drinking and drunkenness (except among Dutch girls) in the United States is consistent with the contention that strict drinking policies may limit drinking among 10th graders. However, the finding that cannabis use rates did not differ across countries is not consistent with the contention that prohibition-oriented policies deter use or that liberal cannabis policies are associated with elevated adolescent use. Based on these findings, the case for strict laws and policies is considerably weaker for cannabis than for alcohol. (C) 2009 Elsevier B.V. All rights reserved. C1 [Simons-Morton, Bruce] NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Eunice Shriver Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. [Pickett, William; Boyce, Will] Queens Univ, Kingston Gen Hosp, Dept Epidemiol & Community Hlth, Kingston, ON K7M 2V7, Canada. [ter Bogt, Tom F. M.] Queens Univ, Evaluat Grp, Fac Educ, Social Program, Kingston, ON K7L 3N6, Canada. [Vollebergh, Wilma] Univ Utrecht, Dept Interdisciplinary Social Sci, NL-3508 TC Utrecht, Netherlands. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Eunice Shriver Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. EM Mortonb@mail.nih.gov; Pickettw@post.queensu.ca; t.f.m.terbogt@uu.nl; w.a.m.vollebergh@uu.nl RI Vollebergh, Wilma/C-2323-2012; OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [Z01 HD002525-13]; NICHD NIH HHS [N01-HD-5-3401] NR 41 TC 28 Z9 28 U1 4 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0955-3959 J9 INT J DRUG POLICY JI Int. J. Drug Policy PD JAN PY 2010 VL 21 IS 1 BP 64 EP 69 DI 10.1016/j.drugpo.2009.02.003 PG 6 WC Substance Abuse SC Substance Abuse GA 547RX UT WOS:000273908000010 PM 19303761 ER PT J AU Karami, S Brennan, P Navratilova, M Mates, D Zaridze, D Janout, V Kollarova, H Bencko, V Matveev, V Szesznia-Dabrowska, N Holcatova, I Yeager, M Chanock, S Rothman, N Boffetta, P Chow, WH Moore, LE AF Karami, S. Brennan, P. Navratilova, M. Mates, D. Zaridze, D. Janout, V. Kollarova, H. Bencko, V. Matveev, V. Szesznia-Dabrowska, N. Holcatova, I. Yeager, M. Chanock, S. Rothman, N. Boffetta, P. Chow, W-H. Moore, L. E. TI Vitamin D Pathway Genes, Diet, and Risk of Renal Cell Carcinoma SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Article ID D-RECEPTOR GENE; PROSTATE-CANCER; CENTRAL-EUROPE; KIDNEY CANCER; ULTRAVIOLET-RADIATION; COLORECTAL-CANCER; FISH CONSUMPTION; SUN EXPOSURE; POLYMORPHISMS; SUSCEPTIBILITY AB Mediated by binding to the high-affinity vitamin D receptor (VDR), vitamin D forms a heterodimer complex with the retinoid-X-receptor (RXR). Variation in both genes has been shown to modify renal cell carcinoma (RCC) risk. Therefore, we investigated whether VDR and RXRA polymorphisms modify associations between RCC risk and frequency of dietary intake of vitamin D and calcium rich foods, and occupational ultraviolet exposure among 777 RCC case and 1035 controls from Central and Eastern Europe. A positive association was observed in this population between increasing dietary intake frequency of yogurt, while an inverse association was observed with egg intake frequency. RXRA polymorphisms, located 3' of the coding sequence, modified associations between specific vitamin D rich foods and RCC risk, while RXRA polymorphisms, located in introns 1 and 4, modified associations with specific calcium rich foods. Results suggest that variants in the RXRA gene modified the associations observed between RCC risk and calcium and vitamin D intake. C1 [Karami, S.; Rothman, N.; Chow, W-H.; Moore, L. E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Brennan, P.; Boffetta, P.] Int Agcy Res Canc, F-69372 Lyon, France. [Navratilova, M.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Mates, D.] Inst Publ Hlth, Bucharest, Romania. [Zaridze, D.; Matveev, V.] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Janout, V.; Kollarova, H.] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Bencko, V.; Holcatova, I.] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, CR-11636 Prague 1, Czech Republic. [Szesznia-Dabrowska, N.] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Yeager, M.; Chanock, S.] Bethseda Natl Canc Inst, Core Genotyping Facil, Adv Technol Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM karamis@mail.nih.gov RI Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; OI mates, dana/0000-0002-6219-9807 NR 44 TC 12 Z9 12 U1 1 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2010 AR 879362 DI 10.1155/2010/879362 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 689PA UT WOS:000284939100001 ER PT J AU Youngstrom, E LaKind, JS Kenworthy, L Lipkin, PH Goodman, M Squibb, K Mattison, DR Anthony, BJ Anthony, LG AF Youngstrom, Eric LaKind, Judy S. Kenworthy, Lauren Lipkin, Paul H. Goodman, Michael Squibb, Katherine Mattison, Donald R. Anthony, Bruno J. Anthony, Laura Gutermuth TI Advancing the Selection of Neurodevelopmental Measures in Epidemiological Studies of Environmental Chemical Exposure and Health Effects SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE neurodevelopmental measures; neurodevelopment; polychlorinated biphenyls; PCBs; children's health; domain; psychometrics; developmental epidemiology ID IQ GAINS; VALIDITY AB With research suggesting increasing incidence of pediatric neurodevelopmental disorders, questions regarding etiology continue to be raised. Neurodevelopmental function tests have been used in epidemiology studies to evaluate relationships between environmental chemical exposures and neurodevelopmental deficits. Limitations of currently used tests and difficulties with their interpretation have been described, but a comprehensive critical examination of tests commonly used in studies of environmental chemicals and pediatric neurodevelopmental disorders has not been conducted. We provide here a listing and critical evaluation of commonly used neurodevelopmental tests in studies exploring effects from chemical exposures and recommend measures that are not often used, but should be considered. We also discuss important considerations in selecting appropriate tests and provide a case study by reviewing the literature on polychlorinated biphenyls. C1 [LaKind, Judy S.] LaKind Associates LLC, Catonsville, MD 21228 USA. [Youngstrom, Eric] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Youngstrom, Eric] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [LaKind, Judy S.] Univ Maryland, Dept Epidemiol & Prevent Med, Sch Med, Baltimore, MD 21202 USA. [LaKind, Judy S.] Penn State Coll Med, Dept Pediat, Hershey, PA 17033 USA. [Kenworthy, Lauren; Anthony, Laura Gutermuth] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders,Dept Pediat, Rockville, MD 20850 USA. [Kenworthy, Lauren; Anthony, Laura Gutermuth] George Washington Univ, Sch Med, Ctr Autism Spectrum Disorders, Childrens Natl Med Ctr,Dept Neurol, Rockville, MD 20850 USA. [Lipkin, Paul H.] Johns Hopkins Univ, Sch Med, Ctr Dev & Learning, Kennedy Krieger Inst,Dept Pediat, Baltimore, MD 21205 USA. [Goodman, Michael] Emory Univ, Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Squibb, Katherine] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Anthony, Bruno J.] Georgetown Univ, Dept Pediat, Ctr Child & Human Dev, Washington, DC 20007 USA. [Kenworthy, Lauren; Anthony, Laura Gutermuth] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders,Dept Psychiat, Rockville, MD 20850 USA. RP LaKind, JS (reprint author), LaKind Associates LLC, 106 Oakdale Ave, Catonsville, MD 21228 USA. EM Eric.Youngstrom@unc.edu; lakindassoc@comcast.net; lkenwort@cnmc.org; lipkin@kennedykrieger.org; mgoodm2@sph.emory.edu; Ksquibb@umaryland.edu; mattisod@mail.nih.gov; bja28@georgetown.edu; LAnthony@cnmc.org RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; Lipkin, Paul/0000-0002-9043-2581 FU Cefic-Long-range Research Initiative FX This research was supported by a grant from Cefic-Long-range Research Initiative (LRI). Cefic-LRI was not involved in the design, collection, management, analysis, or interpretation of the data; or in the preparation or approval of the manuscript. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the views of Cefic-LRI or the National Institutes of Health. The authors gratefully acknowledge the recommendations on existing and recommended alternative measures (Table 1) from panel members at a neurodevelopmental function testing Workshop held in Baltimore, Maryland, USA in June 2009. In addition to the authors of this paper, the panel consisted of: Alice S. Carter, University of Massachusetts, Boston, Yale University, Boston University School of Medicine; Christa Einspieler, Medical University of Graz; Thomas Frazier II, Cleveland Clinic Children's Hospital; Marsha Gerdes, The Children's Hospital of Philadelphia; Mijna Hadders-Algra, University Medical Center Groningen; Walter E. Kaufmann, The Kennedy Krieger Institute, The Johns Hopkins University School of Medicine; E. Mark Mahone, The Kennedy Krieger Institute, The Johns Hopkins University School of Medicine; Susan L. Makris, US Environmental Protection Agency; Poul Thorsen, Emory University Rollins School of Public Health, University of Aarhus, Denmark. NR 80 TC 6 Z9 6 U1 0 U2 1 PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD JAN PY 2010 VL 7 IS 1 BP 229 EP 268 DI 10.3390/ijerph7010229 PG 40 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 548WR UT WOS:000274000900016 PM 20195443 ER PT J AU Gasselhuber, A Dreher, MR Negussie, A Wood, BJ Rattay, F Haemmerich, D AF Gasselhuber, Astrid Dreher, Matthew R. Negussie, Ayele Wood, Bradford J. Rattay, Frank Haemmerich, Dieter TI Mathematical spatio-temporal model of drug delivery from low temperature sensitive liposomes during radiofrequency tumour ablation SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE radiofrequency ablation; tumor ablation; liposomes; LTSL; drug delivery; pharmacokinetics; modeling ID MICROVASCULAR PERMEABILITY; THERMAL-CONDUCTIVITY; CONTINUOUS-INFUSION; LOCAL HYPERTHERMIA; INCREASED NECROSIS; CIRCULATION TIME; BOLUS INJECTION; BREAST-CANCER; DOXORUBICIN; TISSUE AB Purpose: Studies have demonstrated a synergistic effect between hyperthermia and chemotherapy, and clinical trials in image-guided drug delivery combine high-temperature thermal therapy (ablation) with chemotherapy agents released in the heating zone via low temperature sensitive liposomes (LTSL). The complex interplay between heat-based cancer treatments such as thermal ablation and chemotherapy may require computational models to identify the relationship between heat exposure and pharmacokinetics in order to optimise drug delivery. Materials and methods: Spatio-temporal data on tissue temperature and perfusion from heat-transfer models of radiofrequency ablation were used as input data. A spatio-temporal multi-compartmental pharmacokinetic model was built to describe the release of doxorubicin (DOX) from LTSL into the tumour plasma space, and subsequent transport into the extracellular space, and the cells. Systemic plasma and tissue compartments were also included. We compared standard chemotherapy (free-DOX) to LTSL-DOX administered as bolus at a dose of 0.7 mg/kg body weight. Results: Modelling LTSL-DOX treatment resulted in tumour tissue drug concentration of similar to 9.3 mu g/g with highest values within 1 cm outside the ablation zone boundary. Free-DOX treatment produced comparably uniform tissue drug concentrations of similar to 3.0 mu g/g. Administration of free-DOX resulted in a considerably higher peak level of drug concentration in the systemic plasma compartment (16.1 mu g/g) compared to LTSL-DOX (4.4 mu g/g). These results correlate well with a prior in vivo study. Conclusions: Combination of LTSL-DOX with thermal ablation allows localised drug delivery with higher tumour tissue concentrations than conventional chemotherapy. Our model may facilitate drug delivery optimisation via investigation of the interplays among liposome properties, tumour perfusion, and heating regimen. C1 [Gasselhuber, Astrid; Haemmerich, Dieter] Med Univ S Carolina, Div Pediat Cardiol, Charleston, SC 29425 USA. [Dreher, Matthew R.; Negussie, Ayele; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Gasselhuber, Astrid; Rattay, Frank] Vienna Univ Technol, Inst Anal & Sci Comp, A-1040 Vienna, Austria. [Haemmerich, Dieter] Clemson Univ, Dept Bioengn, Clemson, SC USA. RP Haemmerich, D (reprint author), Med Univ S Carolina, Div Pediat Cardiol, 165 Ashley Ave,MSC 915, Charleston, SC 29425 USA. EM haemmer@musc.edu RI Rattay, Frank/A-2231-2015; OI Rattay, Frank/0000-0002-2819-8827; Haemmerich, Dieter/0000-0003-1127-7024 FU National Institutes of Health Center for Interventional Oncology & National Institutes of Health; National Institutes of Health [R01 CA108869]; National Center for Research Resources [C06 RR018823] FX This work was supported in part by the National Institutes of Health Center for Interventional Oncology & National Institutes of Health Intramural Research Program. Part of this work was conducted in a facility constructed with support from the National Institutes of Health, Grant Number C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. In addition, this work was supported by National Institutes of Health grant Number R01 CA108869. NR 59 TC 39 Z9 40 U1 0 U2 23 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PY 2010 VL 26 IS 5 BP 499 EP 513 DI 10.3109/02656731003623590 PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 624FO UT WOS:000279802300009 PM 20377363 ER PT J AU Coelho, VD Bunbury, A Rangel, LB Giri, B Weeraratna, A Morin, PJ Bernier, M Taub, DD AF Coelho, Valeria de Mello Bunbury, Allyson Rangel, Leticia B. Giri, Banabihari Weeraratna, Ashani Morin, Patrice J. Bernier, Michel Taub, Dennis D. TI Fat-Storing Multilocular Cells Expressing CCR5 Increase in the Thymus with Advancing Age: Potential Role for CCR5 Ligands on the Differentiation and Migration of Preadipocytes SO INTERNATIONAL JOURNAL OF MEDICAL SCIENCES LA English DT Article DE thymus; aging; adipocyte; differentiation; chemokines; chemotaxis; involution; adipokines ID MESENCHYMAL STEM-CELLS; ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION; ADIPOGENESIS; INVOLUTION; ENDOCRINE; MICE; MICROENVIRONMENT; REGENERATION; INFLAMMATION AB Age-associated thymic involution is characterized by decreased thymopoiesis, adipocyte deposition and changes in the expression of various thymic microenvironmental factors. In this work, we characterized the distribution of fat-storing cells within the aging thymus. We found an increase of unilocular adipocytes, ERTR7(+) and CCR5(+) fat-storing multilocular cells in the thymic septa and parenchymal regions, thus suggesting that mesenchymal cells could be immigrating and differentiating in the aging thymus. We verified that the expression of CCR5 and its ligands, CCL3, CCL4 and CCL5, were increased in the thymus with age. Hypothesizing that the increased expression of chemokines and the CCR5 receptor may play a role in adipocyte recruitment and/or differentiation within the aging thymus, we examined the potential role for CCR5 signaling on adipocyte physiology using 3T3-L1 pre-adipocyte cell line. Increased expression of the adipocyte differentiation markers, PPAR gamma 2 and aP2 in 3T3-L1 cells was observed under treatment with CCR5 ligands. Moreover, 3T3-L1 cells demonstrated an ability to migrate in vitro in response to CCR5 ligands. We believe that the increased presence of fat-storing cells expressing CCR5 within the aging thymus strongly suggests that these cells may be an active component of the thymic stromal cell compartment in the physiology of thymic aging. Moreover, we found that adipocyte differentiation appear to be influenced by the proinflammatory chemokines, CCL3, CCL4 and CCL5. C1 [Taub, Dennis D.] NIA, Labs Immunol, Clin Immunol Sect, Intramural Res Program,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Coelho, Valeria de Mello] Univ Fed Rio de Janeiro, Inst Biomed Sci, BR-21941 Rio De Janeiro, Brazil. RP Taub, DD (reprint author), NIA, Labs Immunol, Clin Immunol Sect, Intramural Res Program,NIH,Biomed Res Ctr, 251 Bayview Blvd,Room 8C222, Baltimore, MD 21224 USA. EM TaubD@grc.nia.nih.gov OI Bernier, Michel/0000-0002-5948-368X FU National Institute on Aging, National Institutes of Health FX We thank Dr. Alan Sher and Andre Bafica from NIAID for kindly providing the aged CCR5-deficient mice for certain studies and Prof. Dr. Radovan Borojevic for valuable discussions on this work. This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 45 TC 2 Z9 3 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA J9 INT J MED SCI JI Int. J. Med. Sci. PY 2010 VL 7 IS 1 BP 1 EP 14 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 541HJ UT WOS:000273405600001 ER PT J AU Cherukuri, MK Mitchell, JB AF Cherukuri, Murali Krishna Mitchell, James B. TI Magnetic resonance imaging of tumor oxygen status in vivo SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Cherukuri, Murali Krishna; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PY 2010 VL 26 SU 1 MA 139 BP S14 EP S14 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 667OM UT WOS:000283203400040 ER PT J AU Stein, U Arlt, F Smith, J Sack, U Walther, W Fichtner, I Shoemaker, RH Schlag, PM AF Stein, Ulrike Arlt, Franziska Smith, Janice Sack, Ulrike Walther, Wolfgang Fichtner, Iduna Shoemaker, Robert H. Schlag, Peter M. TI The metastasis inducer S100A4: Cell signaling-based interventions for reduction of colon cancer metastasis SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Stein, Ulrike; Walther, Wolfgang] Charite, Expt & Clin Res Ctr, D-13353 Berlin, Germany. [Stein, Ulrike; Smith, Janice; Sack, Ulrike; Walther, Wolfgang; Fichtner, Iduna] Max Delbruck Ctr Mol Med, Berlin, Germany. [Arlt, Franziska] Charite, Robert Rossle Clin, D-13353 Berlin, Germany. [Shoemaker, Robert H.] NCI, Frederick, MD 21701 USA. [Schlag, Peter M.] Charite Comprehens Canc Ctr, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PY 2010 VL 26 SU 1 MA 237 BP S39 EP S39 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 667OM UT WOS:000283203400138 ER PT J AU Chuang, DM Wang, Z Chiu, CT Liu, G Leeds, P Leng, Y AF Chuang, D. -M. Wang, Z. Chiu, C-T. Liu, G. Leeds, P. Leng, Y. TI The mood stabilizer valproate induces protective effects in neurodegenerative and neuropsychiatric models through HDAC inhibition SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Chuang, D. -M.; Wang, Z.; Chiu, C-T.; Liu, G.; Leeds, P.; Leng, Y.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 8 EP 8 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100022 ER PT J AU Cannon, D Klaver, JM Peck, SA Carlson, PJ Ichise, M Drevets, WC AF Cannon, D. Klaver, J. M. Peck, S. A. Carlson, P. J. Ichise, M. Drevets, W. C. TI Abnormalities in the serotonergic system in panic disorder: Evidence from neuroimaging studies SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Cannon, D.] Natl Univ Ireland, Dept Psychiat, Galway, Ireland. [Klaver, J. M.; Peck, S. A.; Carlson, P. J.; Drevets, W. C.] Natl Inst Hlth, Bethesda, MD USA. [Ichise, M.] Columbia Univ, New York, NY 10027 USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 10 EP 10 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100028 ER PT J AU Zarate, C AF Zarate, C. TI Glutamatergic modulators and treatment biomarkers of response in bipolar disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Zarate, C.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 11 EP 11 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100031 ER PT J AU Manji, H Du, J Chen, G Zarate, CA AF Manji, H. Du, J. Chen, G. Zarate, C. A., Jr. TI Regulating AMPA/NMDA mediated synaptic plasticity in critical circuits for the development of novel, improved rapidly acting therapeutics SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Du, J.; Chen, G.; Zarate, C. A., Jr.] NIMH, NIH, Titusville, MD USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 12 EP 12 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100036 ER PT J AU Lovestone, S Thambisetty, M Kronenberg, D Hye, A Furney, S Simmons, A Guntert, A AddNeuroMed, C AF Lovestone, S. Thambisetty, M. Kronenberg, D. Hye, A. Furney, S. Simmons, A. Guntert, A. AddNeuroMed, C. TI Combinatorial, multimodal biomarkers from large variable datasets findings from the addneuromed study SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Lovestone, S.] Kings Coll London, Inst Psychiat, London, England. [Thambisetty, M.] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 17 EP 17 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100056 ER PT J AU Fox, MA Murphy, DL AF Fox, M. A. Murphy, D. L. TI Mouse models of genetic vulnerability to the serotonin syndrome: Behavioral, temperature and receptor signaling alterations SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Fox, M. A.; Murphy, D. L.] NIMH, NIH, LCS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 42 EP 42 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100145 ER PT J AU Martinowich, K Schloesser, RJ Lu, Y Greene, JS Greig, NH Manji, H Lu, B AF Martinowich, K. Schloesser, R. J. Lu, Y. Greene, J. S. Greig, N. H. Manji, H. Lu, B. TI Long-term depression as a mechanism for coping with acute stress: Role of p75NTR and cholinergic transmission SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Martinowich, K.; Schloesser, R. J.; Lu, Y.; Greene, J. S.; Greig, N. H.; Lu, B.] Natl Inst Hlth, Bethesda, MD USA. [Martinowich, K.; Schloesser, R. J.; Lu, Y.; Greene, J. S.; Greig, N. H.; Lu, B.] Natl Inst Hlth, Baltimore, MD USA. RI Lu, Bai/A-4018-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 45 EP 45 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100155 ER PT J AU Cannon, D Klaver, JM Peck, SA Carlson, PJ Ichise, M Drevets, WC AF Cannon, D. Klaver, J. M. Peck, S. A. Carlson, P. J. Ichise, M. Drevets, W. C. TI Abnormalities in the serotonergic system in panic disorder: Evidence from neuroimaging studies SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Cannon, D.] Natl Univ Ireland, Dept Psychiat, Galway, Ireland. [Klaver, J. M.; Peck, S. A.; Carlson, P. J.; Drevets, W. C.] Natl Inst Hlth, Bethesda, MD USA. [Ichise, M.] Columbia Univ, New York, NY 10027 USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 46 EP 46 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100160 ER PT J AU Arime, Y Hall, S Uhl, G Sora, I AF Arime, Y. Hall, S. Uhl, G. Sora, I. TI Prefrontal Norepinephrine Transporter Blockade Ameliorates Deficits of Prepulse Inhibition in Dopamine Transporter Knockout Mice via Cortico-subcortical Glutamate Projections SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Arime, Y.; Sora, I.] Tohoku Univ, Sendai, Miyagi 980, Japan. [Hall, S.; Uhl, G.] NIDA IRP, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 59 EP 59 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100209 ER PT J AU Su, TP Tsai, SY Hayashi, T AF Su, T. -P. Tsai, S. -Y. Hayashi, T. TI Hippocampal dendritic spine formation is controlled by the ER-mitochondrion-Rac.GTP pathway via a free radical-sensitive mechanism involving sigma-1 receptors SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 27th CINP Congress Meeting 2010 CY JUN 06-10, 2010 CL Hong Kong, PEOPLES R CHINA C1 [Su, T. -P.; Tsai, S. -Y.; Hayashi, T.] IRP NIDA NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PY 2010 VL 13 SU 1 BP 83 EP 83 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 643FN UT WOS:000281281100297 ER PT J AU Weinstein, LS Xie, T Qasem, A Wang, J Chen, M AF Weinstein, L. S. Xie, T. Qasem, A. Wang, J. Chen, M. TI The role of GNAS and other imprinted genes in the development of obesity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Review DE G protein; genomic imprinting; pseudohypoparathyroidism; Prader-Willi syndrome; Angelman's syndrome ID PROTEIN-ALPHA-SUBUNIT; PSEUDOHYPOPARATHYROIDISM TYPE 1A; DIET-INDUCED OBESITY; ALBRIGHT HEREDITARY OSTEODYSTROPHY; INCREASED INSULIN SENSITIVITY; G(S)ALPHA KNOCKOUT MICE; RECEPTOR-DEFICIENT MICE; BODY-MASS INDEX; MELANOCORTIN-4 RECEPTOR; ADIPOSE-TISSUE AB Genomic imprinting is an epigenetic phenomenon affecting a small number of genes, which leads to differential expression from the two parental alleles. Imprinted genes are known to regulate fetal growth and a 'kinship' or 'parental conflict' model predicts that paternally and maternally expressed imprinted genes promote and inhibit fetal growth, respectively. In this review we examine the role of imprinted genes in postnatal growth and metabolism, with an emphasis on the GNAS/Gnas locus. GNAS is a complex imprinted locus with multiple oppositely imprinted gene products, including the G-protein alpha-subunit G(s)alpha that is expressed primarily from the maternal allele in some tissues and the G(s)alpha isoform XL alpha s that is expressed only from the paternal allele. Maternal, but not paternal, G(s)alpha mutations lead to obesity in Albright hereditary osteodystrophy. Mouse studies show that this phenomenon is due to G(s)alpha imprinting in the central nervous system leading to a specific defect in the ability of central melanocortins to stimulate sympathetic nervous system activity and energy expenditure. In contrast mutation of paternally expressed XL alpha s leads to opposite metabolic effects in mice. Although these findings conform to the 'kinship' model, the effects of other imprinted genes on body weight regulation do not conform to this model. International Journal of Obesity (2010) 34, 6-17; doi:10.1038/ijo.2009.222; published online 20 October 2009 C1 [Weinstein, L. S.; Xie, T.; Qasem, A.; Wang, J.; Chen, M.] NIDDK, Signal Transduct Sect, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDK, Signal Transduct Sect, NIH, Bldg 10 Rm 8C101, Bethesda, MD 20892 USA. EM leew@mail.nih.gov OI Weinstein, Lee/0000-0002-1899-5152 FU National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health; US Department of Health and Human Services FX This work was supported by the Intramural Research Program of the National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services. NR 115 TC 34 Z9 34 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JAN PY 2010 VL 34 IS 1 BP 6 EP 17 DI 10.1038/ijo.2009.222 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 542TW UT WOS:000273519800003 PM 19844212 ER PT J AU Han, YY Dinse, GE Davis, DL AF Han, Yueh-Ying Dinse, Gregg E. Davis, Devra L. TI Temporal and Demographic Patterns of Non-Hodgkin's Lymphoma Incidence in Pennsylvania SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE non-Hodgkin's lymphoma; Pennsylvania; Surveillance, Epidemiology, and End Results Program (SEER); environmental exposure; occupational exposure; temporal patterns; demographic patterns ID MATERIALS PROCESSING FACILITIES; UNITED-STATES; CANCER INCIDENCE; RISK-FACTORS; PERSONAL USE; TIME TRENDS; EXPOSURE; EPIDEMIOLOGY; SUBTYPES; SURVEILLANCE AB Our study analyzed temporal and demographic patterns of non-Hodgkin's lymphoma (NHL) incidence in Pennsylvania and compared Pennsylvania time trends with national trends. Joinpoint and age-period-cohort analyses summarized sex- and race-specific NHL incidence time trends between 1985 and 2004. Ecologic analysis identified demographic factors associated with age-adjusted county-specific NHL incidence. NFIL incidence in Pennsylvania increased annually: 1.6% and 2.5% in white and black men and 1.6% and 3.2% in white and black women. National trends were similar, except for smaller increases in white men. Diffuse lymphoma appeared to be the major contributor to the increases. NHL incidence was higher in Pennsylvania Counties with greater Percentages of urban residents. NFIL incidence patterns in Pennsylvania were parallel to those seen nationally, with the highest rates Occurring in white men and in persons residing in urban areas. C1 [Han, Yueh-Ying; Davis, Devra L.] Univ Pittsburgh, Inst Canc, Ctr Environm Oncol, Dept Epidemiol,Grad Sch Publ Hlth, Pittsburgh, PA 15232 USA. [Dinse, Gregg E.] Natl Inst Environm Hlth Sci, NIH, Biostat Branch, Res Triangle Pk, NC USA. RP Han, YY (reprint author), Univ Pittsburgh, Inst Canc, Ctr Environm Oncol, Dept Epidemiol,Grad Sch Publ Hlth, 5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM hany2@upmc.edu FU NIH, National Institute of Environmental Health Sciences; Heinz Endowments; DSF Charitable Foundation; University of Pittsburgh Cancer Institute; Devra Lee Davis Charitable Foundation FX This research Was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. Support. to the Center For Environmental Oncology came from the Heinz Endowments, the DSF Charitable Foundation, the University of Pittsburgh Cancer Institute, and the Devra Lee Davis Charitable Foundation. NR 56 TC 1 Z9 1 U1 0 U2 2 PU HAMILTON HARDY PUBL INC PI ATTLEBORO PA 8 N MAIN ST, STE 404A, ATTLEBORO, MA 02703 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JAN-MAR PY 2010 VL 16 IS 1 BP 75 EP 84 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 546TU UT WOS:000273836500009 PM 20166322 ER PT J AU Jirles, B AF Jirles, Bill TI Environmental Unions: Labor and the Superfund SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Book Review C1 [Jirles, Bill] AFGE Local 2923 Union NIEHS, Durham, NC USA. RP Jirles, B (reprint author), AFGE Local 2923 Union NIEHS, Durham, NC USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU HAMILTON HARDY PUBL INC PI ATTLEBORO PA 8 N MAIN ST, STE 404A, ATTLEBORO, MA 02703 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JAN-MAR PY 2010 VL 16 IS 1 BP 85 EP 86 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 546TU UT WOS:000273836500010 ER PT J AU Kobayashi, M Ito, H Okumura, Y Mayahara, K Matsumoto, Y Hirakawa, J AF Kobayashi, Mika Ito, Hiroto Okumura, Yasuyuki Mayahara, Ken Matsumoto, Yoshio Hirakawa, Junichi TI HOSPITAL READMISSION IN FIRST-TIME ADMITTED PATIENTS WITH SCHIZOPHRENIA SMOKING PATIENTS HAD HIGHER HOSPITAL READMISSION RATE THAN NON-SMOKING PATIENTS SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE schizophrenia; smoking; hospital readmission ID CIGARETTE-SMOKING; NICOTINIC AGONIST; MENTAL-ILLNESS; HEALTH; POPULATION; DEPENDENCE; INPATIENTS; ADDICTION; CESSATION; SYMPTOMS AB Objectives To consider smoke-free policies for the patients with schizophrenia, the present study examined how smoking behavior is related to hospital readmission among patients with schizophrenia Methods A retro spective study was conducted in 2007 on 460 discharged patients with schizophrenia who voluntarily admitted in the participating psychiatric hospitals at first time We reviewed smoking status, readmissions, and other variables including socio demographic characteristics, process of care, and social functioning at discharge using the Global Assessment of Functioning scale (GAF) Results The rate of cigarette smoking in this study was 42 2% The rate of smoking was significantly higher in males (56 1%) than in females (26 2%) Mean GAF score at discharge was slightly higher in smoking patients than non-smoking patients (g = 0 18) Cox proportional hazard model revealed that hospital readmission rate was significantly higher in smoking patients than non smoking patients after controlling for all other variables (HR = 1 78) Conclusions Non-smoking patients had fewer hospital readmissions than smoking patients This finding could be a reason to promote cessation of smoking which might provide positive influences on prognosis of schizophrenia (Int l J Psychiatry in Medicine 2010 40 247 257) C1 [Kobayashi, Mika; Ito, Hiroto; Okumura, Yasuyuki] NIMH, Bethesda, MD 20892 USA. RP Ito, H (reprint author), 4-1-1 Ogawa Higashi Cho, Tokyo 1878553, Japan. NR 33 TC 7 Z9 10 U1 3 U2 3 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 2010 VL 40 IS 3 BP 247 EP 257 DI 10.2190/PM.40.3.b PG 11 WC Psychiatry SC Psychiatry GA 681RT UT WOS:000284335200002 PM 21166336 ER PT J AU Barker, CA Chang, M Chou, JF Zhang, Z Gutin, PH Beal, K Abrey, LE Iwamoto, FM AF Barker, C. A. Chang, M. Chou, J. F. Zhang, Z. Gutin, P. H. Beal, K. Abrey, L. E. Iwamoto, F. M. TI Concurrent Temozolomide (TMZ) Improves Survival, but Increases Toxicity, in Elderly Patients with Glioblastoma Multiforme (GBM) Treated with Standard (STD) or Abbreviated (ABR) Radiotherapy (RT) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Barker, C. A.; Chang, M.; Chou, J. F.; Zhang, Z.; Gutin, P. H.; Beal, K.; Abrey, L. E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Iwamoto, F. M.] NCI, Bethesda, MD 20892 USA. RI Barker, Christopher/I-9477-2012 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S167 EP S167 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775700356 ER PT J AU Chung, C Foltz, W Lindsay, P Burrell, K Kallehauge, J Wildgoose, P Camphausen, K Jaffray, D Zadeh, G Menard, C AF Chung, C. Foltz, W. Lindsay, P. Burrell, K. Kallehauge, J. Wildgoose, P. Camphausen, K. Jaffray, D. Zadeh, G. Menard, C. TI Intracranial Murine Tumor Investigation of Radiation and Antiangiogenic Agents using Serial MRI SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Chung, C.; Foltz, W.; Lindsay, P.; Kallehauge, J.; Wildgoose, P.; Jaffray, D.; Menard, C.] PMH, Toronto, ON, Canada. [Burrell, K.] SickKids Hosp, Toronto, ON, Canada. [Camphausen, K.] NCI, ROB, Bethesda, MD 20892 USA. [Zadeh, G.] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S663 EP S663 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701522 ER PT J AU Kamrava, M Kesarwala, A Lita, E Kaushal, A Ferrara, T Pazdur, M Tsang, K Gulley, J AF Kamrava, M. Kesarwala, A. Lita, E. Kaushal, A. Ferrara, T. Pazdur, M. Tsang, K. Gulley, J. TI Long Term Clinical Outcomes, Toxicity, and Immunologic Response of Patients Treated on a Phase II Trial with Definitive Radiation in Combination with a Viral Vaccine to Prostate-specific Antigen SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Kamrava, M.; Kesarwala, A.; Lita, E.; Kaushal, A.; Ferrara, T.; Pazdur, M.; Tsang, K.; Gulley, J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S126 EP S126 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775700268 ER PT J AU Kaushal, A Ko, C Hammoud, D Steffan-Smith, E Citrin, D Camphausen, K Warren, K AF Kaushal, A. Ko, C. Hammoud, D. Steffan-Smith, E. Citrin, D. Camphausen, K. Warren, K. TI The Role of Early Post Radiation MRI Scans in Children with Diffuse Intrinsic Pontine Glioma (DIPG) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Kaushal, A.; Ko, C.; Citrin, D.; Camphausen, K.] NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Hammoud, D.] Radiol & Imaging Sci, Bethesda, MD USA. [Hammoud, D.; Warren, K.] NCI, NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. RI Hammoud, Dima/C-2286-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S594 EP S595 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701372 ER PT J AU Kesarwala, AH Belard, A Dolney, D Eickstaedt, B McDonough, J Tochner, Z O'Connell, JJ AF Kesarwala, A. H. Belard, A. Dolney, D. Eickstaedt, B. McDonough, J. Tochner, Z. O'Connell, J. J. TI Electronic Integration of Radiation Oncology Clinics via Remote Proton Radiotherapy Telemedicine Solution SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Kesarwala, A. H.] Natl Canc Inst, Radiat Oncol Branch, Bethesda, MD USA. [Belard, A.] Henry M Jackson Fdn Advancement Mil Med, Rockville, MD USA. [Dolney, D.; Eickstaedt, B.; McDonough, J.; Tochner, Z.] Univ Penn, Philadelphia, PA 19104 USA. [O'Connell, J. J.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S491 EP S491 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701142 ER PT J AU Kil, W Camphausen, K Ondos, J Smart, D AF Kil, W. Camphausen, K. Ondos, J. Smart, D. TI Radiation Exposure of Parotid Gland during Whole-Brain Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Kil, W.; Camphausen, K.; Ondos, J.; Smart, D.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S606 EP S606 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701396 ER PT J AU Kim, GJ Koshy, M Horiba, MN Edelman, MJ Doyle, LA Burrows, WM Battafarano, RJ Krasna, MJ Hanlon, AL Suntharalingam, M AF Kim, G. J. Koshy, M. Horiba, M. N. Edelman, M. J. Doyle, L. A. Burrows, W. M. Battafarano, R. J. Krasna, M. J. Hanlon, A. L. Suntharalingam, M. TI The Benefit of Adjuvant Chemotherapy in Esophageal Cancer Patients with Residual Disease following Trimodality Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Kim, G. J.; Koshy, M.; Horiba, M. N.; Edelman, M. J.; Burrows, W. M.; Battafarano, R. J.; Suntharalingam, M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Doyle, L. A.] NCI, Rockville, MD USA. [Krasna, M. J.] St Josephs Med Ctr, Towson, MD USA. [Hanlon, A. L.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S72 EP S73 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775700156 ER PT J AU Ko, CJ Ning, H Camphausen, K Smith, S McNally, D Choyke, P Lita, E Coleman, N Menard, C Kaushal, A AF Ko, C. J. Ning, H. Camphausen, K. Smith, S. McNally, D. Choyke, P. Lita, E. Coleman, N. Menard, C. Kaushal, A. TI Phase II Trial of Combined High-dose-Rate Brachytherapy and External Beam Radiotherapy for Adenocarcinoma of the Prostate: Long-term Follow-up of Trial NCI 02-C-0207 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Ko, C. J.; Ning, H.; Camphausen, K.; Smith, S.; McNally, D.; Choyke, P.; Lita, E.; Coleman, N.; Kaushal, A.] NCI, Bethesda, MD 20892 USA. [Menard, C.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S344 EP S344 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775700748 ER PT J AU Milano, MT Li, H Constine, LS Travis, LB AF Milano, M. T. Li, H. Constine, L. S. Travis, L. B. TI Long-term Survival among Hodgkin Lymphoma (HL) Patients with Non-small Cell Lung Cancer (NSCLC): A Population-based Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Milano, M. T.; Constine, L. S.; Travis, L. B.] Univ Rochester, Rochester, NY USA. [Li, H.] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S544 EP S545 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701261 ER PT J AU Rosenstein, BS Elliott, RM Alsner, J Bentzen, SM Chang-Claude, J De Ruysscher, D Dunning, A Seminara, D West, CML AF Rosenstein, B. S. Elliott, R. M. Alsner, J. Bentzen, S. M. Chang-Claude, J. De Ruysscher, D. Dunning, A. Seminara, D. West, C. M. L. CA Radiogenomics Consortium TI Establishment of an International Radiogenomics Consortium SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Rosenstein, B. S.] Mt Sinai Sch Med, New York, NY USA. [Elliott, R. M.; Radiogenomics Consortium] Univ Manchester, Christie Hosp, Manchester, Lancs, England. [Alsner, J.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Bentzen, S. M.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Chang-Claude, J.] German Canc Res Ctr, D-6900 Heidelberg, Germany. [De Ruysscher, D.] Maastricht Univ, Med Ctr, Maastricht, Netherlands. [Dunning, A.] Univ Cambridge, Cambridge, England. [Seminara, D.] NCI, Bethesda, MD 20892 USA. RI Bentzen, Soren/E-3997-2012; Alsner, Jan/A-3056-2009 OI Bentzen, Soren/0000-0002-7444-7564; Alsner, Jan/0000-0002-5395-3193 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S664 EP S664 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701524 ER PT J AU Shabason, J Zudaire, E Zhao, S Shankavaram, UT Tandle, AT Tofilon, PJ Camphausen, K AF Shabason, J. Zudaire, E. Zhao, S. Shankavaram, U. T. Tandle, A. T. Tofilon, P. J. Camphausen, K. TI The Profile of Glioma Microvesicles After Irradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Shabason, J.; Zudaire, E.; Zhao, S.; Shankavaram, U. T.; Tandle, A. T.; Camphausen, K.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Shabason, J.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. [Tofilon, P. J.] Univ S Florida, H Lee Moffitt Canc Ctr, Drug Discovery Program, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S130 EP S130 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775700277 ER PT J AU Shankavaram, UT Bredel, M Tofilon, P Camphausen, K AF Shankavaram, U. T. Bredel, M. Tofilon, P. Camphausen, K. TI Predictive Pre-clinical Modeling of Glioblastoma Multiforme SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Shankavaram, U. T.; Camphausen, K.] NCI, Bethesda, MD 20892 USA. [Bredel, M.] NW Univ Feinberg Sch Med, Chicago, IL USA. [Tofilon, P.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S492 EP S493 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701145 ER PT J AU Sproull, M Avondoglio, D Meushaw, T Shankavaram, U Camphausen, K AF Sproull, M. Avondoglio, D. Meushaw, T. Shankavaram, U. Camphausen, K. TI Plasma Flt3-ligand as a Biomarker for Radiation Exposure SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Sproull, M.; Avondoglio, D.; Meushaw, T.; Shankavaram, U.; Camphausen, K.] NCI, NIH, ROB, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S635 EP S635 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701462 ER PT J AU Tao, R Bisht, KS Nguyen, P Ozden, O Gius, D AF Tao, R. Bisht, K. S. Nguyen, P. Ozden, O. Gius, D. TI Post-translational Regulation of Superoxide Dismutase as a Tumor-suppressor Effect of SIRT3 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Tao, R.; Bisht, K. S.; Nguyen, P.; Ozden, O.; Gius, D.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S89 EP S89 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775700192 ER PT J AU Thomas, CR Glover, KZ Constantino, JP Feingold, E Wilson, JW AF Thomas, C. R. Glover, K. Z. Constantino, J. P. Feingold, E. Wilson, J. W. TI Comparison of African American (AA) and White (W) Patients with Respect to Radiotherapy (RT) Delivery in National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Treatment Trials SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Thomas, C. R.] Oregon Hlth & Sci Univ, Portland, OR USA. [Glover, K. Z.; Constantino, J. P.; Feingold, E.; Wilson, J. W.] Univ Pittsburgh, Pittsburgh, PA USA. [Constantino, J. P.; Wilson, J. W.] NSABP, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S10 EP S11 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775700023 ER PT J AU Wernick, MH Saleh, AD Savage, JE Mitchell, JB Simone, NL AF Wernick, M. H. Saleh, A. D. Savage, J. E. Mitchell, J. B. Simone, N. L. TI MicroRNA Let-7 Exhibits Altered Expression in Response to Ionizing Radiation by a Mechanism Other Than DNA Double Strand Break Repair SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Wernick, M. H.; Saleh, A. D.; Savage, J. E.; Mitchell, J. B.; Simone, N. L.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S632 EP S632 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701455 ER PT J AU Yoo, S Cerna, D Li, H Flaherty, S Takebe, N Coleman, C AF Yoo, S. Cerna, D. Li, H. Flaherty, S. Takebe, N. Coleman, C. TI NAPRT1 and p53 Status in Cancer and Normal Cells Modulate Induction of ROS Induced by GMX1777/1778: Implication for Synthetic Lethality in Tumors Defective in NAPRT1 and p53 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Yoo, S.; Takebe, N.] NCI, Rockville, MD USA. [Cerna, D.; Li, H.; Flaherty, S.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Coleman, C.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S656 EP S656 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701508 ER PT J AU Zhuge, Y Xie, H Miller, RW AF Zhuge, Y. Xie, H. Miller, R. W. TI Accelerating Monte Carlo Simulation for Radiotherapy Dose Calculation using a Massively Parallel Graphics Processing Unit SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-For-Radiation-Oncology CY OCT 31-NOV 04, 2010 CL San Diego, CA SP Amer Soc Radiation Oncol C1 [Zhuge, Y.; Xie, H.; Miller, R. W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2010 VL 78 IS 3 SU S BP S804 EP S805 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 740EZ UT WOS:000288775701833 ER PT J AU Lu, TP Lai, LC Lin, BI Chen, LH Hsiao, TH Liber, HL Cook, JA Mitchell, JB Tsai, MH Chuang, EY AF Lu, Tzu-Pin Lai, Liang-Chuan Lin, Be-I Chen, Li-Han Hsiao, Tzu-Hung Liber, Howard L. Cook, John A. Mitchell, James B. Tsai, Mong-Hsun Chuang, Eric Y. TI DISTINCT SIGNALING PATHWAYS AFTER HIGHER OR LOWER DOSES OF RADIATION IN THREE CLOSELY RELATED HUMAN LYMPHOBLAST CELL LINES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Microarray; Human lymphoblast cells; Radiation; Signaling pathway; p53 ID NF-KAPPA-B; GENE-EXPRESSION; IONIZING-RADIATION; P53 STATUS; PROSTATE CARCINOMA; INDUCED APOPTOSIS; GENOTOXIC STRESS; CANCER-CELLS; ACTIVATION; E2F4 AB Purpose: The tumor suppressor p53 plays an essential role in cellular responses to DNA damage caused by ionizing radiation; therefore, this study aims to further explore the role that p53 plays at different doses of radiation. Materials and Methods: The global cellular responses to higher-dose (10 Gy) and lower dose (iso-survival dose, i.e., the respective D0 levels) radiation were analyzed using microarrays in three human lymphoblast cell lines with different p53 status: TK6 (wild-type p53), NH32 (p53-null), and WTK1 (mutant p53). Total RNAs were extracted from cells harvested at 0, 1, 3, 6, 9, and 24 h after higher and lower dose radiation exposures. Template-based clustering, hierarchical clustering, and principle component analysis were applied to examine the transcriptional profiles. Results: Differential expression profiles between 10 Gy and iso-survival radiation in cells with different p53 status were observed. Moreover, distinct gene expression patterns were exhibited among these three cells after 10 Gy radiation treatment, but similar transcriptional responses were observed in TK6 and NH32 cells treated with iso-survival radiation. Conclusions: After 10 Gy radiation exposure, the p53 signaling pathway played an important role in TK6, whereas the NFkB signaling pathway appeared to replace the role of p53 in WTK1. In contrast, after iso-survival radiation treatment, E2F4 seemed to play a dominant role independent of p53 status. This study dissected the impacts of p53, NFkB and E2F4 in response to higher or lower doses of gamma-irradiation. (C) 2010 Elsevier Inc. C1 [Lai, Liang-Chuan; Lin, Be-I; Chen, Li-Han; Hsiao, Tzu-Hung; Tsai, Mong-Hsun] Natl Taiwan Univ, Res Ctr Med Excellence, Taipei 10764, Taiwan. [Lu, Tzu-Pin; Chuang, Eric Y.] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 10764, Taiwan. [Lai, Liang-Chuan; Chuang, Eric Y.] Natl Taiwan Univ, Grad Inst Physiol, Taipei 10764, Taiwan. [Hsiao, Tzu-Hung; Chuang, Eric Y.] Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. [Tsai, Mong-Hsun] Natl Taiwan Univ, Inst Biotechnol, Taipei 10764, Taiwan. [Chuang, Eric Y.] Natl Taiwan Univ, Dept Life Sci, Taipei 10764, Taiwan. [Chuang, Eric Y.] Natl Taiwan Univ, Grad Inst Epidemiol, Taipei 10764, Taiwan. [Liber, Howard L.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. [Cook, John A.; Mitchell, James B.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tsai, MH (reprint author), Natl Taiwan Univ, Res Ctr Med Excellence, Taipei 10764, Taiwan. EM motiont@ntu.edu.tw; chuangey@ntu.edu.tw RI Lai, Liang-chuan/B-4768-2009; OI Lai, Liang-chuan/0000-0002-3913-5338; LU, TZU-PIN/0000-0003-3697-0386 FU National Taiwan University, Taiwan, ROC [95R0066-BM01-01, 97R0066-08]; National Science Council, Taiwan, ROC [NSC 95-2314-B-002-112-MY3, NSC 97-2627-B-002-009, NSC 98-2314-b-002-065-MY3]; Department of Health, Taiwan, ROC [DOH96-TD-G-111-014] FX Supported by 95R0066-BM01-01 and 97R0066-08 from National Taiwan University, Taiwan, ROC, NSC 95-2314-B-002-112-MY3, NSC 97-2627-B-002-009 and NSC 98-2314-b-002-065-MY3 from National Science Council, Taiwan, ROC; DOH96-TD-G-111-014 from Department of Health, Taiwan, ROC. 1These authors contributed equally to this work. NR 36 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2010 VL 76 IS 1 BP 212 EP 219 DI 10.1016/j.ijrobp.2009.08.015 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 541TA UT WOS:000273442300033 PM 20005454 ER PT J AU Celentano, DD Mayer, KH Pequegnat, W Abdala, N Green, AM Handsfield, HH Hartwell, TD AF Celentano, David D. Mayer, Kenneth H. Pequegnat, Willo Abdala, Nadia Green, Annette M. Handsfield, H. Hunter Hartwell, Tyler D. CA Natl Inst Mental Hlth TI Prevalence of Sexually Transmitted Diseases and Risk Behaviors from the NIMH Collaborative HIV/STD Prevention Trial SO INTERNATIONAL JOURNAL OF SEXUAL HEALTH LA English DT Article DE HIV prevention; sexually transmitted diseases; behavioral risk factors; international ID CLINIC PATIENTS; UNITED-STATES; INFECTIONS; EPIDEMICS; ALCOHOL; TRANSMISSION; STRATEGIES; SEEKING; CARE AB This cross-sectional study describes the baseline prevalence and correlates of common bacterial and viral sexually transmitted diseases (STDs) and risk behaviors among individuals at high risk for HIV recruited in five low- and middle-income countries. Correlations of risk behaviors and demographic factors with prevalent STDs and the association of STDs with HIV prevalence are examined. Between 2,212 and 5,543 participants were recruited in each of five countries (China, India, Peru, Russia, and Zimbabwe). Standard protocols were used to collect behavioral risk information and biological samples for STD testing. Risk factors for HIV/STD prevalence were evaluated using logistic regression models. STD prevalence was significantly higher for women than men in all countries, and the most prevalent STD was Herpes simplex virus-type 2 (HSV-2). HIV prevalence was generally low (below 5%) except in Zimbabwe (30% among women, 11.7% among men). Prevalence of bacterial STDs was generally low (below 5% for gonorrhea and under 7% for syphilis in all sites), with the exception of syphilis among female sex workers in India. Behavioral and demographic risks for STDs varied widely across the five study sites. Common risks for STDs included female gender, increasing number of recent sex partners, and in some sites, older age, particularly for chronic STDs (i.e., HSV-2 and HIV). Prevalence of HIV was not associated with STDs except in Zimbabwe, which showed a modest correlation between HIV and HSV-2 prevalence (Pearson coefficient = .55). These findings underscore the heterogeneity of global STD and HIV epidemics and suggest that local, focused interventions are needed to achieve significant declines in these infections. C1 [Pequegnat, Willo] NIMH, Int AIDS Prevent Res, Ctr Mental Hlth Res AIDS, NIH, Bethesda, MD 20892 USA. [Celentano, David D.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Mayer, Kenneth H.] Brown Univ, Sch Med, Miriam Hosp, Providence, RI 02912 USA. [Abdala, Nadia] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Green, Annette M.; Hartwell, Tyler D.] Res Triangle Inst Int, Durham, NC USA. [Handsfield, H. Hunter] Battelle Ctr Publ Hlth Res & Evaluat, Seattle, WA USA. RP Pequegnat, W (reprint author), NIMH, Int AIDS Prevent Res, Ctr Mental Hlth Res AIDS, NIH, 6001 Execut Blvd,Room 6219,MSC 9619, Bethesda, MD 20892 USA. EM wpequegn@mail.nih.gov FU NIMH NIH HHS [U10 MH061513] NR 26 TC 3 Z9 3 U1 0 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1931-7611 J9 INT J SEX HEALTH JI Int. J. Sex. Health PY 2010 VL 22 IS 4 BP 272 EP 284 AR PII 930795371 DI 10.1080/19317611.2010.494092 PG 13 WC Psychology, Clinical; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Psychology; Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 697JS UT WOS:000285510400006 PM 25400718 ER PT J AU Weintrob, AC Gu, W Qin, J Robertson, J Ganeson, A Crum-Cianflone, NF Landrum, ML Wortmann, GW Foliman, D Agan, BK AF Weintrob, A. C. Gu, W. Qin, J. Robertson, J. Ganeson, A. Crum-Cianflone, N. F. Landrum, M. L. Wortmann, G. W. Foliman, D. Agan, B. K. TI Syphilis co-infection does not affect HIV disease progression SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE HIV; syphilis; AIDS; mortality; cohort ID CD4 CELL COUNTS; VIRAL LOAD; INFECTED PATIENTS AB HIV and syphilis are often seen as co-infections since they share a common mode of transmission. During episodes of syphilis, CD4 counts transiently decrease and HIV viral loads increase; however, the effect of syphilis co-infection on HIV disease progression (time to AIDS or death) is unclear. We analysed prospectively collected information on 2239 persons with estimated dates of HIV seroconversion (205 [9.2%] with confirmed syphilis and 66 [2.9%] with probable syphilis) in order to determine the effect of syphilis co-infection on HIV disease progression. In multivariate models censored at highly active antiretroviral therapy (HAART) initiation or last visit, adjusting for CD4 count, age, race, gender, and hepatitis B and C status, syphilis (confirmed + probable) was not associated with increased hazard of AIDS or death (hazard ratio 0.99, 95% CI 0.73-1.33). Treating HAART as a time-varying covariate or limiting the analysis to only confirmed syphilis cases did not significantly alter the results. Despite transient changes in CD4 counts and viral loads, syphilis does not appear to affect HIV disease progression. C1 [Weintrob, A. C.; Ganeson, A.; Crum-Cianflone, N. F.; Landrum, M. L.; Agan, B. K.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD USA. [Weintrob, A. C.; Wortmann, G. W.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Gu, W.] SAIC Frederick, Biostat Res Branch, Frederick, MD USA. [Qin, J.; Foliman, D.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Robertson, J.; Landrum, M. L.] San Antonio Mil Med Ctr, San Antonio, TX USA. [Crum-Cianflone, N. F.] Naval Med Ctr San Diego, San Diego, CA USA. [Ganeson, A.] Natl Naval Med Ctr, Bethesda, MD USA. RP Weintrob, AC (reprint author), 6900 Georgia Ave NW,Bldg 2,Ward 63,Room 6312, Washington, DC 20307 USA. EM Amy.Weintrob@amedd.army.mil OI Agan, Brian/0000-0002-5114-1669 FU Uniformed Services University of the Health Sciences (USUHS); HHS/NIH/NIAID/DCR [HU0001-05-2-0011]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases FX We would like to thank the patients without whom none of this work would be possible. We would also like to thank the research coordinators and support staff who diligently work on the DoD HIV NHS as well as the members of the IDCRP HIV Working Group. Support for this work was provided by the Infectious Disease Clinical Research Program (IDCRP) of the Uniformed Services University of the Health Sciences (USUHS). The IDCRP is a Department of Defense tri-service programme executed through USUHS and the Henry M Jackson Foundation for the Advancement of Military Medicine (HJF), in collaboration with HHS/NIH/NIAID/DCR through Interagency Agreement HU0001-05-2-0011. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting the views of the Departments of the Army, Navy, Air Force or the Department of Defense. The authors have no commercial or other association that might pose a conflict of interest.; This project has also been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 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, commercial products or organizations imply endorsement by the US Government. This research was supported in part by the National Institute of Allergy and Infectious Diseases. NR 8 TC 8 Z9 8 U1 0 U2 3 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD JAN PY 2010 VL 21 IS 1 BP 57 EP 59 DI 10.1258/ijsa.2009.009164 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 549TY UT WOS:000274078400012 PM 19933204 ER PT J AU Koonin, EV Yutin, N AF Koonin, Eugene V. Yutin, Natalya TI Origin and Evolution of Eukaryotic Large Nucleo-Cytoplasmic DNA Viruses SO INTERVIROLOGY LA English DT Article DE Bacteriophage; Eukaryogenesis; Nucleo-cytoplasmic large DNA viruses, evolution; Phylogenetic analysis ID COMPARATIVE GENOMICS; GIANT VIRUSES; PSI-BLAST; MIMIVIRUS; LIFE; TREE; ACQUISITION; EMERGENCE; VIROPHAGE; SEQUENCE AB Background/Aims: The nucleo-cytoplasmic large DNA viruses (NCLDV) constitute an apparently monophyletic group that consists of 6 families of viruses infecting a broad variety of eukaryotes. A comprehensive genome comparison and maximum-likelihood reconstruction of NCLDV evolution reveal a set of approximately 50 conserved genes that can be tentatively mapped to the genome of the common ancestor of this class of eukaryotic viruses. We address the origins and evolution of NCLDV. Results: Phylogenetic analysis indicates that some of the major clades of NCLDV infect diverse animals and protists, suggestive of early radiation of the NCLDV, possibly concomitant with eukaryogenesis. The core NCLDV genes seem to have originated from different sources including homologous genes of bacteriophages, bacteria and eukaryotes. These observations are compatible with a scenario of the origin of the NCLDV at an early stage of the evolution of eukaryotes through extensive mixing of genes from widely different genomes. Conclusions: The common ancestor of the NCLDV probably evolved from a bacteriophage as a result of recruitment of numerous eukaryotic and some bacterial genes, and concomitant loss of the majority of phage genes except for a small core of genes coding for proteins essential for virus genome replication and virion formation. Copyright (C) 2010 S. Karger AG, Basel C1 [Koonin, Eugene V.; Yutin, Natalya] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU DHHS (NIH, National Library of Medicine) FX The authors' research is supported by the DHHS intramural program (NIH, National Library of Medicine). NR 41 TC 73 Z9 75 U1 1 U2 18 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PY 2010 VL 53 IS 5 BP 284 EP 292 DI 10.1159/000312913 PG 9 WC Virology SC Virology GA 613CV UT WOS:000278955300005 PM 20551680 ER PT S AU Kumar, V Malhotra, SV AF Kumar, Vineet Malhotra, Sanjay V. BE Malhotra, SV TI Ionic Liquids as Pharmaceutical Salts: A Historical Perspective SO IONIC LIQUID APPLICATIONS: PHARMACEUTICALS, THERAPEUTICS, AND BIOTECHNOLOGY SE ACS Symposium Series LA English DT Proceedings Paper CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc ID CELL-LINE HELA; CYTOTOXICITY; SOLUBILITY AB Design and synthesis of pharmaceutically acceptable salts is one of the prime aspect of drug development. An estimated half of all drugs used in medicine are administered as salts. The salt formation of drug candidates has been recognized as an essential preformulation task. Salt formation of APIs can improve their aqueous solubility, industrial processing, safety aspects and sometimes biological properties. These properties can be further enhanced by changing counterion of the active component. Though there is no concerned effort of finding applications of ionic liquids in the pharmaceutical arena in recent years, a detailed survey of the literature shows that pharmaceutical salts having properties now termed as 'ionic liquids' have existed for a long time. In this chapter a historical overview of 'ionic liquid like pharmaceutical salts', their importance and application in drug development has been described. C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Kumar, V (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov; malhotrasa@mail.nih.gov NR 17 TC 9 Z9 10 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2547-3 J9 ACS SYM SER JI ACS Symp. Ser. PY 2010 VL 1038 BP 1 EP 12 PG 12 WC Chemistry, Applied; Chemistry, Multidisciplinary SC Chemistry GA BVR22 UT WOS:000292522900001 ER PT S AU Kumar, V Malhotra, SV AF Kumar, Vineet Malhotra, Sanjay V. BE Malhotra, SV TI Antitumor Activity of Ionic Liquids on Human Tumor Cell Lines SO IONIC LIQUID APPLICATIONS: PHARMACEUTICALS, THERAPEUTICS, AND BIOTECHNOLOGY SE ACS Symposium Series LA English DT Proceedings Paper CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc ID PHARMACEUTICAL INGREDIENTS; CYTOTOXICITY; SCREEN; HELA AB Ionic liquids (ILs) have emerged as new class of compounds with unique properties and potential to tailor their physiochemical properties. However, very limited studies have been reported on their toxicity and safety causing concern for their use for biomedical applications, specifically as therapeutic agents and drugs. Our studies towards finding therapeutic applications of ILs for the first time demonstrated the anti-cancer activity and cytotoxicity of three different classes of ionic liquids (imidazolium, phosphonium and ammonium) on National Cancer Institute's 60 human tumor cell lines. In this chapter an overview of these results is presented through representative examples. The preleminary structure-activity relationship (SAR.) showed that the chain length of alkyl substitution on the cations plays crucial role towards anti-tumor activity and cytotoxicity of ionic liquids. In general, phosphonium-based ILs were found to be more active and less cytotoxic as compared to their ammonium amd imidazolium conterparts. In-vitro cell line data and hollow fiber study has demonstrated the potential of ILs to be developed as therapeutic agent. C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Kumar, V (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov; malhotrasa@mail.nih.gov NR 27 TC 5 Z9 5 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2547-3 J9 ACS SYM SER JI ACS Symp. Ser. PY 2010 VL 1038 BP 91 EP + PG 13 WC Chemistry, Applied; Chemistry, Multidisciplinary SC Chemistry GA BVR22 UT WOS:000292522900008 ER PT B AU Gulyani, S Mattson, MP AF Gulyani, Seema Mattson, Mark P. BE Yehuda, S Mostofsky, DI TI Alzheimer's Dementia SO IRON DEFICIENCY AND OVERLOAD: FROM BASIC BIOLOGY TO CLINICAL MEDICINE SE Nutrition and Health Series LA English DT Article; Book Chapter DE Alzheimer's disease; amyloid; cognitive impairment; hydroxynonenal; neurofibrillary; tangles; presenilin-1; synaptic dysfunction ID AMYLOID-BETA-PEPTIDE; MEMBRANE-LIPID PEROXIDATION; IRON-RESPONSIVE ELEMENT; APOLIPOPROTEIN-E; OXIDATIVE STRESS; A-BETA; HIPPOCAMPAL-NEURONS; MOUSE MODEL; DISEASE HIPPOCAMPUS; TRANSGENIC MOUSE AB The disability caused by Alzheimer's disease (AD) is increasing worldwide with 4.6 million newly diagnosed patients every year. Age-related oxidative stress appears to be an important contributor to the amyloid pathology and neuronal degeneration of AD. Iron homeostasis is altered in AD patients. Iron promotes the formation of amyloid plaques and neurofibrillary tangles, which are the hallmarks of the disease. Iron also causes synaptic dysfunction by altering cell membrane integrity and impairing the function of membrane-bound proteins. Future treatments for AD may include dietary modifications and drugs that reduce the amount of toxic free iron, or that protect cells against iron toxicity. C1 [Gulyani, Seema; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Gulyani, S (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NR 77 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 978-1-934115-22-0 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 241 EP 249 DI 10.1007/978-1-59745-462-9_14 D2 10.1007/978-1-59745-462-9 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BMR08 UT WOS:000273376400014 ER PT B AU Sempos, CT Looker, AC McGee, DL Rehm, J AF Sempos, Christopher T. Looker, Anne C. McGee, Daniel L. Rehm, Juergen BE Yehuda, S Mostofsky, DI TI Iron and Heart Disease: A Review of the Epidemiologic Data SO IRON DEFICIENCY AND OVERLOAD: FROM BASIC BIOLOGY TO CLINICAL MEDICINE SE Nutrition and Health Series LA English DT Review; Book Chapter DE Iron; ferritin; CHD; heart disease; hemochromatosis; epidemiology ID CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; LOW-DENSITY-LIPOPROTEIN; EASTERN FINNISH MEN; HIGH BLOOD CHOLESTEROL; TREATMENT PANEL-III; NCEP EXPERT PANEL; SERUM FERRITIN; CAROTID ATHEROSCLEROSIS; UNITED-STATES AB In 1981, Dr. Jerome Sullivan proposed the hypothesis that the risk of coronary heart disease (CHD) increases in a positive fashion as body iron stores increase. Serum ferritin and other less precise measures of body iron stores have been used in those studies to test the hypothesis. Serum ferritin was not significantly related to risk of developing CHD in the vast majority of the observational cohort studies, case-control, or cross-sectional studies. In an underpowered clinical trial, those receiving phlebotomy to lower body stores of iron did not have a significantly lower risk of death from all causes (primary endpoint) or of death plus non-fatal heart attack or stroke compared to controls. The presence of the Cys282Tyr mutation, which accounts for most of the cases of hemochromatosis, was not found to be associated with CHD risk in two meta-analysis studies. At present, the vast majority of the epidemiological data does not support the hypothesis that body iron stores are directly related to the risk of developing CHD. C1 [Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Rehm, Juergen] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [McGee, Daniel L.] Florida State Univ, Coll Arts & Sci, Dept Stat, Tallahassee, FL 32306 USA. [Looker, Anne C.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Sempos, CT (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA. NR 118 TC 3 Z9 5 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-22-0 J9 NUTR HEALTH SER JI Nutr. Health Ser. PY 2010 BP 279 EP 298 DI 10.1007/978-1-59745-462-9_16 D2 10.1007/978-1-59745-462-9 PG 20 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BMR08 UT WOS:000273376400016 ER PT S AU Bertram, R Sherman, A Satin, LS AF Bertram, Richard Sherman, Arthur Satin, Leslie S. BE Islam, MS TI Electrical Bursting, Calcium Oscillations, and Synchronization of Pancreatic Islets SO ISLETS OF LANGERHANS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter DE Bursting; Insulin secretion; Islet; Pulsatility; Oscillations ID PULSATILE INSULIN-SECRETION; SENSITIVE K+ CHANNELS; CYTOPLASMIC FREE CA2+; GLUCOSE-INDUCED OSCILLATIONS; PURINE NUCLEOTIDE CYCLE; SINGLE-MOUSE ISLETS; BETA-CELLS; GLYCOLYTIC OSCILLATIONS; ENDOPLASMIC-RETICULUM; IN-VIVO AB Oscillations are an integral part of insulin secretion and are ultimately due to oscillations in the electrical activity of pancreatic beta-cells, called bursting. In this chapter we discuss islet bursting oscillations and a unified biophysical model for this multi-scale behavior. We describe how electrical bursting is related to oscillations in the intracellular Ca2+ concentration within beta-cells and the role played by metabolic oscillations. Finally, we discuss two potential mechanisms for the synchronization of islets within the pancreas. Some degree of synchronization must occur, since distinct oscillations in insulin levels have been observed in hepatic portal blood and in peripheral blood sampling of rats, dogs, and humans. Our central hypothesis, supported by several lines of evidence, is that insulin oscillations are crucial to normal glucose homeostasis. Disturbance of oscillations, either at the level of the individual islet or at the level of islet synchronization, is detrimental and can play a major role in type 2 diabetes. C1 [Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. [Satin, Leslie S.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Satin, Leslie S.] Univ Michigan, Sch Med, Brehm Diabet Ctr, Ann Arbor, MI 48109 USA. [Sherman, Arthur] NIH, Lab Biol Modeling, Bethesda, MD 20892 USA. RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu; asherman@nih.gov; lsatin@umich.edu FU Intramural NIH HHS [Z01 DK013027-02]; NIDDK NIH HHS [R01 DK 46409, R01 DK046409] NR 109 TC 24 Z9 24 U1 0 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-90-481-3270-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2010 VL 654 BP 261 EP 279 DI 10.1007/978-90-481-3271-3_12 D2 10.1007/978-90-481-3271-3 PG 19 WC Cell Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Cell Biology; General & Internal Medicine; Research & Experimental Medicine GA BOY83 UT WOS:000278074700012 PM 20217502 ER PT J AU Kafulafula, G Hoover, DR Taha, TE Thigpen, M Li, Q Fowler, MG Kunwenda, NI Nkanaunena, K Mipando, L Mofenson, LM AF Kafulafula, George Hoover, Donald R. Taha, Taha E. Thigpen, Michael Li, Qing Fowler, Mary Glenn Kunwenda, Newton I. Nkanaunena, Kondwani Mipando, Linda Mofenson, Lynne M. TI Frequency of Gastroenteritis and Gastroenteritis-Associated Mortality With Early Weaning in HIV-1-Uninfected Children Born to HIV-Infected Women in Malawi SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE breastfeeding; weaning; gastroenteritis; mortality; HIV-exposed infant ID HUMAN-IMMUNODEFICIENCY-VIRUS; LATE POSTNATAL TRANSMISSION; PROPHYLAXIS; COUNTRIES; TRIAL AB Background: We assessed gastroenteritis (GE) burden in 2 randomized trials conducted in Malawi to reduce postnatal HIV transmission before and after World Health Organization recommendations regarding exclusive breastfeeding for HIV-exposed infants were adopted. The 2 trials. were the nevirapine/AZT (NVAZ, 2000-2003 with prolonged breastfeeding) and the Postexposure Prophylaxis to the Infant (PEPI, 2004-2007 with breastfeeding cessation by 6 months). Methods: From NVAZ and PEPI trials data, GE frequency through age 12 months among HIV-negative exposed infants was evaluated. Overall and GE-related cumulative mortality rates were estimated using Kaplan-Meier curves. Results: The frequency of at least one GE-related hospitalization was greater in PEPI vs. NVAZ after age 6 months (respectively, 2.9% vs. 0.1%, at 7-9 months and 1.6% vs. 0.2% at 10-12 months, P < 0.001). Cumulative GE-related mortality was significantly higher in PEPI than in NVAZ after age 6 months; at ages 9 and 12 months GE-related mortality was 19 and 24 per 1000 infants in PEPI vs. 7 and 12 per 1000 infants in NVAZ (P = 0.0002). Conclusions: Early weaning was associated with increased risk of severe GE and GE-related mortality among HIV-exposed infants. Strategies are urgently needed which allow longer breastfeeding while reducing the risk of HIV breast milk transmission in resource-limited settings. C1 [Taha, Taha E.; Li, Qing; Kunwenda, Newton I.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Kafulafula, George] Univ Malawi, Coll Med, Dept Obstet & Gynaecol, Blantyre, Malawi. [Hoover, Donald R.] Rutgers State Univ, Dept Stat, New Brunswick, NJ 08903 USA. [Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. [Thigpen, Michael; Mofenson, Lynne M.] Ctr Dis Control & Prevent, Epidemiol Branch, Div HIV AIDS Prevent Surveillance & Epidemiol, Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. [Fowler, Mary Glenn] Makerere Univ, Mulago Hosp, Kampala, Uganda. [Nkanaunena, Kondwani; Mipando, Linda] Johns Hopkins Univ, Coll Med, Minist Hlth, Res Project, Blantyre, Malawi. [Thigpen, Michael; Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. RP Taha, TE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM ttaha@jhsph.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU Centers for Disease Control and Prevention, Atlanta, GA; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, Rockville, MD [5ROTWO1199]; Fogarty International Centre; Doris Duke Charitable Foundation, New York FX Supported by Centers for Disease Control and Prevention, Atlanta, GA and Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, which funded the PEPI study. The NVAZ studies were funded by Fogarty International Centre, National Institutes of Health (AIDS FIRCA Award No. 5ROTWO1199 and Supplement) and the Doris Duke Charitable Foundation, New York. NR 22 TC 65 Z9 67 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2010 VL 53 IS 1 BP 6 EP 13 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 538KG UT WOS:000273182400003 PM 19844183 ER PT J AU Onyango-Makumbi, C Bagenda, D Mwatha, A Omer, SB Musoke, P Mmiro, F Zwerski, SL Kateera, BA Musisi, M Fowler, MG Jackson, JB Guay, LA AF Onyango-Makumbi, Carolyne Bagenda, Danstan Mwatha, Antony Omer, Saad B. Musoke, Philippa Mmiro, Francis Zwerski, Sheryl L. Kateera, Brenda Asiimwe Musisi, Maria Fowler, Mary Glenn Jackson, J. Brooks Guay, Laura A. TI Early Weaning of HIV-Exposed Uninfected Infants and Risk of Serious Gastroenteritis: Findings from Two Perinatal HIV Prevention Trials in Kampala, Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA DE HIV; infants; breastfeeding cessation; serious gastroenteritis; mortality; Uganda ID TO-CHILD TRANSMISSION; RANDOMIZED-TRIAL; INFECTIOUS-DISEASES; PROSPECTIVE COHORT; SOUTH-AFRICA; ZIDOVUDINE; PROPHYLAXIS; MOTHERS; INTRAPARTUM; MORTALITY AB Objective: To assess serious gastroenteritis risk and mortality associated with early cessation of breastfeeding in infants, enrolled in 2 prevention of maternal-to-child HIV-transmission trials in Uganda. Methods: We used hazard rates to evaluate serious gastroenteritis events by month of age and mortality among HIV-exposed uninfected infants enrolled in the HIV Network for Prevention Trials (HIVNET 012) (1997-2001) and HIV hyperimmune globulin (HIVIGLOB)/nevirapine (NVP) (2004-2007) trials. HIV-infected mothers were counseled using local infant feeding guidelines current at the time. Results: Breastfeeding cessation occurred earlier in HIVIGLOB/NVP compared with HIVNET 012 (median 4.0 versus 9.3 months, P < 0.001). Rates of serious gastroenteritis were higher in HIVIGLOB/NVP (8.0/1000 child-months) than in HIVNET 012 (3.1/1000 child-months; P < 0.001). Serious gastroenteritis events also peaked earlier at 3-4 and 7-8 months (16.2/1000 and 15.0/1000 child-months, respectively) compared with HIVNET 012 at 9-10 months (20.8/1000 child-months). All cause infant mortality did not statistically differ between the HIVIGLOB/NVP and the HIVNET 012 trials [3.2/1000 versus 2.0/1000 child-months, respectively (P = 0.10)]. Conclusions: Early breastfeeding cessation seen in the HIVIGLOB/NVP trial was associated with increased risk of serious gastroenteritis among HIV-exposed uninfected infants when compared with later breastfeeding cessation in the HIVNET 012 trial. Testing interventions, which could decrease HIV transmission through breastfeeding and allow safe breastfeeding into the second year of life, are urgently needed. C1 [Onyango-Makumbi, Carolyne; Bagenda, Danstan; Musoke, Philippa; Mmiro, Francis; Kateera, Brenda Asiimwe; Musisi, Maria] MU JHU CARE LTD, Makerere Univ John Hopkins Univ Res Collaborat, Kampala, Uganda. [Bagenda, Danstan] Makerere Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Kampala, Uganda. [Mwatha, Antony] Fred Hutchinson Canc Res Ctr, SCHARP, Seattle, WA 98104 USA. [Omer, Saad B.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA. [Musoke, Philippa] Makerere Univ, Sch Med, Dept Pediat & Child Hlth, Kampala, Uganda. [Zwerski, Sheryl L.] NIAID, Div Aids, NIH, Rockville, MD USA. [Fowler, Mary Glenn; Jackson, J. Brooks; Guay, Laura A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Onyango-Makumbi, C (reprint author), MU JHU CARE LTD, Makerere Univ John Hopkins Univ Res Collaborat, POB 23491, Kampala, Uganda. EM carolonyango@mujhu.org RI Omer, Saad/K-1182-2012 OI Omer, Saad/0000-0002-5383-3474 FU NIAID NIH HHS [UO1 AI048054, N01 AI035173, N01 AI045200, N01-AI-35173- 417, R01 AI034235, R01 AI034235-06, R01 AI069350, R01-AI34235, U01 AI038576, U01 AI038576-06, U01 AI048054, U01 AI048054-01, U01 AI068617-03, U01 AI068617-04, U01 AI068632, U01 AI068632-01, U01 AI068632-03, U01 AI069530, U01 AI069530-01, UO1 AI038576, UO1 AI068617, UO1 AI69530] NR 46 TC 31 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2010 VL 53 IS 1 BP 20 EP 27 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 538KG UT WOS:000273182400005 PM 19779355 ER PT J AU Brady, MT Oleske, JM Williams, PL Elgie, C Mofenson, LM Dankner, WM Van Dyke, RB AF Brady, Michael T. Oleske, James M. Williams, Paige L. Elgie, Carol Mofenson, Lynne M. Dankner, Wayne M. Van Dyke, Russell B. CA Pediat AIDS Clinical Trials Grp219 TI Declines in Mortality Rates and Changes in Causes of Death in HIV-1-Infected Children During the HAART Era SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE pediatric HIV infection; highly active antiretroval therapy; mortality ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; PEDIATRIC HIV-INFECTION; UNITED-STATES; ADOLESCENTS; SURVIVAL; INFANTS; NEPHROPATHY; MORBIDITY; IRELAND AB Context: Introduction of highly active antiretroviral therapy has significantly decreased mortality in HIV-1-infected adults and children. Although an increase in non-HIV-related mortality has been noted in adults, data in children are limited. Objectives: To evaluate changes in causes and risk factors for death among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C. Design, Setting, and Participants: Multicenter, prospective cohort study designed to evaluate long-term outcomes in HIV-1-exposed and infected US children. There were 3553 HIV-1-infected children enrolled and followed up between April 1993 and December 2006, with primary cause of mortality identified in the 298 observed deaths. Main Outcome Measures: Mortality rates per 100 child-years overall and by demographic factors; survival estimates by birth cohort; and hazard ratios for mortality by various demographic, health, and antiretroviral treatment factors were determined. Results: Among 3553 HIV-1-infected children followed up for a median of 5.3 years, 298 deaths occurred. Death rates significantly decreased between 1994 and 2000, from 7.2 to 0.8 per 100 person-years, and remained relatively stable through 2006. After adjustment for other covariates, increased risk of death was identified for those with low CD4 and AIDS-defining illness at entry. Decreased risks of mortality were identified for later birth cohorts, and for time-dependent initiation of highly active antiretroviral therapy (hazard ratio 0.54, P < 0.001). The most common causes of death were "End-stage AIDS" (N = 48, 16%) and pneumonia (N = 41, 14%). The proportion of deaths due to opportunistic infections (OIs) declined from 37% in 1994-1996 to 24% after 2000. All 01 mortality declined during the study period. However, a greater decline was noted for deaths due to Mycobacterium avium complex and cryptosporidium. Deaths from "End-stage AIDS," sepsis and renal failure increased. Conclusions: overall death rates declined from 1993 to 2000 but have since stabilized at rates about 30 times higher than for the general US pediatric population. Deaths due to OIs have declined, but non-AIDS-defining infections and multiorgan failure remain major causes of mortality in HIV-1-infected children. C1 [Brady, Michael T.] Nationwide Childrens Hosp, Columbus, OH USA. [Oleske, James M.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Brady, Michael T.] Ohio State Univ, Columbus, OH 43210 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, CBAR, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Elgie, Carol] Frontier Sci Technol & Res Fdn, Amherst, NY USA. [Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Dankner, Wayne M.] Parexel Int, Durham, NC USA. [Dankner, Wayne M.] Duke Univ, Med Ctr, Durham, NC USA. [Van Dyke, Russell B.] Tulane Univ, New Orleans, LA 70118 USA. RP Brady, MT (reprint author), 700 Childrens Dr,AB7048, Columbus, OH 43025 USA. EM michael.Brady@nationalwidechildrens.org RI Oleske, James/C-1951-2016; OI Oleske, James/0000-0003-2305-5605; Mofenson, Lynne/0000-0002-2818-9808 FU NICHD NIH HHS [N01 HD033162] NR 29 TC 114 Z9 118 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2010 VL 53 IS 1 BP 86 EP 94 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 538KG UT WOS:000273182400013 PM 20035164 ER PT J AU Jin, X Smith, K Chen, RY Ding, GW Yao, Y Wang, HB Qian, HZ Chang, DF Wang, GX Wang, N AF Jin, Xia Smith, Kumi Chen, Ray Y. Ding, Guowei Yao, Yan Wang, Haibo Qian, Han-Zhu Chang, Dongfang Wang, Guixiang Wang, Ning TI HIV Prevalence and Risk Behaviors Among Male Clients of Female Sex Workers in Yunnan, China SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE China; clients of female sex workers; commercial sex; condom use; HIV ID INFECTION; TRANSMISSION; PREDICTORS; PROVINCE AB Objectives: To assess the prevalence and risk factors of HIV among male clients of female sex workers (FSWs) in China. Methods: Convenience sampling methods were used to recruit 315 clients using FSW-client and client-client networks. Subjects provided information on sociodemographic characteristics and sexual and drug behavior patterns. Blood samples were collected for HIV testing and Urine samples for opiate testing. Results: Overall HIV prevalence was 6.0%; among drug users, it was 30.8%. 33.7% of respondents reported that they always use condoms in commercial sex and 63.5% that they used a condom in the last commercial sex episode. Drug use (OR: 6.1; 95% CI: 1.7 to 21.4) and lack of a regular sexual partner (OR: 6.3; 95% CI: 1.8 to 21.9) were significantly associated with HIV infection, Conclusions: Clients of FSWs serve as potential bridges for HIV transmission from the high-risk FSWs to the low-risk general population, making them a key target for intervention. High HIV prevalence rates among clients in Kaiyuan is particularly alarming given their risk behavior patterns including high rates of partner exchange, low condom use rates, and drug-using behaviors. Innovative interventions are needed to reduce the risk of HIV among clients and reduce the bridge of transmission to the general population. C1 [Jin, Xia; Smith, Kumi; Ding, Guowei; Wang, Haibo; Wang, Ning] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS Sexually Transmitted Dis Control &, Dept Epidemiol, Beijing 100050, Peoples R China. [Chen, Ray Y.] US Embassy, Off Global Res, NIAID, US Natl Inst Hlth, Beijing, Peoples R China. [Yao, Yan] Jilin Univ, Dept Epidemiol & Med Stat, Sch Publ Hlth, Changchun 130023, Jilin Province, Peoples R China. [Qian, Han-Zhu] Vanderbilt Univ, Dept Med, Inst Global Hlth, Nashville, TN USA. [Chang, Dongfang; Wang, Guixiang] Kaiyuan City Ctr Dis Control & Prevent, Kaiyuan, Yunnan Province, Peoples R China. RP Wang, N (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS Sexually Transmitted Dis Control &, Dept Epidemiol, 27 Nanwei Rd, Beijing 100050, Peoples R China. EM wangnbj@163.com OI Chen, Ray/0000-0001-6344-1442 FU US National Institutes of Health/National Institute of Allergy and Infectious Diseases [U19 AI51915] FX The China Integrated Program for Research on AIDS was funded by US National Institutes of Health/National Institute of Allergy and Infectious Diseases (U19 AI51915). NR 18 TC 27 Z9 30 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2010 VL 53 IS 1 BP 131 EP 135 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 538KG UT WOS:000273182400020 PM 19730110 ER PT J AU Brogly, SB Foca, M Deville, JG Mirochnick, M Scott, GB Mofenson, LM Read, JS Viani, RM Burchett, SK Cooper, ER Browning, R Shapiro, DE AF Brogly, Susan B. Foca, Marc Deville, Jaime G. Mirochnick, Mark Scott, Gwendolyn B. Mofenson, Lynne M. Read, Jennifer S. Viani, Rolando M. Burchett, Sandra K. Cooper, Ellen R. Browning, Renee Shapiro, David E. TI Potential Confounding of the Association Between Exposure to Nucleoside Analogues and Mitochondrial Dysfunction in HIV-Uninfected and Indeterminate Infants SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID ANTIRETROVIRAL THERAPY; CHILDREN; MONKEYS C1 [Brogly, Susan B.; Shapiro, David E.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Brogly, Susan B.; Shapiro, David E.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Foca, Marc] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Deville, Jaime G.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Mirochnick, Mark] Boston Univ, Dept Pediat, Boston, MA 02215 USA. [Scott, Gwendolyn B.] Univ Miami, Dept Pediat, Miller Sch Med, Miami, FL 33152 USA. [Mofenson, Lynne M.; Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. [Viani, Rolando M.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. [Cooper, Ellen R.] Boston Univ, Sch Med, Dept Pediat Infect Dis, Boston, MA 02118 USA. [Burchett, Sandra K.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Browning, Renee] NIAID, Henry M Jackson Fdn, Div Aids, NIH, Bethesda, MD 20892 USA. RP Brogly, SB (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 665 Huntington Ave, Boston, MA 02115 USA. RI Viani, Rolando/C-3501-2013; OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [HHSN272200800001G, HHSN272200800001C, HHSN272200800001I, HHSN272200800001O, HHSN272200800004C, HHSN272200800014C, U01 AI068616, U01 AI068616-01, U01 AI068632]; NICHD NIH HHS [HHSN267200800001C]; NIDDK NIH HHS [HHSN267200800001G] NR 12 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2010 VL 53 IS 1 BP 154 EP 157 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 538KG UT WOS:000273182400026 PM 20035168 ER PT J AU Hassan, MA Feril, LB Kudo, N Tachibana, K Kondo, T Riesz, P AF Hassan, Mariame A. Feril, Loreto B., Jr. Kudo, Nobuki Tachibana, Katsuro Kondo, Takashi Riesz, Peter TI The Sonochemical and Biological Effects of Three Clinically-Used Contrast Agents SO JAPANESE JOURNAL OF APPLIED PHYSICS LA English DT Article; Proceedings Paper CT 30TH SYMPOSIUM ON ULTRASONIC ELECTRONICS CY NOV 18-20, 2009 CL KYOTO, JAPAN ID FREE-RADICAL FORMATION; ULTRASOUND-INDUCED APOPTOSIS; LOW-INTENSITY ULTRASOUND; IN-VITRO; THERAPEUTIC APPLICATION; INDUCED HEMOLYSIS; GENE-EXPRESSION; HIGH CELL; MICROBUBBLES; ENHANCEMENT AB The encapsulation of gas bubbles has resulted in improved stability and added a binding capacity to shells for ultrasound-guided targeted delivery. However, this has also changed the physical and acoustical properties of the final formulation. In this study, we have evaluated three clinically-used contrast agents of different compositions, namely, Levovist, Sonazoid, and SonoVue, with respect to their sonochemical and biological effects at different concentrations. The results showed that both shell elasticity and reactivity played a role in modulating both effects influencing the extent of ultrasound-induced free-radical formation. Microbubbles with elastic shells were found to be more capable of inducing delayed symptoms of cell killing, whereas the combined use of chemically reactive robust shells and high-density gases, such as perfluorocarbons, could exert a protective effect on cells. These conclusions offer new perspectives on how microbubbles interact with biological systems and might be useful in tailoring novel microbubbles in the future. (C) 2010 The Japan Society of Applied Physics C1 [Hassan, Mariame A.; Kondo, Takashi] Toyama Univ, Dept Radiol Sci, Grad Sch Med & Pharmaceut Sci, Toyama 9300194, Japan. [Hassan, Mariame A.; Tachibana, Katsuro] Cairo Univ, Dept Pharmaceut & Ind Pharm, Fac Pharm, Cairo 11562, Egypt. [Feril, Loreto B., Jr.] Fukuoka Univ, Sch Med, Dept Anat, Fukuoka 8140180, Japan. [Kudo, Nobuki] Hokkaido Univ, Lab Biomed Instrumentat & Measurements, Grad Sch Informat Sci & Technol, Sapporo, Hokkaido 0600814, Japan. [Riesz, Peter] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Hassan, MA (reprint author), Toyama Univ, Dept Radiol Sci, Grad Sch Med & Pharmaceut Sci, Toyama 9300194, Japan. EM kondot@med.u-toyama.ac.jp RI Kudo, Nobuki/D-6742-2012 NR 40 TC 3 Z9 3 U1 0 U2 5 PU JAPAN SOC APPLIED PHYSICS PI TOKYO PA KUDAN-KITA BUILDING 5TH FLOOR, 1-12-3 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0021-4922 J9 JPN J APPL PHYS JI Jpn. J. Appl. Phys. PY 2010 VL 49 IS 7 AR 07HF23 DI 10.1143/JJAP.49.07HF23 PN 2 PG 6 WC Physics, Applied SC Physics GA 631XK UT WOS:000280383800107 ER PT J AU Zhang, MJ Katanoda, K AF Zhang, Ming-Ji Katanoda, Kota TI Comparison of Time Trends in Uterus Cancer and Cervix Uteri Cancer Mortality (1990-2006) in the World, from the WHO Mortality Database SO JAPANESE JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 [Zhang, Ming-Ji] Natl Canc Ctr, Ctr Canc Control & Informat Serv, Canc Informat Serv, Bethesda, MD 20892 USA. Natl Canc Ctr, Ctr Canc Control & Informat Serv, Surveillance Div, Bethesda, MD 20892 USA. RP Zhang, MJ (reprint author), Natl Canc Ctr, Ctr Canc Control & Informat Serv, Canc Informat Serv, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0368-2811 J9 JPN J CLIN ONCOL JI Jpn. J. Clin. Oncol. PD JAN PY 2010 VL 40 IS 1 BP 98 EP 99 DI 10.1093/jjco/hyp180 PG 2 WC Oncology SC Oncology GA 539BH UT WOS:000273227900018 PM 20044391 ER PT J AU Bowers, B Hasni, S Gruber, BL AF Bowers, Brian Hasni, Sarfaraz Gruber, Barry L. TI Sarcoidosis in World Trade Center Rescue Workers Presenting With Rheumatologic Manifestations SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article ID PULMONARY-DISEASE; CENTER SITE; FIREFIGHTERS; COLLAPSE AB The health consequences of the World Trade Center collapse are unknown, but likely to be significant and may take years to fully appreciate. Sarcoidosis is a multisystem inflammatory disorder of unknown etiology characterized pathologically by noncaseating granulomas, Inciting events, such as infectious agents or possible environmental exposures, have been postulated as the Source of antigen exposure initiating an inflammatory cascade. We describe 2 cases of sarcoidosis in rescue workers with significant exposure from the World Trade Center collapse, who presented with extrapulmonary rheumatologic manifestations. Our first case involved a 33-year-old white New York City man detective found to have sarcoidosis following an evaluation of diffuse joint pain. The second case involved a 40-year-old African American man, New York City officer, who presented With uveitis, and was subsequently diagnosed with sarcoidosis. These 2 cases extend the spectrum of disorders resulting from the World Trade Center disaster and illustrate the need for clinicians to be aware of the diverse presentations of sarcoidosis in this patient population. C1 [Bowers, Brian; Gruber, Barry L.] New York Coll Osteopath Med, Dept Med, Old Westbury, NY 11568 USA. [Hasni, Sarfaraz] NIAMSD, Bethesda, MD 20892 USA. RP Bowers, B (reprint author), New York Coll Osteopath Med, Dept Med, POB 8000,Northern Blvd, Old Westbury, NY 11568 USA. EM BBower01@NYIT.edu NR 16 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD JAN PY 2010 VL 16 IS 1 BP 26 EP 27 DI 10.1097/RHU.0b013e3181c78856 PG 2 WC Rheumatology SC Rheumatology GA 546BN UT WOS:000273782300008 PM 20051752 ER PT J AU Calsyn, DA Campbell, ANC Crits-Christoph, P Doyle, SR Tross, S Hatch-Maillette, MA Mandler, R AF Calsyn, Donald A. Campbell, Aimee N. C. Crits-Christoph, Paul Doyle, Suzanne R. Tross, Susan Hatch-Maillette, Mary A. Mandler, Raul TI Men in Methadone Maintenance versus Psychosocial Outpatient Treatment: Differences in Sexual Risk Behaviors and Intervention Effectiveness from a Multisite HIV Prevention Intervention Trial SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE HIV prevention; substance abuse treatment modality; behavioral intervention; sexual risk reduction ID DRUG-ABUSE TREATMENT; PRACTICAL CLINICAL-TRIALS; TREATMENT RETENTION; TREATMENT PROGRAMS; DECISION-MAKING; REDUCTION; HEROIN; DATOS; METAANALYSIS; INFECTION AB The effectiveness of the Real Men Are Safe (REMAS) HIV prevention intervention was examined as a function of treatment program modality. REMAS was associated with significantly larger decreases in unprotected sexual occasions than an HIV education control condition in both treatment modalities. REMAS had superior effectiveness for reducing unprotected sexual occasions in the psychosocial outpatient compared to methadone. At the 6-month follow-up, the adjusted mean change for REMAS completers in psychosocial outpatient (M= 6.4, d= 0.38) was greater than for REMAS completers in methadone programs (M= 2.3, d= 0.25). Reasons for why REMAS appears to be especially effective in psychosocial outpatient programs are explored. C1 [Calsyn, Donald A.; Hatch-Maillette, Mary A.] Univ Washington Alcohol & Drug Abuse Inst, Univ Washington Sch Med, Seattle, WA USA. [Campbell, Aimee N. C.] New York State Psychiat Inst & Hosp, Substance Abuse Div, New York, NY USA. [Crits-Christoph, Paul] Univ Pennsylvania Sch Med, Philadelphia, PA USA. [Tross, Susan] New York State Psychiat Inst & Hosp, Substance Abuse Div, New York, NY USA. [Mandler, Raul] Natl Inst Drug Abuse, Ctr Clin Trials Network, Rockville, MD USA. [Calsyn, Donald A.; Doyle, Suzanne R.; Hatch-Maillette, Mary A.] Univ Washington, Alcohol & Drug Abuse Inst, Seattle, WA 98105 USA. [Calsyn, Donald A.; Hatch-Maillette, Mary A.] Univ Washington, Sch Med, Seattle, WA 98105 USA. [Campbell, Aimee N. C.; Tross, Susan] New York State Psychiat Inst & Hosp, Subst Abuse Div, New York, NY 10032 USA. [Crits-Christoph, Paul] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Tross, Susan] Columbia Univ, New York, NY USA. [Mandler, Raul] Natl Inst Drug Abuse, Ctr Clin Trials Network, Rockville, MD USA. RP Calsyn, DA (reprint author), Univ Washington, Alcohol & Drug Abuse Inst, 1107 NE 45th St,Suite 120, Seattle, WA 98105 USA. EM calsyn@u.washington.edu FU NIDA NIH HHS [U10 DA13045, R33 DA027521, U10 DA013035, U10 DA013035-08, U10 DA013038, U10 DA013038-10, U10 DA013043, U10 DA013043-10, U10 DA013045, U10 DA013045-10, U10 DA013711, U10 DA013711-05, U10 DA013714, U10 DA013714-08, U10 DA013727, U10 DA013727-10, U10 DA013732, U10 DA013732-10, U10 DA015815, U10 DA015815-08, U10 DA015833, U10 DA015833-03, U10 DA13035, U10 DA13038, U10 DA13043, U10 DA13711, U10 DA13714, U10 DA13727, U10 DA13732, U10 DA15815, U10 DA15833, UG1 DA015815] NR 42 TC 1 Z9 1 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2010 VL 29 IS 3 BP 370 EP 382 AR PII 924379540 DI 10.1080/10550887.2010.489451 PG 13 WC Substance Abuse SC Substance Abuse GA 626JY UT WOS:000279963500012 PM 20635286 ER PT J AU Felsen, UR Fishbein, DA Litwin, AH AF Felsen, Uriel R. Fishbein, Dawn A. Litwin, Alain H. TI Low Rates of Hepatitis A and B Vaccination in Patients with Chronic Hepatitis C at an Urban Methadone Maintenance Program SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE Hepatitis; vaccination; methadone ID INJECTION-DRUG USERS; VIRUS-INFECTION; MISSED OPPORTUNITIES; SUPERINFECTION; CARE AB Patients with chronic hepatitis C virus (HCV) are at increased risk for complications of liver disease if they become infected with the hepatitis A (HAV) or hepatitis B (HBV) viruses. The authors examined the rates of testing for HAV, HBV, and HCV, as well as rates of vaccination against HAV and HBV in patients with chronic HCV in a random sample (N = 207) of medical records of patients enrolled in a methadone maintenance program. Almost all patients reviewed were tested for HAV, HBV, and HCV. Of the 111 patients with chronic HCV, 53 (48.6%) and 68 (63%) lacked immunity to HAV and HBV, respectively. Of those lacking immunity, 29 (54.7%) and 2 (2.9%) were vaccinated for HAV and HBV, respectively. Despite high rates of testing for HAV, HBV, and HCV at a methadone maintenance program, approximately half of those with chronic HCV eligible for the HAV vaccine received it, and few of those eligible for HBV vaccine received it. C1 [Felsen, Uriel R.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Fishbein, Dawn A.] NCI, SAIC Frederick Inc, Clin Monitoring Res Program, Support Crit Care Med Dept,NIH, Frederick, MD 21701 USA. [Fishbein, Dawn A.] NCI, SAIC Frederick Inc, Clin Monitoring Res Program, Support Crit Care Med Dept,NIH, Washington, DC USA. RP Felsen, UR (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, 3332 Rochambeau Ave, Bronx, NY 10467 USA. EM ufelsen@montefiore.org FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; NIDA NIH HHS [K23 DA018623]; PHS HHS [HHSN261200800001E] NR 16 TC 3 Z9 3 U1 1 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2010 VL 29 IS 4 BP 461 EP 465 AR PII 927634582 DI 10.1080/10550887.2010.509281 PG 5 WC Substance Abuse SC Substance Abuse GA 659RI UT WOS:000282584200006 PM 20924882 ER PT J AU Borges, G Benjet, C Medina-Mora, ME Orozco, R Familiar, I Nock, MK Wang, PS AF Borges, Guilherme Benjet, Corina Elena Medina-Mora, Maria Orozco, Ricardo Familiar, Itziar Nock, Matthew K. Wang, Philip S. TI Service use among Mexico City adolescents with suicidality SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Suicide; Risk factors; Adolescence; Service use; Mexico ID NATIONAL COMORBIDITY SURVEY; MENTAL-HEALTH SURVEY; RISK-FACTORS; CARE CONTACTS; DRUG-USE; BEHAVIOR; PREVALENCE; IDEATION; LIFETIME; YOUTH AB Background: We report the lifetime and 12-month prevalence and associations of mental health treatment among Mexican adolescents with suicide-related outcomes (SROs; including ideation, plans, gestures and attempts). Methods: A representative multistage probability household survey of 3005 adolescents aged 12 to 17 years residing in the Mexico City Metropolitan Area was carried out in 2005. Discrete-time survival analyses were used to assess the relationships between SROs and receiving treatment for emotional, alcohol, or drug problems. Results: The prevalence of lifetime service use among respondents with SROs was 35% for those with ideation only, 44% for those with ideation and plan, 49% for those with gesture and 50% for those with attempt; the prevalence of 12-month service use was 10%, 24%, 6% and 21%, respectively. Timing between onset of SRO and receiving treatment for emotional, alcohol, or drug problems showed that about 50% of adolescents will have contact with a service provider before developing any SRO. Healthcare professionals were the most likely to be consulted, followed by school-based programs. Limitations: This survey was limited to adolescents living in one of the largest metropolitan areas in the world and the analyses used data on retrospectively reported ages of onset that are subject to recall errors. Conclusions: Most suicidal adolescents do not receive treatment, and many adolescents develop their suicidality in spite of prior contacts with service providers. Interventions to increase treatment, prevention, and monitoring are sorely needed for this vulnerable population. (C) 2009 Elsevier B.V. All rights reserved. C1 [Borges, Guilherme; Benjet, Corina; Elena Medina-Mora, Maria; Orozco, Ricardo] Inst Nacl Psiquiatria, Mexico City 10610, DF, Mexico. [Familiar, Itziar] Mexican Hlth Fdn, Mexico City, DF, Mexico. [Wang, Philip S.] NIMH, Bethesda, MD 20892 USA. [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Borges, G (reprint author), Inst Nacl Psiquiatria, Calzada Mexico Xochimilco 101-Col San Lorenzo Hui, Mexico City 10610, DF, Mexico. EM guibor@imp.edu.mx RI Benjet, Corina/D-7363-2012; OI Borges, Guilherme/0000-0002-3269-0507; Benjet, Corina/0000-0002-4569-6094 FU American Foundation for Suicide Prevention-Standard Research; National Council on Science and Technology [CONACYT-SEP-SSEDF-2003-CO1-22]; National Institute of Psychiatry Ramon de la Fuente Muniz [DIES-4845]; United States National Institute of Mental Health [R01MH070884, R01MH077883]; John D. and Catherine T. MacArthur Foundation; Pfizer Foundation; US Public Health Service [R13-MH066849, R01-MH069864, R01 DA016558]; Fogarty International Center [FIRCA R01-TW006481]; Pan American Health Organization; Eli Lilly and Company; Ortho-McNeil Pharmaceutical, Inc.; GlaxoSmithKline; Bristol-Myers Squibb FX This work was possible by the support from American Foundation for Suicide Prevention-Standard Research Grant to Dr. Guilherme Borges. The Mexican Adolescent Mental Health Survey was supported by the National Council on Science and Technology in conjunction with the Ministry of Education (grant No. CONACYT-SEP-SSEDF-2003-CO1-22) and by the National Institute of Psychiatry Ramon de la Fuente Muniz (DIES-4845).; The survey was carried out in conjunction with the World Health Organization World Mental Health (WMH) Survey Initiative. We thank the WMH staff for assistance with instrumentation, fieldwork, and data analysis. These activities were supported by the United States National Institute of Mental Health (R01MH070884 and R01MH077883), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R01-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical, Inc., GlaxoSmithKline, and Bristol-Myers Squibb. NR 40 TC 8 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN PY 2010 VL 120 IS 1-3 BP 32 EP 39 DI 10.1016/j.jad.2009.04.008 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 547RP UT WOS:000273907100005 PM 19411113 ER PT J AU Sathyanarayana, S Basso, O Karr, CJ Lozano, P Alavanja, M Sandler, DP Hoppin, JA AF Sathyanarayana, Sheela Basso, Olga Karr, Catherine J. Lozano, Paula Alavanja, Michael Sandler, Dale P. Hoppin, Jane A. TI Maternal Pesticide Use and Birth Weight in the Agricultural Health Study SO JOURNAL OF AGROMEDICINE LA English DT Article DE Agricultural exposures; birth weight; carbaryl; pesticides; reproductive epidemiology AB Studies examining the association between maternal pesticide exposure and low birth weight yield conflicting results. The authors examined the association between maternal pesticide use and birth weight among women in the Agricultural Health Study, a large study of pesticide applicators and their spouses in Iowa and North Carolina. The authors evaluated self-reported pesticide use of 27 individual pesticides in relation to birth weight among 2246 farm women whose most recent singleton birth occurred within 5 years of enrollment (1993-1997). The authors used linear regression models adjusted for site, preterm birth, medical parity, maternal body mass index, height, and smoking. The results showed that mean infant birth weight was 3586 g (+/- 546 g), and 3% of the infants were low birth weight (< 2500 g). First-trimester pesticide-related tasks were not associated with birth weight. Ever use of the pesticide carbaryl was associated with decreased birth weight (-82 g, 95% confidence interval [CI] = -132, -31). This study thus provides limited evidence about pesticide use as a modulator of birth weight. Overall, the authors observed no associations between birth weight and pesticide-related activities during early pregnancy; however, the authors have no data on temporal specificity of individual pesticide exposures prior to or during pregnancy and therefore cannot draw conclusions related to these exposure windows. Given the widespread exposure to pesticide products, additional evaluation of maternal pregnancy exposures at specific time windows and subsequent birth outcomes is warranted. C1 [Sathyanarayana, Sheela; Karr, Catherine J.; Lozano, Paula] Univ Washington, Dept Pediat, Seattle, WA 98101 USA. [Basso, Olga; Sandler, Dale P.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Karr, Catherine J.] Univ Washington, Dept Occupat & Environm Hlth Sci, Seattle, WA 98101 USA. [Alavanja, Michael] NCI, NIH, DHHS, Bethesda, MD 20892 USA. RP Sathyanarayana, S (reprint author), Univ Washington, Dept Pediat, CCHBD, Seattle Childrens Hosp, 1100 Olive Way,Suite 500,M-S 8-1,Box 359300, Seattle, WA 98101 USA. EM sheela.sathyanarayana@seattlechildrens.org OI Sandler, Dale/0000-0002-6776-0018 FU NIH, National Institute of Environmental Health Sciences [Z01-ES049030]; National Cancer Institute [Z01-CP010119] FX This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049030) and National Cancer Institute (Z01-CP010119). All authors have no competing financial interests to disclose. NR 32 TC 16 Z9 17 U1 3 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-924X J9 J AGROMEDICINE JI J. Agromedicine PY 2010 VL 15 IS 2 BP 127 EP 136 DI 10.1080/10599241003622699 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V21QT UT WOS:000208222800012 PM 20407994 ER PT J AU Gruenberg, DA Anover-Sombke, S Gern, JE Holland, SM Rosenzweig, SD Torgerson, TR Seroogy, CM AF Gruenberg, David A. Anover-Sombke, Stephanie Gern, James E. Holland, Steven M. Rosenzweig, Sergio D. Torgerson, Troy R. Seroogy, Christine M. TI Atypical presentation of IL-12 receptor beta 1 deficiency with pneumococcal sepsis and disseminated nontuberculous mycobacterial infection in a 19-month-old girl born to nonconsanguineous US residents SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 [Gruenberg, David A.; Gern, James E.; Seroogy, Christine M.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Anover-Sombke, Stephanie; Torgerson, Troy R.] Univ Washington, Seattle, WA 98195 USA. [Anover-Sombke, Stephanie; Torgerson, Troy R.] Seattle Childrens Res Inst, Seattle, WA USA. [Holland, Steven M.; Rosenzweig, Sergio D.] NIH, Bethesda, MD 20892 USA. RP Gruenberg, DA (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM cmseroogy@wisc.edu FU Intramural NIH HHS [Z99 AI999999] NR 7 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2010 VL 125 IS 1 BP 264 EP 265 DI 10.1016/j.jaci.2009.07.061 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 544MG UT WOS:000273660500033 PM 19910038 ER PT J AU Liu, D Pitta, M Lee, JH Ray, B Lahiri, DK Furukawa, K Mughal, M Jiang, HY Villarreal, J Cutler, RG Greig, NH Mattson, MP AF Liu, Dong Pitta, Michael Lee, Jong-Hwan Ray, Balmiki Lahiri, Debomoy K. Furukawa, Katsutoshi Mughal, Mohamed Jiang, Haiyang Villarreal, Julissa Cutler, Roy G. Greig, Nigel H. Mattson, Mark P. TI The K-ATP Channel Activator Diazoxide Ameliorates Amyloid-beta and Tau Pathologies and Improves Memory in the 3xTgAD Mouse Model of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE 3xTgAD; calcium; cerebral blood flow; diazoxide; excitotoxicity; hippocampus; hyperpolerization; learning and memory; K-ATP channels ID DEPENDENT POTASSIUM CHANNELS; HIPPOCAMPAL-NEURONS; ENERGY-METABOLISM; PRECURSOR PROTEIN; TRANSGENIC MICE; A-BETA; CYTOSKELETAL PATHOLOGY; BEHAVIORAL DEFICITS; IN-VIVO; MITOCHONDRIAL AB Compromised cellular energy metabolism, cerebral hypoperfusion, and neuronal calcium dysregulation are involved in the pathological process of Alzheimer's disease (AD). ATP-sensitive potassium (K-ATP) channels in plasma membrane and inner mitochondrial membrane play important roles in modulating neuronal excitability, cell survival, and cerebral vascular tone. To investigate the therapeutic potential of drugs that activate K-ATP channels in AD, we first characterized the effects of the K-ATP channel opener diazoxide on cultured neurons, and then determined its ability to modify the disease process in the 3xTgAD mouse model of AD. Plasma and mitochondrial membrane potentials, cell excitability, intracellular Ca2+ levels and bioenergetics were measured in cultured cerebral cortical neurons exposed to diazoxide. Diazoxide hyperpolarized neurons, reduced the frequency of action potentials, attenuated Ca2+ influx through NMDA receptor channels, and reduced oxidative stress. 3xTgAD mice treated with diazoxide for 8 months exhibited improved performance in a learning and memory test, reduced levels of anxiety, decreased accumulation of A beta oligomers and hyperphosphorylated tau in the cortex and hippocampus, and increased cerebral blood flow. Our findings show that diazoxide can ameliorate molecular, cytopathological, and behavioral alterations in a mouse model of AD suggesting a therapeutic potential for drugs that activate K-ATP channels in the treatment of AD. C1 [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Biomed Res Ctr, Baltimore, MD 21224 USA. [Lee, Jong-Hwan] Konkuk Univ, Coll Vet Med, Dept Anat, Seoul, South Korea. [Ray, Balmiki; Lahiri, Debomoy K.] Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN USA. [Villarreal, Julissa] NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Lee, Jong Hwan/D-8530-2011; Ray, Balmiki/F-5445-2011; Mattson, Mark/F-6038-2012 FU National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institute on Aging. NR 63 TC 47 Z9 49 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2010 VL 22 IS 2 BP 443 EP 457 DI 10.3233/JAD-2010-101017 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 681JW UT WOS:000284309200008 PM 20847430 ER PT J AU Thambisetty, M Tripaldi, R Riddoch-Contreras, J Hye, A An, Y Campbell, J Sojkova, J Kinsey, A Lynham, S Zhou, Y Ferrucci, L Wong, DF Lovestone, S Resnick, SM AF Thambisetty, Madhav Tripaldi, Romina Riddoch-Contreras, Joanna Hye, Abdul An, Yang Campbell, James Sojkova, Jitka Kinsey, Anna Lynham, Steven Zhou, Yun Ferrucci, Luigi Wong, Dean F. Lovestone, Simon Resnick, Susan M. TI Proteome-Based Plasma Markers of Brain Amyloid-beta Deposition in Non-Demented Older Individuals SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta; biomarker; brain; plasma; proteomics ID PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; IN-VIVO; A-BETA; COGNITIVE-DECLINE; GENETIC RISK; APOE; DIAGNOSIS; METABOLISM AB Blood-based markers reflecting core pathological features of Alzheimer's disease (AD) in pre-symptomatic individuals are likely to accelerate the development of disease-modifying treatments. Our aim was to discover plasma proteins associated with brain amyloid-beta (A beta) burden in non-demented older individuals. We performed discovery-phase experiments using two dimensional gel electrophoresis (2DGE) and mass spectrometry-based proteomic analysis of plasma in combination with (11)C-PiB PET imaging of the brain in samples collected 10 years prior to the PET scans. Confirmatory studies used ELISA assays in a separate set of blood samples obtained within a year of the PET scans. We observed that a panel of 18 2DGE plasma protein spots effectively discriminated between individuals with high and low brain A beta. Mass spectrometry identified these proteins, many of which have established roles in A beta clearance, including a strong signal from apolipoprotein-E (ApoE). In validation-phase studies, we observed a strong association between plasma ApoE concentration and A beta burden in the medial temporal lobe. Targeted voxel-based analysis localized this association to the hippocampus and entorhinal cortex. APOE epsilon 4 carriers also showed greater A beta levels in several brain regions relative to epsilon 4 non-carriers. These results suggest that both peripheral concentration of ApoE protein and APOE genotype are related to early neuropathological changes in brain regions vulnerable to AD pathology even in the non-demented elderly. Our strategy combining proteomics with in vivo brain amyloid imaging holds promise for the discovery of biologically relevant peripheral markers in those at risk for AD. C1 [Thambisetty, Madhav] NIA, NIH, Baltimore, MD 21224 USA. [Tripaldi, Romina; Riddoch-Contreras, Joanna; Hye, Abdul; Kinsey, Anna; Lynham, Steven; Lovestone, Simon] Inst Psychiat, London, England. [Campbell, James] Proteome Sci Plc, London, England. [Zhou, Yun; Wong, Dean F.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Thambisetty, M (reprint author), NIA, NIH, Room 4B-311,251 Bayview Blvd, Baltimore, MD 21224 USA. EM thambisettym@mail.nih.gov OI Kinsey, Anna/0000-0001-8987-5353 FU NIH, National Institute on Aging; National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust(SLaM) [N01-AG-3-2124]; Institute of Psychiatry, King's College London; Med-Star Research Institute FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging and by Research and Development Contract N01-AG-3-2124 together with funding from the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust(SLaM) and Institute of Psychiatry, King's College London. Partial support was also through a R&D contract with Med-Star Research Institute. We are grateful to the BLSA participants and neuroimaging staff for their dedication to these studies and the staff of the Johns Hopkins PET facility for their assistance. NR 51 TC 33 Z9 33 U1 1 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2010 VL 22 IS 4 BP 1099 EP 1109 DI 10.3233/JAD-2010-101350 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 706AS UT WOS:000286185300006 PM 20930274 ER PT J AU Winblad, B Giacobini, E Frolich, L Friedhoff, LT Bruinsma, G Becker, RE Greig, NH AF Winblad, Bengt Giacobini, Ezio Froelich, Lutz Friedhoff, Lawrence T. Bruinsma, Gosse Becker, Robert E. Greig, Nigel H. TI Phenserine Efficacy in Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Acetylcholinesterase; Alzheimer's disease; Alzheimer clinical trial; amyloid-beta peptide; amyloid-beta protein precursor; cholinesterase inhibitor; phenserine ID DRUG DEVELOPMENT; CLINICAL-TRIALS; PROTEIN; MANAGEMENT; PRECURSOR; DEMENTIA; INHIBITION; MECHANISMS; THERAPIES; DONEPEZIL AB To gather preliminary evidence in Alzheimer's disease (AD) for the efficacy of phenserine, a non-competitive acetylcholinesterase inhibitor that has independent modulatory effects on amyloid-beta generation, a 12-week comparison of patients receiving phenserine (10 and 15 mg BID) or placebo was conducted under double-blind conditions. Patients who completed 12 weeks of the double-blind before others were continued in the double-blind to determine longer-term treatment effects. At 12 weeks, mean ADAS-cog (AD assessment scale-cognitive) changes from baseline were -2.5 and -1.9 for high-dose phenserine (n = 83) and placebo (n = 81) groups, respectively, a non-statistically significant improvement for the high-dose phenserine group relative to placebo. CIBIC+ (clinician's interview based impression of change + caregiver's input) values for the high-dose and placebo groups were similar at 12 weeks. For patients who received more than 12 weeks of therapy, the ADAS-cog changes were -3.18 and -0.66 for the high-dose phenserine (n = 52) and placebo (n = 63) groups, respectively, a difference achieving statistical significance (p = 0.0286). After 12 weeks, CIBIC+ values were 3.59 and 3.95 for the high-dose (n = 54) and placebo (n = 66) groups respectively (p = 0.0568). These results from this short-term study are consistent with phenserine potentially benefiting mild to moderate Alzheimer's disease symptomatically but do not address possible amyloid metabolic mediated effects on disease processes in AD. C1 [Becker, Robert E.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Winblad, Bengt] Karolinska Inst, Alzheimers Dis Res Ctr, Dept Neurobiol, Care Sci & Soc, Stockholm, Sweden. [Giacobini, Ezio] Univ Geneva, Dept Rehabil & Geriatr, Sch Med, Univ Hosp Geneva, Thonex Geneva, Switzerland. [Froelich, Lutz] Univ Heidelberg, Dept Geriatr Psychiat, Cent Inst Mental Hlth, Med Fac Mannheim, Heidelberg, Germany. [Friedhoff, Lawrence T.] Pharmaceut Special Projects Grp LLC, River Vale, NJ USA. [Bruinsma, Gosse] Ciurem Pharma BV, Leiden, Netherlands. [Becker, Robert E.] Aristea Translat Med Corp, Freeport, TX USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. EM Greign@mail.nih.gov FU National Institute on Aging, NIH; Axonyx, Inc., New York, NY, USA FX The authors thank Dr. David Fleet ( Data Magik Ltd. Salisbury, United Kingdom) for statistical analyses. Nigel Greig is supported by the Intramural Research Program of the National Institute on Aging, NIH. The described clinical research was wholly financed by Axonyx, Inc., New York, NY, USA. Gosse Bruinsma was formerly employed by Axonyx, Inc. NR 53 TC 23 Z9 25 U1 4 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2010 VL 22 IS 4 BP 1201 EP 1208 DI 10.3233/JAD-2010-101311 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 706AS UT WOS:000286185300014 PM 20930279 ER PT J AU Prakasam, A Anusuyadevi, M Ablonczy, Z Greig, NH Fauq, A Rao, KJ Pappolla, MA Sambamurti, K AF Prakasam, Annamalai Anusuyadevi, Muthuswamy Ablonczy, Zsolt Greig, Nigel H. Fauq, Abdul Rao, Kosagisharaf Jagannatha Pappolla, Miguel A. Sambamurti, Kumar TI Differential Accumulation of Secreted A beta PP Metabolites in Ocular Fluids SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Age-related macular degeneration; Alzheimer's disease; amyloid-beta protein precursor; aqueous humor; degeneration; eye vitreous humor; glaucoma; retina ID BLOOD-BRAIN-BARRIER; AMYLOID-BETA; ALZHEIMERS-DISEASE; MACULAR DEGENERATION; GAMMA-SECRETASE; MOUSE MODEL; RETINAL DEGENERATION; PROTEIN-PRECURSOR; PATHOGENESIS; DRUSEN AB Amyloid-beta (A beta) accumulates in several types of retinal degeneration and in Alzheimer's disease (AD), but its source has been unclear. We detected the neuronal 695 amino acid form of amyloid-beta protein precursor (A beta PP) in the normal retina and A beta PP751 in the retinal pigment epithelium (RPE) and anterior eye tissues. Similar to the brain, alpha- and beta-secretases cleaved A beta PP to soluble derivatives (sA beta PP) alpha or beta and membrane-bound C-terminal fragments alpha or beta in the retina and RPE. Levels of sA beta PP were particularly high in the vitreous and low in aqueous humor revealing a molecular barrier for A beta PP. In contrast, A beta(40) and A beta(42) levels were only 50% lower in the aqueous than the vitreous humor, indicating relatively barrier-free movement of A beta. These studies demonstrated a relatively high yield of A beta PP and A beta in the ocular fluids, which may serve as a trackable marker for AD. In addition, failure of free clearance from the eye may trigger retina degeneration in a manner similar to A beta-related neurodegeneration in AD. C1 [Prakasam, Annamalai; Anusuyadevi, Muthuswamy; Rao, Kosagisharaf Jagannatha; Pappolla, Miguel A.; Sambamurti, Kumar] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Ablonczy, Zsolt] Med Univ S Carolina, Storm Eye Inst, Dept Ophthalmol, Charleston, SC 29425 USA. [Greig, Nigel H.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Fauq, Abdul] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. RP Sambamurti, K (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave,BSB 403, Charleston, SC 29425 USA. EM sambak@musc.edu RI Kosagisharaf, Jagannatha Rao /N-6788-2014 OI Kosagisharaf, Jagannatha Rao /0000-0003-4290-7666 FU NIH [AG028544, AG023055]; IRP; NIA; American Health Assistance Foundation FX Supported in part by NIH grants AG028544, AG023055 (KS); NIH, IRP, NIA, (NHG); and the American Health Assistance Foundation (KS). The authors would like to thank Peter Chung, Corey Snelson, Laura Marlow, and Dr. Sharie Haugabook for some of the initial characterization studies; and Meera Parasuraman, Lucy Feingold for their help in preparing the manuscript, and Dr. Luanna Bartholomew for critical review. NR 40 TC 14 Z9 14 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2010 VL 20 IS 4 BP 1243 EP 1253 DI 10.3233/JAD-2010-100210 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 620YP UT WOS:000279539500026 PM 20413851 ER PT J AU Ferre, S AF Ferre, Sergi TI Role of the Central Ascending Neurotransmitter Systems in the Psychostimulant Effects of Caffeine SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Adenosine A(1) receptor; adenosine A(2A) receptor; ascending arousal systems; caffeine; dopaminergic system; local modules; receptor heteromers ID ADENOSINE A(2A) RECEPTORS; PEDUNCULOPONTINE TEGMENTAL NUCLEUS; BASAL FOREBRAIN NEURONS; DOPAMINE D-1 RECEPTORS; LOCUS-CERULEUS NEURONS; A(1) RECEPTORS; TUBEROMAMMILLARY NUCLEUS; MEDIATED MODULATION; HYPOCRETIN/OREXIN NEURONS; ACETYLCHOLINE-RELEASE AB Caffeine is the most consumed psychoactive drug in the world. It is a non-selective adenosine receptor antagonist that in the brain targets mainly adenosine A(1) and A(2A) receptors. The same as classical psychostimulants, caffeine produces motor-activating, reinforcing and arousing effects. This depends on the ability of caffeine to counteract multiple effects of adenosine in the central ascending neurotransmitter systems. Motor and reinforcing effects depend on the ability of caffeine to release pre- and postsynaptic brakes that adenosine imposes on the ascending dopaminergic system. By targeting A(1)-A(2A) receptor heteromers in striatal glutamatergic terminals and A(1) receptors in striatal dopaminergic terminals (presynaptic brake), caffeine induces glutamate-dependent and glutamate-independent release of dopamine. These presynaptic effects of caffeine are potentiated by the release of the postsynaptic brake imposed by antagonistic interactions in the striatal A(2A)-D(2) and A(1)-D(1) receptor heteromers. Arousing effects of caffeine depend on the blockade of multiple inhibitory mechanisms that adenosine, as an endogenous sleep-promoting substance, exerts on the multiply interconnected ascending arousal systems. Those mechanisms include a direct A(1)-receptor mediated modulation of the corticopetal basal forebrain system and an indirect A(2A)-receptor mediated modulation of the hypothalamic histaminergic and orexinergic systems. C1 NIDA, IRP, NIH, DHHS, Baltimore, MD 21224 USA. RP Ferre, S (reprint author), NIDA, IRP, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 FU National Institute on Drug Abuse FX Work supported with the intramural funds of the National Institute on Drug Abuse. NR 120 TC 40 Z9 41 U1 0 U2 14 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2010 VL 20 SU 1 BP S35 EP S49 DI 10.3233/JAD-2010-1400 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 703FL UT WOS:000285963400005 PM 20182056 ER PT J AU Rudrabhatla, P Pant, HC AF Rudrabhatla, Parvathi Pant, Harish C. TI Phosphorylation-Specific Peptidyl-Prolyl Isomerization of Neuronal Cytoskeletal Proteins by Pin1: Implications for Therapeutics in Neurodegeneration SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Alzheimer's disease; amyotrophic lateral sclerosis; neurodegeneration; neuronal cytoskeletal proteins; Pin1 ID CIS/TRANS ISOMERASE PIN1; AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID PRECURSOR PROTEIN; RNA-POLYMERASE-II; ALZHEIMERS-DISEASE; C-MYC; NEUROFILAMENT PHOSPHORYLATION; NEUROFIBRILLARY TANGLES; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN AB Pin1 [Protein Interacting with NIMA (never in mitosis A)] is a peptidyl prolyl cis-trans isomerase that isomerizes phospho-Serine/Threonine-Proline [p(S/T)-P] motifs of its target proteins. Pin1 functions in concert with proline directed kinases such as cyclin-dependent protein kinases, extracellular signal-regulated kinases, and c-Jun N-terminal kinase, and protein phosphatases such as protein phosphatase 2A (PP2A) and PP2B, in the regulation of a wide range of cellular processes including cell division, DNA damage response, and gene transcription, and in susceptibility to cancer and neurodegenerative diseases. This review focuses on the roles of Pin1 in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Frontotemporal dementia associated with parkinsonism linked to chromosome 17. Pin1 interacts with neuronal cytoskeletal proteins such as tau, amyloid-beta protein precursor, alpha-synuclein, and neurofilaments, often in association with phosphorylation events that influence their functions in the neuronal cytoskeleton. Overexpression of Pin1 reduces WT tau stability but increases P301L mutant tau stability. Pin1 associates with neurofilament H (NF-H) and modulates excitotoxic and oxidative stress induced perikaryal phosphorylation of NF-H. Pin1 mediates the neural specific apoptosis machinery. The specific inhibitors of Pin1 may have potential therapeutic implications in neurodegeneration. C1 [Pant, Harish C.] NINDS, Cytoskeletal Regulatory Prot Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Cytoskeletal Regulatory Prot Sect, Neurochem Lab, NIH, Bldg 49,Room 2A28, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov FU National Institutes of Neurological Disorders and Stroke (NINDS), National Institutes of Health FX This work is supported by intramural funding of National Institutes of Neurological Disorders and Stroke (NINDS), National Institutes of Health. NR 97 TC 21 Z9 21 U1 1 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2010 VL 19 IS 2 BP 389 EP 403 DI 10.3233/JAD-2010-1243 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 582RL UT WOS:000276616000002 PM 20110589 ER PT J AU Auffret, A Gautheron, V Mattson, MP Mariani, J Rovira, C AF Auffret, Alexandra Gautheron, Vanessa Mattson, Mark P. Mariani, Jean Rovira, Catherine TI Progressive Age-Related Impairment of the Late Long-Term Potentiation in Alzheimer's Disease Presenilin-1 Mutant Knock-in Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; Alzheimer's disease; hippocampus; long-term potentiation; presenilin 1 ID AMYLOID PRECURSOR PROTEIN; SYNAPTIC PLASTICITY; TRANSGENIC MICE; LINKED MUTATIONS; MOUSE MODEL; TRANSMISSION; HIPPOCAMPUS; MAINTENANCE; NEURONS; MEMORY AB Presenilin 1 (PS1) mutations are responsible for many early-onset familial Alzheimer's disease (FAD) cases. While increasing evidence points to impaired synaptic plasticity as an early event in AD, PS1 mutant mice exhibit a paradoxical increase in hippocampal long-term potentiation (LTP). Among PS1 mouse models, PS1 M146V mutant knock-in mice (PS1KI) are particularly interesting in that they exhibit memory impairment in spatial tasks. Here we investigated the effects of aging on two forms of LTP in PS1KI mice, the widely-studied early phase of LTP (E-LTP) and a particular form of LTP called late-LTP (L-LTP) which requires transcription and protein synthesis. L-LTP is thought to be critical for long-term memory. We found a lower L-LTP maintenance phase in PS1KI mice compared to wild type littermates at 3 months of age. As the mice age, they exhibit impairment of both the induction and maintenance phases of LTP. When E-LTP and NMDA receptor-mediated transmission were analyzed, PS1KI mice displayed an increase at 3 months compared to wild type littermates; this difference did not persist at older ages and finally decreased at 12 months. These results reveal an L-LTP decrease in PS1 mutant mice at an early stage, which occurs coincidently with a paradoxical enhancement of E-LTP. The observation of a decrease in both forms of LTP during aging supports the view that PS1KI mice are a valuable model for the study of age-dependent synaptic dysfunction and cognitive decline in AD. C1 [Auffret, Alexandra; Gautheron, Vanessa; Mariani, Jean; Rovira, Catherine] Univ Paris 06, UMR Neurobiol Proc Adaptatifs 7102, F-75005 Paris, France. [Auffret, Alexandra; Gautheron, Vanessa; Mariani, Jean; Rovira, Catherine] CNRS, UMR NPA 7102, Paris, France. [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Mariani, Jean] Hop Charles Foix, Assistance Publ Hop Paris, Unite Explorat Fonct, Ivry, France. RP Auffret, A (reprint author), Univ Paris 06, UMR Neurobiol Proc Adaptatifs 7102, 9 Quai St Bernard,Case 14, F-75005 Paris, France. EM alexandra.auffret@gmail.com RI Mattson, Mark/F-6038-2012 FU "Centre National de la Recherche Scientifique" (CNRS); Universite Pierre et Marie Curie; "Fondation de la Recherche Medicale" (France); NIH FX This work was supported by funds from "Centre National de la Recherche Scientifique" (CNRS) and Universite Pierre et Marie Curie. A. Auffret was a recipient of a fellowship from "Fondation de la Recherche Medicale" (France). We thank Dr. Ann Lohof for her critical reading of the paper. This research was also supported by the National Institute on Aging Intramural Research Program of the NIH. NR 40 TC 25 Z9 25 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2010 VL 19 IS 3 BP 1021 EP 1033 DI 10.3233/JAD-2010-1302 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 582RU UT WOS:000276617100022 PM 20157256 ER PT J AU Li, YZ Duffy, KB Ottinger, MA Ray, B Bailey, JA Holloway, HW Tweedie, D Perry, T Mattson, MP Kapogiannis, D Sambamurti, K Lahiri, DK Greig, NH AF Li, Yazhou Duffy, Kara B. Ottinger, Mary Ann Ray, Balmiki Bailey, Jason A. Holloway, Harold W. Tweedie, David Perry, TracyAnn Mattson, Mark P. Kapogiannis, Dimitrios Sambamurti, Kumar Lahiri, Debomoy K. Greig, Nigel H. TI GLP-1 Receptor Stimulation Reduces Amyloid-beta Peptide Accumulation and Cytotoxicity in Cellular and Animal Models of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE 3xTg-AD mice; Alzheimer's disease; amyloid-beta peptide; amyloid-beta protein precursor; dementia; diabetes; extendin-4; glucagon-like peptide-1; neuroprotection; streptozocin; tau ID GLUCAGON-LIKE PEPTIDE-1; ANGIOTENSIN-CONVERTING ENZYME; BLOOD-BRAIN-BARRIER; A-BETA; DIABETES-MELLITUS; INSULIN-RESISTANCE; VASCULAR DEMENTIA; OXIDATIVE STRESS; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS AB Type 2 (T2) diabetes mellitus (DM) has been associated with an increased incidence of neurodegenerative disorders, including Alzheimer's disease (AD). Several pathological features are shared between diabetes and AD, including dysfunctional insulin signaling and a dysregulation of glucose metabolism. It has therefore been suggested that not only may the two conditions share specific molecular mechanisms but also that agents with proven efficacy in one may be useful against the other. Hence, the present study characterized the effects of a clinically approved long-acting analogue, exendin-4 (Ex-4), of the endogenous insulin releasing incretin, glucagon-like peptide-1 (GLP-1), on stress-induced toxicity in neuronal cultures and on amyloid-beta protein (A beta) and tau levels in triple transgenic AD (3xTg-AD) mice with and without streptozocin (STZ)-induced diabetes. Ex-4 ameliorated the toxicity of A beta and oxidative challenge in primary neuronal cultures and human SH-SY5Y cells in a concentration-dependent manner. When 11 to 12.5 month old female 3xTg AD mice were challenged with STZ or saline, and thereafter treated with a continuous subcutaneous infusion of Ex-4 or vehicle, Ex-4 ameliorated the diabetic effects of STZ in 3xTg-AD mice, elevating plasma insulin and lowering both plasma glucose and hemoglobin A1c (HbA1c) levels. Furthermore, brain levels of A beta protein precursor and A beta, which were elevated in STZ 3xTg-AD mice, were significantly reduced in Ex-4 treated mice. Brain tau levels were unaffected following STZ challenge, but showed a trend toward elevation that was absent following Ex-4 treatment. Together, these results suggest a potential value of Ex-4 in AD, particularly when associated with T2DM or glucose intolerance. C1 [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Biomed Res Ctr,Intramural Res Program, Baltimore, MD 21224 USA. [Duffy, Kara B.; Ottinger, Mary Ann] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Ray, Balmiki; Bailey, Jason A.; Lahiri, Debomoy K.] Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN USA. [Sambamurti, Kumar] Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Biomed Res Ctr,Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM greign@grc.nia.nih.gov RI Ray, Balmiki/F-5445-2011; Mattson, Mark/F-6038-2012 FU National Institute on Aging, NIH; Medstar Research Institute; NIH [U01-AG21380-03, AG023055, RO1-AG18379, RO1-AG18884, P30-AG10133] FX The authors are grateful to Esther Oh, M. D., Division of Geriatric Medicine & Gerontology, Johns Hopkins University, for significant input. The described research was supported in part by the Intramural Research Program, National Institute on Aging, NIH. DT was supported by the Medstar Research Institute, MAO and KBD were supported in part by NIH grant U01-AG21380-03. KS was supported in part by NIH grant AG023055, and DKL together with RB and JAB were supported by grants from NIH (RO1-AG18379, RO1-AG18884 and P30-AG10133). NR 71 TC 130 Z9 137 U1 5 U2 30 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2010 VL 19 IS 4 BP 1205 EP 1219 DI 10.3233/JAD-2010-1314 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 582SS UT WOS:000276619700011 PM 20308787 ER PT J AU Shakleya, DM Dams, R Choo, RE Jones, H Huestis, MA AF Shakleya, Diaa M. Dams, Riet Choo, Robin E. Jones, Hendree Huestis, Marilyn A. TI Simultaneous Liquid Chromatography-Mass Spectrometry Quantification of Urinary Opiates, Cocaine, and Metabolites in Opiate-Dependent Pregnant Women in Methadone-Maintenance Treatment SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID ANHYDROECGONINE METHYL-ESTER; ABUSE TREATMENT PATIENTS; SOLID-PHASE EXTRACTION; EXCRETION PATTERNS; POSTMORTEM FLUIDS; ILLICIT HEROIN; HUMAN PLASMA; ORAL FLUID; DRUGS; METHYLECGONIDINE C1 [Huestis, Marilyn A.] NIDA, Biomed Res Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Choo, Robin E.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Jones, Hendree] Johns Hopkins Bayview Med Ctr, Ctr Addict & Pregnancy, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Biomed Res Ctr, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 5A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health [R01 DA12403] FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health and National Institute on Drug Abuse grant R01 DA12403 (PI-HE Jones). We thank the patients for their participation and the clinical and research staff of the Center for Addiction and Pregnancy. NR 52 TC 17 Z9 17 U1 1 U2 6 PU PRESTON PUBL INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JAN-FEB PY 2010 VL 34 IS 1 BP 17 EP 25 PG 9 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 546EJ UT WOS:000273792500002 PM 20109298 ER PT J AU McCarrey, JR Eddy, EM AF McCarrey, John R. Eddy, E. Mitchell TI Introductory Overview to the Proceedings of the XXth North American Testis Workshop SO JOURNAL OF ANDROLOGY LA English DT Editorial Material C1 [McCarrey, John R.] Univ Texas San Antonio, San Antonio, TX 78249 USA. [Eddy, E. Mitchell] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. RP McCarrey, JR (reprint author), Univ Texas San Antonio, San Antonio, TX 78249 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JAN-FEB PY 2010 VL 31 IS 1 SI SI BP 1 EP 4 DI 10.2164/jandrol.109.009480 PG 4 WC Andrology SC Endocrinology & Metabolism GA 560XP UT WOS:000274938700001 PM 19875486 ER PT J AU Schlessinger, D Garcia-Ortiz, JE Forabosco, A Uda, M Crisponi, L Pelosi, E AF Schlessinger, David Garcia-Ortiz, Jose-Elias Forabosco, Antonino Uda, Manuela Crisponi, Laura Pelosi, Emanuele TI Determination and Stability of Gonadal Sex SO JOURNAL OF ANDROLOGY LA English DT Article; Proceedings Paper CT 20th North American Testis Workshop on Testicular Function - Levels of Regulation CY APR 01-04, 2009 CL Philadelphia, PA DE Sex determination; ovary; testis; Foxl2; sex reversal; gonadal development ID TRANSCRIPTION FACTOR FOXL2; CELL-DIFFERENTIATION; OVARIAN DEVELOPMENT; INVERSUS SYNDROME; TRANSGENIC MICE; BETA-CATENIN; MOUSE OVARY; GERM-CELLS; FEMALE; GENE AB The discovery that the SRY gene induces male sex in humans and other mammals led to speculation about a possible equivalent for female sex. But females are proving to be more complicated. Several master genes appear to be autonomously involved, and female sex determination seems to remain relatively labile. Partial loss of function of the transcription factor FOXL2 leads to premature ovarian failure in women; and in animal models, Foxl2 is required for folliculogenesis as well as for maintenance, and possibly induction, of female sex determination. In the germ line, oocytes apparently form normally even in the absence of Foxl2, dependent on genes that include female-specific factors such as Fig-alpha, Nobox, etc. In the soma, ablation of Foxl2 or the independently expressed gene Wnt4 (likely downstream of Rspo1) can produce partial testis differentiation in XX mice, and the double knockout results in the formation of tubules and spermatogonia. This indicates that at least 2 autonomous ovarian pathways are required to antagonize testis differentiation in females, a finding that is being increasingly corroborated by studies in goats and nonmammalian vertebrates. In recent expression profiling of mouse ovaries that lack Foxl2 alone or in combination with Wnt4 or Kit/c-Kit, we found that following Foxl2 loss, early testis genes (including the downstream effector of Sry, Sox9) and several novel ovarian genes were consistently dysregulated during embryo-fetal development. The results support the proposal of dose-dependent Foxl2 function and antitestis action. A partial working model for somatic development and sex determination is presented in which Sox9 is a direct antagonist of Foxl2 in the supporting cell lineage. C1 [Schlessinger, David; Pelosi, Emanuele] NIA, Genet Lab, IRP, Baltimore, MD 21224 USA. [Garcia-Ortiz, Jose-Elias] CMNO IMSS, Ctr Invest Biomed Occidente, Div Genet, Guadalajara, Jalisco, Mexico. [Forabosco, Antonino] Univ Modena, Unita Genet Med, I-41100 Modena, Italy. [Uda, Manuela; Crisponi, Laura] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. RP Schlessinger, D (reprint author), NIA, Genet Lab, IRP, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM SchlessingerD@mail.nih.gov OI Pelosi, Emanuele/0000-0003-1890-9821 FU Intramural NIH HHS [Z01 AG000647-11] NR 52 TC 23 Z9 23 U1 1 U2 13 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JAN-FEB PY 2010 VL 31 IS 1 SI SI BP 16 EP 25 DI 10.2164/jandrol.109.008201 PG 10 WC Andrology SC Endocrinology & Metabolism GA 560XP UT WOS:000274938700004 PM 19875493 ER PT J AU Tsai-Morris, CH Sheng, Y Gutti, RK Tang, PZ Dufau, ML AF Tsai-Morris, Chon-Hwa Sheng, Yi Gutti, Ravi K. Tang, Pei-Zhong Dufau, Maria L. TI Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25): A Multifunctional Protein Essential for Spermatogenesis SO JOURNAL OF ANDROLOGY LA English DT Article; Proceedings Paper CT 20th North American Testis Workshop on Testicular Function - Levels of Regulation CY APR 01-04, 2009 CL Philadelphia, PA DE Testis; spermiogenesis; messenger ribonuclear protein particle; shuttling protein; translation; phosphorylation; chromatoid body; apoptosis; infertility; single-nuclectide polymorphism (SNP); missense mutation ID DEAD-BOX PROTEINS; ANDROGEN RECEPTOR; CHROMATOID BODY; HAPLOID SPERMATIDS; DROSOPHILA-VASA; SERTOLI-CELLS; GENE; FAMILY; TRANSLATION; EXPRESSION AB Male germ cell maturation is governed by the expression of specific protein(s) in a precise temporal sequence during development. Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), a member of the Glu-Asp-Ala-Glu (DEAD)-box protein family, is a testis-specific gonaclotropin/androgen-regulated RNA helicase that is present in germ cells (meiotic spermatocytes and round spermatids) and Leydig cells. GRTH is essential for completion of spermatogenesis as a posttranscriptional regulator of relevant genes during germ cell development. Male mice lacking GRTH are sterile with spermatogenic arrest due to failure of round spermatids to elongate, where striking structural changes and reduction in size of chromatoid bodies are observed. GRTH also plays a central role in preventing germ cell apoptosis. In addition to its inherent helicase unwinding/adenosine triphosphatase activities, GRTH binds to specific mRNAs as an integral component of ribonuclear protein particles. As a shuttle protein, GRTH transports target mRNAs from nucleus to the cytoplasm for storage in chromatoid bodies of spermatids, where they await translation during spermatogenesis. GRTH is also associated with polyribosomes to regulate target gene translation. The finding of a missense mutation associated with male infertility, where its expression associates with loss of GRTH phosphorylation, supports the relevance of GRTH to human germ cell development. We conclude that the mammalian GRTH/DDX25 is a multifunctional RNA helicase that is an essential regulator of spermatogenesis and is highly relevant for studies of male infertility and contraception. C1 [Tsai-Morris, Chon-Hwa; Sheng, Yi; Gutti, Ravi K.; Tang, Pei-Zhong; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Tsai-Morris, CH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bldg 49,Rm 6B-03,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM morrisch@mail.nih.gov OI Gutti, Ravi/0000-0002-0912-5796 FU Intramural NIH HHS [ZIA HD000150-36] NR 35 TC 19 Z9 23 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JAN-FEB PY 2010 VL 31 IS 1 SI SI BP 45 EP 52 DI 10.2164/jandrol.109.008219 PG 8 WC Andrology SC Endocrinology & Metabolism GA 560XP UT WOS:000274938700007 PM 19875492 ER PT J AU Goldberg, E Eddy, EM Duan, CW Odet, F AF Goldberg, Erwin Eddy, Edward M. Duan, Chongwen Odet, Fanny TI LDHC: The Ultimate Testis-Specific Gene SO JOURNAL OF ANDROLOGY LA English DT Article; Proceedings Paper CT 20th North American Testis Workshop on Testicular Function - Levels of Regulation CY APR 01-04, 2009 CL Philadelphia, PA DE Lactate dehydrogenase C; glycolysis; male fertility; sperm ID LACTATE-DEHYDROGENASE-C; MOUSE SPERMATOGENIC CELLS; MALE GERM-CELLS; IN-VITRO; LACTIC DEHYDROGENASE; GEL ELECTROPHORESIS; PROMOTER ACTIVITY; DNA METHYLATION; TRANSGENIC MICE; MALE-FERTILITY AB Lactate dehydrogenase C (LDHC) was, to the best of our knowledge, the first testis-specific isozyme discovered in male germ cells. In fact, this was accomplished shortly before "isozymes or isoenzymes" became a field of study. LDHC was detected initially in human spermatozoa and spermatogenic cells of the testes by gel electrophoresis. Immunohistochemistry was used to localize LDHC first in early-pachytene primary spermatocytes, with an apparent increase in quantity after meiosis, to its final localization in and on the principal piece of the sperm tail. After several decades of biologic, biochemical, and genetic investigations, we now know that the lactate dehydrogenase isozymes are ubiquitous in vertebrates, developmentally regulated, tissue and cell specific, and multifunctional. Here, we will review the history of LDHC and the work that demonstrates clearly that it is required for sperm to accomplish their ultimate goal, fertilization. C1 [Goldberg, Erwin; Duan, Chongwen] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. [Eddy, Edward M.; Odet, Fanny] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. RP Goldberg, E (reprint author), Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. EM erv@northwestern.edu FU Intramural NIH HHS [Z01 ES070076-22]; NICHD NIH HHS [HD05863, R01 HD005863] NR 83 TC 38 Z9 42 U1 1 U2 4 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JAN-FEB PY 2010 VL 31 IS 1 SI SI BP 86 EP 94 DI 10.2164/jandrol.109.008367 PG 9 WC Andrology SC Endocrinology & Metabolism GA 560XP UT WOS:000274938700013 PM 19875487 ER PT J AU Riskind, JH Black, D Shahar, G AF Riskind, John H. Black, David Shahar, Golan TI Cognitive vulnerability to anxiety in the stress generation process: Interaction between the Looming Cognitive Style and Anxiety Sensitivity SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Cognitive vulnerability to anxiety and stress generation; Predicting stress generation; Looming Cognitive Style; Anxiety Sensitivity ID DEPRESSIVE SYMPTOMS; DISORDER SYMPTOMS; MALADAPTIVE STYLE; SPECIFICITY; PERSONALITY; DIMENSIONS; PREDICTION; INVENTORY; RESOURCE; DANGER AB This study sought to extend the investigation of cognitive-personality vulnerability in the stress generation process to the field of anxiety. We examined two well documented cognitive vulnerabilities to anxiety: the Looming Cognitive Style (LCS) and Anxiety Sensitivity (ASI). Investigating 72 undergraduates who were assessed twice over a 4-month interval, we found support for the hypothesis that the two cognitive vulnerabilities to anxiety augment each other's stress generating effect. Results indicated that combination of LCS and ASI together had a far stronger stress generation effect that would just one factor alone. Each factor was positively associated with Time 2 stressful events under high levels of the other, but not under low levels. Thus findings revealed that the joint combination of the two cognitive vulnerabilities seemed to play a particularly marked role over a 4-month time interval. These findings are important because they are among the first to show stress generation effects for anxiety-related cognitive styles. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Riskind, John H.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Shahar, Golan] Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. [Black, David] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. RP Riskind, JH (reprint author), George Mason Univ, Dept Psychol, 440 Univ Dr, Fairfax, VA 22030 USA. EM jriskind@gmu.edu RI Shahar, Golan/F-1502-2012 NR 40 TC 27 Z9 28 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN PY 2010 VL 24 IS 1 BP 124 EP 128 DI 10.1016/j.janxdis.2009.09.007 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 542PI UT WOS:000273506500017 PM 19854612 ER PT J AU Shear, WA Snyder, AJ Jones, TH Garraffo, HM Andriamaharavo, NR AF Shear, William A. Snyder, Alexander J. Jones, Tappey H. Garraffo, H. Martin Andriamaharavo, N. Rabe TI The chemical defense of the Texas cave harvestman Chinquipellobunus madlae: first report on the family Stygnopsidae and on a North American troglobiont harvestman (Opilones: Gonyleptoidea) SO JOURNAL OF ARACHNOLOGY LA English DT Article DE Secretion; 2-methyl-5-ethylphenol; 2,5-dimethylphenol ID BEHAVIORAL DEFENSES; OPILIONES; ARACHNIDA; GONYLEPTIDAE; SECRETIONS; LANIATORES AB The stygnopsid harvestman Chinquipellobunus madlae (Goodnight and Goodnight 1967) is known from numerous caves in eleven counties in Texas and is a highly adapted troglobiont (Cokendolpher 2004). Adult and juvenile specimens were extracted in methanol, and the major volatile component of their chemical defense secretion was identified as 2-methyl-5-ethylphenol; a minor component was 2, 5-dimethylphenol. Methylethyl phenols and dimethyl phenols have also been identified in other grassatorid Opiliones, but this is the first report of defensive chemistry from a member of the family Stygnopsidae and from a North American troglobiont harvestman. C1 [Shear, William A.] Hampden Sydney Coll, Dept Biol, Hampden Sydney, VA 23943 USA. [Snyder, Alexander J.; Jones, Tappey H.] Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. [Garraffo, H. Martin; Andriamaharavo, N. Rabe] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shear, WA (reprint author), Hampden Sydney Coll, Dept Biol, Hampden Sydney, VA 23943 USA. EM wshear@hsc.edu NR 17 TC 6 Z9 7 U1 1 U2 2 PU AMER ARACHNOLOGICAL SOC PI COLLEGE PARK PA UNIV MARYLAND, DEPT ENTOMOLOGY, 4112 PLANT SCIENCES BLDG, COLLEGE PARK, MD 20742-4454 USA SN 0161-8202 J9 J ARACHNOL JI J. Arachnol. PY 2010 VL 38 IS 1 BP 126 EP 127 PG 2 WC Entomology SC Entomology GA 573NU UT WOS:000275921400016 ER PT J AU Akita, N Tsujita, M Yokota, T Gonzalez, FJ Ohte, N Kimura, G Yokoyama, S AF Akita, Nobukatsu Tsujita, Maki Yokota, Tomo Gonzalez, Frank J. Ohte, Nobuyuki Kimura, Genjiro Yokoyama, Shinji TI High Density Lipoprotein Turnover is Dependent on Peroxisome Proliferator-Activated Receptor alpha in Mice SO JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS LA English DT Article DE PPAR alpha; HDL; Cholesterol; ABCA1; SRB1; Steroidogenic ID PPAR-ALPHA; GENE-EXPRESSION; INSULIN-RESISTANCE; DIABETES-MELLITUS; DEFICIENT MICE; NULL MICE; I GENE; CHOLESTEROL; METABOLISM; MOUSE AB Aim: Peroxisome proliferator-activated receptor (PPAR) alpha is a nuclear receptor that through sensing fatty acid metabolites as ligands regulates genes involved in lipid transport and metabolism (Atherosclerosis 205: 413, 2009). Disruption of the PPAR alpha gene, however, may not lead to apparent changes in phenotypes, perhaps due to compensation by other members of the nuclear receptor superfamily. We characterized cholesterol homeostasis in PPAR alpha-null mice on a C57BL/6 background with a focus on HDL metabolism. Methods and Results: PPAR alpha-null mice gained weight significantly more than wild-type mice, with more prominence in females, without changing the HDL-apoprotein clearance rate. Clearance of plasma HDL-cholesteryl ester was retarded, more prominently in females. Uptake of HDL-cholesteryl ester by the adrenal glands and ovaries was found to be decreased in female mutant mice. The ATP binding cassette transporter A1 (ABCA1), liver X receptor alpha and PPAR delta mRNAs were decreased in the liver, and that encoding scavenger receptor B1 (SR-B1) decreased in the adrenal glands of these mice. Although the plasma lipoprotein profile did not show major differences, some subtle changes were found in the mutants, including HDL properties being consistent with its slow turnover. Cholesterol content in the organs was not significantly influenced except for a paradoxical increase in gonad glands. Conclusions: We conclude that the plasma HDL turnover rate is retarded in PPARa-null mice, perhaps more prominently in females. C1 [Akita, Nobukatsu; Tsujita, Maki; Yokota, Tomo; Ohte, Nobuyuki; Kimura, Genjiro; Yokoyama, Shinji] Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi 4678601, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Yokoyama, S (reprint author), Nagoya City Univ, Grad Sch Med Scices, Mizuho Ku, Kawasumi 1,Mizuho Cho, Nagoya, Aichi 4678601, Japan. EM syokoyam@med.nagoya-cu.ac.jp FU Ministry of Education, Culture Science, Sports and Technology, and of Health, Welfare and Labor of Japan; National Institute of Biomedical Innovation FX This study was supported by grants-in-aids from the Ministry of Education, Culture Science, Sports and Technology, and of Health, Welfare and Labor of Japan, and by the Program for Promotion of Fundamental Studies in Health Sciences of National Institute of Biomedical Innovation. NR 36 TC 3 Z9 5 U1 0 U2 1 PU JAPAN ATHEROSCLEROSIS SOC PI TOKYO PA NICHINAI-KAIKAN B1, 3-28-8 HONGO BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1340-3478 EI 1880-3873 J9 J ATHEROSCLER THROMB JI J. Atheroscler. Thromb. PY 2010 VL 17 IS 11 BP 1149 EP 1159 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 690OS UT WOS:000285014700005 PM 20668363 ER PT J AU Casanova, MF El-Baz, AS Giedd, J Rumsey, JM Switala, AE AF Casanova, Manuel F. El-Baz, Ayman S. Giedd, Jay Rumsey, Judith M. Switala, Andrew E. TI Increased White Matter Gyral Depth in Dyslexia: Implications for Corticocortical Connectivity SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autistic disorder; Cerebrum; Corpus callosum; Dyslexia; Gyral window ID DEVELOPMENTAL DYSLEXIA; CORPUS-CALLOSUM; MINICOLUMNAR PATHOLOGY; READING-DISABILITY; GRAY-MATTER; PLANUM TEMPORALE; WORD RECOGNITION; CEREBRAL-CORTEX; AUTISM; CHILDREN AB Recent studies provide credence to the minicolumnar origin of several developmental conditions, including dyslexia. Characteristics of minicolumnopathies include abnormalities in how the cortex expands and folds. This study examines the depth of the gyral white matter measured in an MRI series of 15 dyslexic adult men and eleven age-matched comparison subjects. Measurements were based upon the 3D Euclidean distance map inside the segmented cerebral white matter surface. Mean gyral white matter depth was 3.05 mm (SD +/- 0.30 mm) in dyslexic subjects and 1.63 mm (SD +/- 0.15 mm) in the controls. The results add credence to the growing literature suggesting that the attained reading circuit in dyslexia is abnormal because it is inefficient. Otherwise the anatomical substratum (i.e., corticocortical connectivity) underlying this inefficient circuit is normal. A deficit in very short-range connectivity (e.g., angular gyrus, striate cortex), consistent with results of a larger gyral window, could help explain reading difficulties in patients with dyslexia. The structural findings hereby reported are diametrically opposed to those reported for autism. C1 [Casanova, Manuel F.; Switala, Andrew E.] Univ Louisville, Dept Psychiat & Behav Sci, Louisville, KY 40292 USA. [El-Baz, Ayman S.] Univ Louisville, Dept Biomed Engn, Louisville, KY 40292 USA. [Giedd, Jay] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Rumsey, Judith M.] NIMH, Neurodev Disorders Res Branch, Bethesda, MD 20892 USA. RP Casanova, MF (reprint author), 500 S Preston St,Bldg 55A Rm 217, Louisville, KY 40292 USA. EM manuel.casanova@louisville.edu 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; El-Baz, Ayman/0000-0001-7264-1323 FU Intramural NIH HHS [ZIA MH002794-08]; NIMH NIH HHS [MH62654, MH69991, R01 MH062654, R01 MH069991] NR 75 TC 12 Z9 12 U1 4 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JAN PY 2010 VL 40 IS 1 BP 21 EP 29 DI 10.1007/s10803-009-0817-1 PG 9 WC Psychology, Developmental SC Psychology GA 545HB UT WOS:000273722000003 PM 19609661 ER PT J AU Hemm, MR Paul, BJ Miranda-Rios, J Zhang, AX Soltanzad, N Storz, G AF Hemm, Matthew R. Paul, Brian J. Miranda-Rios, Juan Zhang, Aixia Soltanzad, Nima Storz, Gisela TI Small Stress Response Proteins in Escherichia coli: Proteins Missed by Classical Proteomic Studies SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CAMP-RECEPTOR PROTEIN; HEAT-SHOCK; COMPARATIVE GENOMICS; BACILLUS-SUBTILIS; GROWTH-CONDITIONS; STATIONARY-PHASE; RNA THERMOMETERS; ACID RESISTANCE; GENE-EXPRESSION; WEB SERVER AB Proteins of 50 or fewer amino acids are poorly characterized in all organisms. The corresponding genes are challenging to reliably annotate, and it is difficult to purify and characterize the small protein products. Due to these technical limitations, little is known about the abundance of small proteins, not to mention their biological functions. To begin to characterize these small proteins in Escherichia coli, we assayed their accumulation under a variety of growth conditions and after exposure to stress. We found that many small proteins accumulate under specific growth conditions or are stress induced. For some genes, the observed changes in protein levels were consistent with known transcriptional regulation, such as ArcA activation of the operons encoding yccB and ybgT. However, we also identified novel regulation, such as Zur repression of ykgMO, cyclic AMP response protein (CRP) repression of azuC, and CRP activation of ykgR. The levels of 11 small proteins increase after heat shock, and induction of at least 1 of these, YobF, occurs at a posttranscriptional level. These results show that small proteins are an overlooked subset of stress response proteins in E. coli and provide information that will be valuable for determining the functions of these proteins. C1 [Hemm, Matthew R.; Paul, Brian J.; Miranda-Rios, Juan; Zhang, Aixia; Soltanzad, Nima; Storz, Gisela] Eunice Kennedy Shriver NICHHD, Cell Biol & Metab Program, Bethesda, MD 20892 USA. RP Storz, G (reprint author), NIH, Bldg 18T,Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. EM storz@helix.nih.gov OI Storz, Gisela/0000-0001-6698-1241 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Life Sciences Foundation; National Research Council FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by postdoctoral fellowships from the Life Sciences Foundation (M. R. H.) and the National Research Council (B. J. P.). NR 53 TC 51 Z9 76 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2010 VL 192 IS 1 BP 46 EP 58 DI 10.1128/JB.00872-09 PG 13 WC Microbiology SC Microbiology GA 531BB UT WOS:000272636600006 PM 19734316 ER PT J AU Hobbs, EC Astarita, JL Storz, G AF Hobbs, Errett C. Astarita, Jillian L. Storz, Gisela TI Small RNAs and Small Proteins Involved in Resistance to Cell Envelope Stress and Acid Shock in Escherichia coli: Analysis of a Bar-Coded Mutant Collection SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE GENOME; BACTERIAL OUTER-MEMBRANE; SMALL NONCODING RNAS; MESSENGER-RNA; E. COLI; TRANS-TRANSLATION; REGULATORY RNAS; GENE-DELETION; SYSTEM; K-12 AB More than 80 small regulatory RNAs (sRNAs) and 60 proteins of 16 to 50 amino acids (small proteins) are encoded in the Escherichia coli genome. The vast majority of the corresponding genes have no known function. We screened 125 DNA bar-coded mutants to identify novel cell envelope stress and acute acid shock phenotypes associated with deletions of genes coding for sRNAs and small proteins. Nine deletion mutants (ssrA, micA, ybaM, ryeF, yqcG, sroH, ybhT, yobF, and glmY) were sensitive to cell envelope stress and two were resistant (rybB and blr). Deletion mutants of genes coding for four small proteins (yqgB, mgrB, yobF, and yceO) were sensitive to acute acid stress. We confirmed each of these phenotypes in one-on-one competition assays against otherwise-wild-type lacZ mutant cells. A more detailed investigation of the SsrA phenotype suggests that ribosome release is critical for resistance to cell envelope stress. The bar-coded deletion collection we generated can be screened for sensitivity or resistance to virtually any stress condition. C1 [Hobbs, Errett C.; Astarita, Jillian L.; Storz, Gisela] Eunice Kennedy Shriver NICHHD, Cell Biol & Metab Program, Bethesda, MD 20892 USA. RP Storz, G (reprint author), NIH, Bldg 18T,Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. EM storz@helix.nih.gov OI Storz, Gisela/0000-0001-6698-1241 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Pharmacology Research Associate Program at the National Institute of General Medical Sciences FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (E. C. H., J. L. A., and G. S.) and by the Pharmacology Research Associate Program at the National Institute of General Medical Sciences (E. C. H.). NR 55 TC 40 Z9 42 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2010 VL 192 IS 1 BP 59 EP 67 DI 10.1128/JB.00873-09 PG 9 WC Microbiology SC Microbiology GA 531BB UT WOS:000272636600007 PM 19734312 ER PT J AU Braithwaite, EK Mattie, MD Freedman, JH AF Braithwaite, Elena K. Mattie, Michael D. Freedman, Jonathan H. TI Activation of Metallothionein Transcription by 4-Hydroxynonenal SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE 4-Hydroxynonenal; Metallothionein; Transcription; Oxidative Stress; Reactive Oxygen Species ID METAL-RESPONSIVE TRANSCRIPTION; NF-KAPPA-B; LIPID-PEROXIDATION; OXIDATIVE STRESS; GENE-EXPRESSION; I GENE; INDUCIBLE TRANSCRIPTION; SUBUNIT TRANSCRIPTION; FACTOR MTF-1; END-PRODUCT AB Metallothioneins (MTs) protect cells from oxidative damage by scavenging reactive oxygen species (ROS). Concurrent with protecting cells from ROS-mediated damage, MT transcription is induced by ROS. ROS activate transcription by affecting several signal transduction pathways, many of which have been implicated in regulating MT transcription. ROS-activated intracellular signaling is mediated by the stable lipid peroxide 4-hydroxynonenal (HNE). After determining the level of sensitivity of Hepa 1-6 cells to HNE, MT-1 mRNA expression was shown to be induced in a concentration and time-dependent manner after HNE exposure. Finally, using MT-based reporters, HNE was found to induce MT transcription via both antioxidant response and metal response elements. Thus, ROS may activate MT transcription by generating HNE that in turn affects signaling pathways that regulate MT transcription via the transcription factors AP-1 and MTF-1. (C) 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:330-334, 2010; View this article online at wileyonlinelibrary.com. DOI 10:1002/jbt.20342 C1 [Braithwaite, Elena K.; Freedman, Jonathan H.] NIEHS, NIH, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Mattie, Michael D.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. RP Freedman, JH (reprint author), NIEHS, NIH, Mol Toxicol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM freedma1@nichs.nih.gov FU NIH [Z01ES102045] FX Contract Grant Sponsor: Intramural Research Program of the NIH.; Contract Grant Number: Z01ES102045. NR 31 TC 8 Z9 8 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2010 VL 24 IS 5 BP 330 EP 334 DI 10.1002/jbt.20342 PG 5 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 676ZQ UT WOS:000283959100007 PM 20979157 ER PT J AU Qualley, DF Stewart-Maynard, KM Wang, F Mitra, M Gorelick, RJ Rouzina, I Williams, MC Musier-Forsyth, K AF Qualley, Dominic F. Stewart-Maynard, Kristen M. Wang, Fei Mitra, Mithun Gorelick, Robert J. Rouzina, Ioulia Williams, Mark C. Musier-Forsyth, Karin TI C-terminal Domain Modulates the Nucleic Acid Chaperone Activity of Human T-cell Leukemia Virus Type 1 Nucleocapsid Protein via an Electrostatic Mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRANDED DNA; GENOMIC RNA DIMERIZATION; ZINC-FINGER STRUCTURES; INTEGRATION IN-VITRO; PRIMER BINDING-SITE; REVERSE TRANSCRIPTION; GENE-32 PROTEIN; VIRAL-RNA; STRUCTURAL DETERMINANTS; THERMODYNAMIC ANALYSIS AB Retroviral nucleocapsid (NC) proteins are molecular chaperones that facilitate nucleic acid (NA) remodeling events critical in viral replication processes such as reverse transcription. Surprisingly, theNCprotein from human T-cell leukemia virus type 1 (HTLV-1) is an extremely poor NA chaperone. Using bulk and single molecule methods, we find that removal of the anionic C-terminal domain (CTD) of HTLV-1 NC results in a protein with chaperone properties comparable with that of other retroviral NCs. Increasing the ionic strength of the solution also improves the chaperone activity of full-length HTLV-1 NC. To determine how the CTD negatively modulates the chaperone activity of HTLV-1 NC, we quantified the thermodynamics and kinetics of wild-type and mutant HTLV-1 NC/NA interactions. The wild-type protein exhibits very slow dissociation kinetics, and removal of the CTD or mutations that eliminate acidic residues dramatically increase the protein/DNA interaction kinetics. Taken together, these results suggest that the anionic CTD interacts with the cationic N-terminal domain intramolecularly when HTLV-1 NC is not bound to nucleic acids, and similar interactions occur between neighboring molecules when NC is NA-bound. The intramolecular N-terminal domain-CTD attraction slows down the association of the HTLV-1 NC with NA, whereas the intermolecular interaction leads to multimerization of HTLV-1 NC on the NA. The latter inhibits both NA/NC aggregation and rapid protein dissociation from single-stranded DNA. These features make HTLV-1 NC a poor NA chaperone, despite its robust duplex destabilizing capability. C1 [Qualley, Dominic F.; Mitra, Mithun; Musier-Forsyth, Karin] Ohio State Univ, Ctr Retrovirus Res, Dept Chem, Columbus, OH 43210 USA. [Qualley, Dominic F.; Mitra, Mithun; Musier-Forsyth, Karin] Ohio State Univ, Ctr Retrovirus Res, Dept Biochem, Columbus, OH 43210 USA. [Qualley, Dominic F.; Mitra, Mithun; Musier-Forsyth, Karin] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA. [Stewart-Maynard, Kristen M.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Stewart-Maynard, Kristen M.] Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA. [Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. [Wang, Fei; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Gorelick, Robert J.] NCI, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick Inc, NIH, Ft Detrick, MD 21702 USA. RP Rouzina, I (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, 321 Church St SE, Minneapolis, MN 55455 USA. EM rouzi002@umn.edu; ma.williams@neu.edu; musier@chemistry.ohio-state.edu RI Mitra, Mithun/A-2133-2015; OI Williams, Mark C./0000-0003-3219-376X FU National Institutes of Health [GM065056, GM072462]; Ruth L. Kirschstein National Service Award [GM072396]; NCI [N01-CO-12400, HHSN261200800001E]; National Science Foundation [MCB-0744456] FX This work was supported, in whole or in part, by National Institutes of Health Grants GM065056 (to K. M. -F.) and GM072462 (to M. C. W.), Ruth L. Kirschstein National Service Award GM072396 (to K. M. S.- M.), and Contracts N01-CO-12400 and HHSN261200800001E from the NCI. This work was also supported by National Science Foundation Grant MCB-0744456 (to M. C. W.). NR 85 TC 26 Z9 26 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 1 PY 2010 VL 285 IS 1 BP 295 EP 307 DI 10.1074/jbc.M109.051334 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 536UT UT WOS:000273070100031 PM 19887455 ER PT J AU Chawla, B Jhingran, A Singh, S Tyagi, N Park, MH Srinivasan, N Roberts, SC Madhubala, R AF Chawla, Bhavna Jhingran, Anupam Singh, Sushma Tyagi, Nidhi Park, Myung Hee Srinivasan, N. Roberts, Sigrid C. Madhubala, Rentala TI Identification and Characterization of a Novel Deoxyhypusine Synthase in Leishmania donovani SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; ENZYME-SUBSTRATE INTERMEDIATE; VISCERAL LEISHMANIASIS; CELL VIABILITY; AMINO-ACID; 3-DIMENSIONAL STRUCTURES; HYPUSINE FORMATION; CRYSTAL-STRUCTURE; PROTEIN; SPERMIDINE AB Deoxyhypusine synthase, an NAD(+)-dependent enzyme, catalyzes the first step in the post-translational synthesis of an unusual amino acid, hypusine (N(epsilon)-(4-amino-2-hydroxybutyl)lysine), in the eukaryotic initiation factor 5A precursor protein. Two putative deoxyhypusine synthase (DHS) sequences have been identified in the Leishmania donovani genome, which are present on chromosomes 20: DHSL20 (DHS-like gene from chromosome 20) and DHS34 (DHS from chromosome 34). Although both sequences exhibit an overall conservation of key residues, DHSL20 protein lacks a critical lysine residue, and the recombinant protein showed no DHS activity in vitro. However, DHS34 contains the critical lysine residue, and the recombinant DHS34 effectively catalyzed deoxyhypusine synthesis. Furthermore, in vivo labeling confirmed that hypusination of eukaryotic initiation factor 5A occurs in intact Leishmania parasites. Interestingly, the DHS34 is much longer, with 601 amino acids, compared with the human DHS enzyme (369 amino acids) and contains several unique insertions. To study the physiological role of DHS34 in Leishmania, gene deletion mutations were attempted via targeted gene replacement. However, chromosomal null mutants of DHS34 could only be obtained in the presence of a DHS34-containing episome. The present data provide evidence that DHS34 is essential for L. donovani and that structural differences in the human and leishmanial DHS enzyme may be exploited for designing selective inhibitors against the parasite. C1 [Chawla, Bhavna; Jhingran, Anupam; Singh, Sushma; Madhubala, Rentala] Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India. [Tyagi, Nidhi; Srinivasan, N.] Indian Inst Sci, Mol Biophys Unit, Bangalore 560012, Karnataka, India. [Park, Myung Hee] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Roberts, Sigrid C.] Pacific Univ, Sch Pharm, Portland, OR 97123 USA. RP Madhubala, R (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India. EM madhubala@mail.jnu.ac.in RI madhubala, Rentala/C-3445-2015; OI Tyagi, Nidhi/0000-0002-2065-9051; madhubala, rentala/0000-0002-0034-399X FU National Institutes of Health; Council of Scientific and Industrial Research, India FX This work was authored, in whole or in part, by National Institutes of Health staff. This work is supported by a grant from the Council of Scientific and Industrial Research, India ( to R. M.). NR 51 TC 18 Z9 21 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 1 PY 2010 VL 285 IS 1 BP 453 EP 463 DI 10.1074/jbc.M109.048850 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 536UT UT WOS:000273070100047 PM 19880510 ER PT J AU Marotta, F Harada, M Dallah, ED Yadav, H Solimene, U Di Lembo, S Minelli, E Jain, S Chui, DH AF Marotta, F. Harada, M. Dallah, E. D. Yadav, H. Solimene, U. Di Lembo, S. Minelli, E. Jain, S. Chui, D. H. TI PROTECTIVE EFFECT OF A POLY-PHYTOCOMPOUND ON EARLY STAGE NEPHROPATHY SECONDARY TO EXPERIMENTALLY-INDUCED DIABETES SO JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS LA English DT Article DE diabetic nephropathy; oxidative stress; DTS ID NEPHRIN MESSENGER-RNA; OXIDATIVE STRESS; PROGRESSION; EXPRESSION; MELLITUS; KIDNEY; ASSAY; MODULATION; GLUCOSE; INJURY AB Diabetic nephropathy (DN) is a severe and life-threatening complication of long-standing diabetes. As one of the main causes of end-stage renal disease, the prevention and treatment of DN in early stage, and the slowing down of DN progression are of utmost importance and are topics of several ongoing research studies. Nutraceuticals endowed with antioxidant-anti-inflammatory properties may offer an opportunity of integrative treatment for this condition. Male Wistar rats were randomly assigned to two groups. One group of rats (diabetic group) received a single tail-vein injection of STZ compound (50 mg/kg) under light anaesthesia. A protective dose of 0.5 ml of 5% dextrose was given intraperitoneally 30 min before the administration of STZ. One diabetic group was fed a normal pellet diet (group A) while group B was fed the diet added with DTS (panax pseudoginseng, eucommia ulmoides), (Kyotsu Jigyo, Tokyo, Japan) in the proportion of 50/25 (% weight/weight), at the dose of 50 mg/kg/day throughout the experimental period. At the end of 8 weeks, 24-hour urine was collected for the measurement of the albumin concentration: blood samples were collected for serum biochemistry and the rats were sacrificed for kidney measurement of oxidative stress- and histo-morphological features. Nephrin and Macrophage Chemoattractant Protein-1 (MCP-1) gene expression were also assessed by fluorescence real-time quantitative PCR after RNA extraction and cDNA synthesis. STZ-treated animals showed significantly increased in lipid peroxidation in the kidney and in proteinuria. DTS supplementation did not affect plasma glucose but significantly decreased malonyldialdehyde (MDA) plasma level and the overall redox parameters together with a partial mitigation of proteinuria. Histological analysis showed also that DTS significantly reduced the glomerular volume together with glomerulosclerosis and interstitial fibrosis score (p<0.05), the latter two being correlated to proteinuria (p<0.05). DTS supplementation also enabled a reduction of diabetes-induced decrease of nephrin mRNA expression and a 67% reduction of MCP-1 mRNA up-regulation (p<0.01). Taken altogether, these data show that, besides the mandatory control of glycemia, intervention with a nutraceutical with antioxidant and anti-inflammatory properties may have beneficial effects when integrated in the mainstream of the therapeutic regimen. C1 [Marotta, F.; Solimene, U.; Minelli, E.] Univ Milan, WHO Ctr Biotech & Tradit Med, I-20122 Milan, Italy. [Harada, M.; Dallah, E. D.] MHC Hosp, Tokyo, Japan. [Yadav, H.] NIDDK, NIH, Bethesda, MD USA. [Jain, S.] Univ Illinois, Dept Food Sci & Human Nutr, Chicago, IL 60680 USA. [Chui, D. H.] Peking Univ, Neurosci Res Inst, Beijing, Peoples R China. [Marotta, F.; Di Lembo, S.] S Giuseppe Hosp, Endocrinol Unit, I-20122 Milan, Italy. RP Marotta, F (reprint author), S Giuseppe Hosp, Endocrinol Unit, Via S Vittore 12, I-20122 Milan, Italy. EM fmarchimede@libero.it NR 34 TC 14 Z9 15 U1 1 U2 2 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0393-974X EI 1724-6083 J9 J BIOL REG HOMEOS AG JI J. Biol. Regul. Homeost. Agents PD JAN-MAR PY 2010 VL 24 IS 1 BP 41 EP 49 PG 9 WC Endocrinology & Metabolism; Immunology; Medicine, Research & Experimental; Physiology SC Endocrinology & Metabolism; Immunology; Research & Experimental Medicine; Physiology GA 593CK UT WOS:000277429300005 PM 20385070 ER PT J AU Khormaee, S Chen, RJ Park, JK Slater, NKH AF Khormaee, Sariah Chen, Rongjun Park, John K. Slater, Nigel K. H. TI The Influence of Aromatic Side-Chains on the Aqueous Properties of pH-Sensitive Poly(L-lysine iso-phthalamide) Derivatives SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article DE pH-responsive polymers; membrane disruption; endosome; drug delivery ID RESPONSIVE PSEUDO-PEPTIDES; MEMBRANE-DISRUPTIVE ACTIVITY; CYTOPLASMIC DELIVERY; SOLUTION BEHAVIOR; POLYMERS; MODULATION; LIPOSOMES; VECTORS; SYSTEMS; DYE AB The endosomal membrane has proven to be a challenging barrier for the delivery of therapeutic biomacromolecules, including DNA, siRNA and proteins, which are taken up by endosomes but cannot freely diffuse across lipid bilayers. Anionic polymers that undergo conformational changes and become membrane disruptive in low-pH environments have the potential to assist in the delivery of these biomacromolecules across the endosomal membrane to the cytosol. Such endosomolytic polymers have been synthesized through the grafting of hydrophobic side-chains to a poly(L-lysine iso-phthalamide) backbone. The phenylalanine grafted form of poly(L-lysine iso-phthalamide) has a pH-sensitive membrane disruptive profile corresponding to the pH range of maturing endosomes and, thus, has a favourable endosomolytic profile. In order to understand the influence of hydrophobicity versus p-p interactions mediated by aromatic rings, a tyrosine grafted form of poly(L-lysine iso-phthalamide) was synthesized and its aqueous pH-sensitive properties, cytotoxicity and endosomal disruptive capacity were compared to phenylalanine-grafted poly(L-lysine iso-phthalamide). The similarity between these two polymers' properties, despite the large difference in hydrophobicity between their side-chains, supports the conclusion that the aromatic character of side-chains in poly(L-lysine iso-phthalamide) is an important property, as opposed to hydrophobicity alone, in determining the effectiveness of acidic pH triggered endosomolysis. (C) Koninklijke Brill NV, Leiden, 2010 C1 [Khormaee, Sariah; Chen, Rongjun; Slater, Nigel K. H.] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB2 3RA, England. [Khormaee, Sariah; Park, John K.] NINDS, Surg & Mol Neurooncol Unit, NIH, Bethesda, MD 20892 USA. RP Slater, NKH (reprint author), Univ Cambridge, Dept Chem Engn & Biotechnol, Pembroke St, Cambridge CB2 3RA, England. EM nkhs2@cam.ac.uk OI Chen, Rongjun/0000-0002-8133-5472 FU National Institute of Neurological Disorders and Stroke; National Institues of Health; Marshall Aid Commemoration Commission; Gates Cambridge Trust; Universities UK organization FX S. K. is grateful for the financial support of the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institues of Health and the Marshall Aid Commemoration Commission. R. C. wishes to thank the Gates Cambridge Trust and the Universities UK organization for their financial support. NR 29 TC 5 Z9 5 U1 1 U2 8 PU VSP BV PI LEIDEN PA BRILL ACADEMIC PUBLISHERS, PO BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0920-5063 J9 J BIOMAT SCI-POLYM E JI J. Biomater. Sci.-Polym. Ed. PY 2010 VL 21 IS 12 BP 1573 EP 1588 DI 10.1163/092050609X12519805626194 PG 16 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 657EU UT WOS:000282396800003 PM 20537242 ER PT J AU Yin, JC Yang, HC Li, X Zhang, J Zhou, QF Hu, CH Shung, KK Chen, ZP AF Yin, Jiechen Yang, Hao-Chung Li, Xiang Zhang, Jun Zhou, Qifa Hu, Changhong Shung, K. Kirk Chen, Zhongping TI Integrated intravascular optical coherence tomography ultrasound imaging system SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical coherence tomography; intravascular ultrasound; intravascular imaging; dual-modality imaging system ID THIN-CAP FIBROATHEROMA; VULNERABLE PLAQUE; PATHOLOGY AB We report on a dual-modality optical coherence tomography (OCT) ultrasound (US) system for intravascular imaging. To the best of our knowledge, we have developed the first integrated OCT-US probe that combines OCT optical components with an US transducer. The OCT optical components mainly consist of a single-mode fiber, a gradient index lens for light-beam focusing, and a right-angled prism for reflecting light into biological tissue. A 40-MHz piezoelectric transducer (PZT-5H) side-viewing US transducer was fabricated to obtain the US image. These components were integrated into a single probe, enabling both OCT and US imaging at the same time. In vitro OCT and ultrasound images of a rabbit aorta were obtained using this dual-modality imaging system. This study demonstrates the feasibility of an OCT-US system for intravascular imaging, which is expected to have a prominent impact on early detection and characterization of atherosclerosis. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3308642] C1 [Yin, Jiechen; Chen, Zhongping] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA. [Yang, Hao-Chung; Li, Xiang; Zhou, Qifa; Hu, Changhong; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Yang, Hao-Chung; Li, Xiang; Zhou, Qifa; Hu, Changhong; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Zhang, Jun; Chen, Zhongping] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA 92612 USA. RP Chen, ZP (reprint author), Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA. EM z2chen@uci.edu RI Zhang, Jun/A-1801-2014 FU NIH [CA-91717, EB-00293, EB10090, RR-01192]; U.S. Air Force Office of Scientific Research [FA9550-08-1-0384] FX We thank Hongrui Li and Tanya Burney for preparing the tissue and Wei Wei for his assistance during the experiment. This work is based on research supported by the NIH (Grants No. CA-91717, No. EB-00293, No. EB10090, and No. RR-01192) and the U.S. Air Force Office of Scientific Research, Medical Free-Electron Laser Program FA9550-08-1-0384. NR 14 TC 32 Z9 34 U1 1 U2 5 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN-FEB PY 2010 VL 15 IS 1 AR 010512 DI 10.1117/1.3308642 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 586VY UT WOS:000276944200008 PM 20210424 ER PT J AU Palena, C Schlom, J AF Palena, Claudia Schlom, Jeffrey TI Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Article ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; TUMOR-INFILTRATING LYMPHOCYTES; ANTIGEN-PRESENTING CELLS; EPITHELIAL-MESENCHYMAL TRANSITIONS; RESISTANT PROSTATE-CANCER; REGIONAL LYMPH-NODES; MHC CLASS-I; COSTIMULATORY MOLECULES; METASTATIC MELANOMA AB Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression. C1 [Palena, Claudia; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM js141c@nih.gov NR 126 TC 26 Z9 27 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 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2010 AR 380697 DI 10.1155/2010/380697 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 577RA UT WOS:000276240500001 ER PT J AU Vergati, M Intrivici, C Huen, NY Schlom, J Tsang, KY AF Vergati, Matteo Intrivici, Chiara Huen, Ngar-Yee Schlom, Jeffrey Tsang, Kwong Y. TI Strategies for Cancer Vaccine Development SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Review ID TRANSFECTED DENDRITIC CELLS; REFRACTORY PROSTATE-CANCER; HEAT-SHOCK PROTEINS; TUMOR-MESSENGER-RNA; ALLOGENEIC CELLULAR IMMUNOTHERAPY; ACTIVE SPECIFIC IMMUNOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; BLP25 LIPOSOME VACCINE; SIPULEUCEL-T APC8015; PHASE-I/II TRIAL AB Treating cancer with vaccines has been a challenging field of investigation since the 1950s. Over the years, the lack of effective active immunotherapies has led to the development of numerous novel strategies. However, the use of therapeutic cancer vaccines may be on the verge of becoming an effective modality. Recent phase II/III clinical trials have achieved hopeful results in terms of overall survival. Yet despite these encouraging successes, in general, very little is known about the basic immunological mechanisms involved in vaccine immunotherapy. Gaining a better understanding of the mechanisms that govern the specific immune responses (i.e., cytotoxic T lymphocytes, CD4 T helper cells, T regulatory cells, cells of innate immunity, tumor escape mechanisms) elicited by each of the various vaccine platforms should be a concern of cancer vaccine clinical trials, along with clinical benefits. This review focuses on current strategies employed by recent clinical trials of therapeutic cancer vaccines and analyzes them both clinically and immunologically. C1 [Vergati, Matteo; Intrivici, Chiara; Huen, Ngar-Yee; Schlom, Jeffrey; Tsang, Kwong Y.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM js141c@nih.gov NR 101 TC 40 Z9 41 U1 1 U2 8 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 EI 1110-7251 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2010 AR 596432 DI 10.1155/2010/596432 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 638GM UT WOS:000280881500001 ER PT J AU Blees, JS Schmid, T Thomas, CL Baker, AR Benson, L Evans, JR Goncharova, EI Colburn, NH McMahon, JB Henrich, CJ AF Blees, Johanna S. Schmid, Tobias Thomas, Cheryl L. Baker, Alyson R. Benson, Lauren Evans, Jason R. Goncharova, Ekaterina I. Colburn, Nancy H. McMahon, James B. Henrich, Curtis J. TI Development of a High-Throughput Cell-Based Reporter Assay to Identify Stabilizers of Tumor Suppressor Pdcd4 SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE Pdcd4; translation; tumor suppressor; high-throughput assay; natural products ID PROTEIN-KINASE-C; TRANSFORMATION SUPPRESSOR; PROGRAMMED CELL-DEATH-4; SELECTIVE INHIBITOR; COLORECTAL-CANCER; NATURAL-PRODUCTS; TRANSLATION; EXPRESSION; CARCINOMA; PROGRAMMED-CELL-DEATH-4 AB The novel tumor suppressor Pdcd4 affects tumorigenesis by inhibiting translation. Pdcd4 is phosphorylated and subsequently lost by proteasomal degradation in response to tumor-promoting conditions. Here, the authors describe the development of a reporter cell system to monitor the stability of Pdcd4. The phosphorylation-dependent degradation domain ("target") or an adjacent ("off-target") region of Pdcd4 was cloned into a luciferase expression system. The target constructs were responsive to Pdcd4 degrading conditions (e.g., TPA, p70S6K1 overactivation), whereas the off-target constructs remained stable. The system was optimized for and shown to be reliable in a high-throughput compatible 384-well format. Screening of 15,275 pure compounds resulted in a hit rate of 0.30% (>50% inhibition of TPA-induced loss of signal, confirmed by reassay). Among the hits were inhibitors of previously identified critical signaling events for TPA-induced Pdcd4 degradation. One compound was identified to be nonspecific using the off-target control cell line. Screening of 135,678 natural product extracts yielded 42 confirmed, specific hits. Z' averaged 0.58 across 446 plates. Further characterization of active natural products and synthetic compounds is expected to identify novel Pdcd4 stabilizers that may be useful in targeting translation to prevent or treat cancers. (Journal of Biomolecular Screening 2010: 2129) C1 [Henrich, Curtis J.] NCI, SAIC Frederick Inc, Mol Targets Lab, Frederick, MD 21702 USA. [Henrich, Curtis J.] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. [Blees, Johanna S.; Schmid, Tobias] Goethe Univ Frankfurt, Inst Biochem 1, Frankfurt, Germany. [Schmid, Tobias; Baker, Alyson R.; Benson, Lauren; Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick, MD 21702 USA. [Evans, Jason R.; Goncharova, Ekaterina I.] NCI, Data Management Serv, Frederick, MD 21702 USA. RP Henrich, CJ (reprint author), NCI, SAIC Frederick Inc, Mol Targets Lab, Bldg 538,Room 141, Frederick, MD 21702 USA. EM henrichcj@mail.nih.gov RI Benson, Lauren/A-3086-2017 OI Benson, Lauren/0000-0002-7526-273X FU National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or 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, commercial products, or organizations imply endorsement by the US government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 12 Z9 12 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD JAN PY 2010 VL 15 IS 1 BP 21 EP 29 DI 10.1177/1087057109351028 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 544JB UT WOS:000273650900003 PM 19901084 ER PT J AU Follmann, D Fay, M AF Follmann, Dean Fay, Michael TI Exact Inference for Complex Clustered Data Using Within-Cluster Resampling SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Clustering; Correlated data; Multiple outputation; Permutation test; Within-cluster resampling ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERMUTATION TESTS; REGRESSION; TRIALS AB This paper introduces exact permutation methods for use when there are independent clusters of data with arbitrary within-cluster correlation. To eliminate the problem of clustering, we randomly select a data point from each cluster and for this now independent data, and calculate our test statistic and the associated support points for all possible permutations. While clearly valid, this is also inefficient. We repeat this process until all possible independent data sets have been created and use the support points averaged over the randomly created data sets as our reference distribution for the averaged test statistic. This approach uses all of the data and is a permutation extension of within-cluster resampling (WCR). We discuss both exact and Monte Carlo versions of the approach and apply it to several data sets. WCR permutation can be applied in quite general settings when within cluster correlation is a nuisance and exact inference is necessary. C1 [Follmann, Dean; Fay, Michael] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Follmann, D (reprint author), NIAID, Biostat Res Branch, 6700B Rockledge Dr MSC 7609, Bethesda, MD 20892 USA. EM dfollmann@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625 NR 23 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2010 VL 20 IS 4 BP 850 EP 869 AR PII 922421018 DI 10.1080/10543401003618884 PG 20 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 600QX UT WOS:000278003200010 PM 20496210 ER PT J AU Looker, AC Melton, LJ Harris, TB Borrud, LG Shepherd, JA AF Looker, Anne C. Melton, L. Joseph, III Harris, Tamara B. Borrud, Lori G. Shepherd, John A. TI Prevalence and Trends in Low Femur Bone Density Among Older US Adults: NHANES 2005-2006 Compared With NHANES III SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE FEMORAL NECK; OSTEOPOROSIS, TOTAL HIP; RACE/ETHNICITY, GENDER; SECULAR TRENDS ID RACE/ETHNIC DIFFERENCES; MINERAL DENSITY; PENCIL-BEAM; DXA-SYSTEMS; OSTEOPOROSIS; FRACTURES; WOMEN AB Hip fracture incidence appears to be declining in the United States, but changes in bone mineral density (BMD) of the population have not been evaluated. We used femur BMD data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 to estimate the prevalence of low femoral BMD in adults age 50 years and older and compared it with estimates from NHANES III (1988-1994). Dual-energy X-ray absorptiometry systems (pencil-beam geometry in NHANES 111, fan-beam geometry in NHANES 2005-2006) were used to measure femur BMD, and World Health Organization (WHO) definitions of low BMD were used to categorize skeletal status. In 2005-2006, 49% of older US women had osteopenia and 10% had osteoporosis at the femur neck, In men, 30% had femur neck osteopenia and 2% had femur neck osteoporosis. An estimated 5.3 million older men and women had osteoporosis at the femur neck, and 34.5 million more had osteopenia in 2005-2006. When compared with NHANES 111, the age-adjusted prevalence of femur neck osteoporosis in NHANES 2005-2006 was lower in men (by 3 percentage units) and women (by 7 percentage units) overall and among non-Hispanic whites. Changes in body mass index or osteoporosis medication use between surveys did not fully explain the decline in osteoporosis. Owing to the increase in the number of older adults in the US population, however, more older adults had low femur neck BMD (osteoporosis + osteopenia) in 2005-2006 than in 1988-1994. Thus, despite the decline in prevalence, the estimated number of affected older adults in 2005-2006 remained high. (C) 2010 American Society for Bone and Mineral Research. C1 [Looker, Anne C.; Borrud, Lori G.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Melton, L. Joseph, III] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN USA. [Harris, Tamara B.] NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. [Shepherd, John A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Looker, AC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Room 4310,3311 Toledo Rd, Hyattsville, MD 20782 USA. EM Alooker@cdc.gov FU Intramural NIH HHS [ZIA AG004050-04] NR 30 TC 95 Z9 101 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2010 VL 25 IS 1 BP 64 EP 71 DI 10.1359/jbmr.090706 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 555NC UT WOS:000274517600010 PM 19580459 ER PT J AU Guerrero, MA Suh, I Vriens, MR Shen, WT Gosnell, J Kebebew, E Duh, QY Clark, OH AF Guerrero, Marlon A. Suh, Insoo Vriens, Menno R. Shen, Wen T. Gosnell, Jessica Kebebew, Electron Duh, Quan-Yang Clark, Orlo H. TI Age and tumor size predicts lymph node involvement in Hurthle Cell Carcinoma SO JOURNAL OF CANCER LA English DT Article DE Hurthle cell carcinoma; Lymph node metastasis; Age; Tumor size; Prediction AB Introduction: Hurthle cell carcinoma (HCC) is a rare tumor that tends to metastasize to the lymph nodes. Some studies have correlated size of Hurthle cell tumors with the risk of malignancy. Whether the size of HCC correlates with the risk of lymph node (LN) metastases, to our knowledge has not been addressed. Methods: A retrospective analysis was performed on all patients diagnosed with HCC on final pathology between 1997 and 2008. The tumor size and lymph node status was obtained for each patient. The data were analyzed utilizing Student's t-test and the Fisher's exact test to calculate the two-tailed p-value. Results: Out of 39 patients diagnosed with HCC 3(8%) had LN metastases; 1 had ipsilateral central LN metastasis and 2 had ipsilateral central and lateral LN metastasis. LN dissection was performed in patients with known metastasis (2 were evident on preoperative ultrasound and 1 intraoperatively). Patients with LN metastasis were older than those without (mean age: 86.7 and 56.4 years, respectively), had larger tumors (mean size: 6 and 4 cm) and were commonly male (2 of 3). No tumor < 5cm presented with lymph node involvement (3/15 with >5cm cancer had node metastasis, 0/24 with <5cm cancer had node metastasis). Conclusions: Similar to what has been found in patients with papillary thyroid cancer, older male patients with Hurthle cell carcinomas greater than 5cm are more likely to have lymph node metastasis. Our data suggest that these patients may benefit from a prophylactic ipsilateral central neck dissection at the time of their initial operation. C1 [Guerrero, Marlon A.] Univ Arizona, Dept Surg, Tucson, AZ 85724 USA. [Suh, Insoo; Vriens, Menno R.; Shen, Wen T.; Gosnell, Jessica; Duh, Quan-Yang; Clark, Orlo H.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Kebebew, Electron] NCI, Surg Branch, Bethesda, MD 20892 USA. RP Guerrero, MA (reprint author), Univ Arizona, Dept Surg, 1501 N Campbell Ave,4327D, Tucson, AZ 85724 USA. EM mguerrero@surgery.arizona.edu NR 11 TC 9 Z9 9 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2010 VL 1 BP 23 EP 26 PG 4 WC Oncology SC Oncology GA V28QL UT WOS:000208695200004 PM 20842220 ER PT J AU Guerrero, MA Kebebew, E AF Guerrero, Marlon A. Kebebew, Electron TI Adrenocortical Carcinoma and Synchronous Malignancies SO JOURNAL OF CANCER LA English DT Article DE Adrenocortical carcinoma; Ovarian cancer; Uterine cancer; Synchronous malignancies; and Hereditary syndrome AB Objective: Adrenocortical carcinoma (ACC) is an aggressive tumor that accounts for 0.02% of all reported cancers. ACC commonly arises in a sporadic manner, but may also manifest as part of a familial syndrome. Regardless of the setting, ACC rarely arises concurrent with other malignant tumors. Methods: In this report we describe a 32-year-old woman who on work-up for abnormal vaginal bleeding was diagnosed with synchronous uterine adenocarcinoma, ovarian adenocarcinoma and ACC. We also provide a literature review of the past 20 years to identify other patients with ACC and synchronous malignant tumors, and those with familial syndromes associated with an increased risk of developing ACC. Results and Conclusions: To our knowledge this is the first report of a patient with synchronous malignant tumors of the uterus, ovary and adrenal gland. Review of the literature revealed only 5 other cases in which a patient had concurrent ACC and malignant tumors in other organs. C1 [Guerrero, Marlon A.] Univ Arizona, Dept Surg, Tucson, AZ 85724 USA. [Kebebew, Electron] NCI, Bethesda, MD 20892 USA. RP Guerrero, MA (reprint author), Univ Arizona, Dept Surg, 1501 N Campbell Ave,Room 4327D, Tucson, AZ 85724 USA. EM mguerrero@surgery.arizona.edu NR 19 TC 3 Z9 3 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2010 VL 1 BP 108 EP 111 PG 4 WC Oncology SC Oncology GA V28QL UT WOS:000208695200016 PM 20842232 ER PT J AU Mahabadi, AA Truong, QA Schlett, CL Samy, B O'Donnell, CJ Fox, CS Bamberg, F Hoffmann, U AF Mahabadi, Amir A. Truong, Quynh A. Schlett, Christopher L. Samy, Bharat O'Donnell, Christopher J. Fox, Caroline S. Bamberg, Fabian Hoffmann, Udo TI Axial, area and anteroposterior diameter as estimates of Left atrial size using computed tomography of the chest: Comparison with 3-dimensional volume SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Axial area; Electron beam computed tomography (EBCT); Left atrium; Multidetector computed tomography (MDCT); Reproducibility AB BACKGROUND: Left atrial (LA) size has incremental value in risk stratification. OBJECTIVES: We aimed to assess feasibility and reproducibility of 2 quick measures of LA size by chest CT (axial LA area and LA anteroposterior [AP] diameter) by using contrast-enhanced and CT scans. METHODS: We measured LA size in 100 contrast-enhanced 64-slice multidetector CT (MDCT) scans (randomly selected from the ROMICAT collective) by (1) axial LA area at the level of the left ventricular outflow tract and the mitral valve leaflets, (2) AP diameter in 3-chamber view, and (3) 3-dimensional (3D) LA volume by Simpson's methods. We assessed interobserver and intraobserver intraclass correlation coefficient (ICC) for axial LA area and AP diameter as well as their correlation to 3D LA volume. For axial area, feasibility and reproducibility were also determined in 100 non contrast MDCT scans, randomly selected from the Framingham Heart Offspring collective. RESULTS: in contrast-enhanced CT, both LA axial area and AP diameter had excellent reproducibility (interobserver: axial area: ICC, 0.96, mean relative difference, 2.4% +/- 7.4%; AP diameter: ICC, 0.91, 3.6% +/- 7.2%; intraobserver: axial area: ICC, 0.99, 0.4% +/- 5.2%; AP diameter: ICC, 0.94, 1.7% +/- 5.5%). Correlations with 3D volume were better for axial area (r = 0.88) than for AP diameter = 0.67). In non contrast images, axial area could be assessed with excellent reproducibility (interobserver: ICC, 0.96, 0.5% +/- 8.3%; intraobserver: ICC, 0.99, 0.01% +/- 4.4%). CONCLUSION: Both AP diameter and axial LA area permit quick and reproducible estimates of LA volume in contrast-enhanced and non contrast electrocardiographic-gated chest CT. However, LA area should be used preferably over AP diameter because of its better agreement to 3D LA volume. (c) 2010 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Mahabadi, Amir A.; Truong, Quynh A.; Schlett, Christopher L.; Bamberg, Fabian; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Dept Radiol, Boston, MA 02114 USA. [Truong, Quynh A.; O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Samy, Bharat] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Cardiol, Boston, MA 02114 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Mahabadi, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program,Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM amir.mahabadi@stud.uni-due.de FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Institutes of Health (NIH) [R01 HL080053]; German National Academic Foundation; NIH [T32HL076136, L30HL093896]; Federal Ministry of Education and Research; Foundation of German Business, Berlin FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195) and by the National Institutes of Health (NIH) (R01 HL080053). A.A.M. is supported by a grant from the German National Academic Foundation. Q.A.T. has received support from NIH (T32HL076136 and L30HL093896). C.L.S. is supported by grants from the Federal Ministry of Education and Research, and Foundation of German Business, Berlin. NR 23 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JAN-FEB PY 2010 VL 4 IS 1 BP 49 EP 54 DI 10.1016/j.jcct.2009.10.013 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V26BE UT WOS:000208520300009 PM 20159629 ER PT J AU Kurahashi, T Furusawa, T Ueda, T Bustin, M AF Kurahashi, Toshihiro Furusawa, Takashi Ueda, Tetsuya Bustin, Michael TI The Nucleosome Binding Protein HMGN3 Is Expressed in Pancreatic alpha-Cells and Affects Plasma Glucagon Levels in Mice SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE HMGN PROTEINS; GLUCAGON SECRETION; PANCREATIC ISLETS; DIABETES ID CHROMATIN; PHOSPHORYLATION; SOMATOSTATIN; ACTIVATION; SECRETION; INSULIN; GLUT-2 AB Glucose homeostasis requires the coordinated actions of various organs and is critically dependent on the proper functioning of the various cell types present in the pancreatic Langerhans islets. Here we report that chromatin architectural protein HMGN3 is highly expressed in all pancreatic endocrine islet cells, and that Hmgn3-/- mice which have a mild diabetic phenotype, have reduced glucagon levels in their blood. To elucidate the mechanism leading to altered glucagon secretion of Hmgn3-/- mice, we tested whether HMGN3 affect glucagon synthesis and secretion in alpha TC1-9 cells, a glucagon secreting cell line that is used to Study pancreatic a-cell function. We find that in these cells deletion of either HMGN3 or other HMGN variants, does not significantly affect glucagon gene expression or glucagon secretion. Our studies demonstrate a link between HMGN3 and glucagon blood levels that is not directly dependent of the function of pancreatic alpha-cells. J. Cell. Biochem. 109: 49-57, 2010. Published 2009 Wiley-Liss, Inc. C1 [Kurahashi, Toshihiro; Furusawa, Takashi; Ueda, Tetsuya; Bustin, Michael] NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Bustin, Michael/G-6155-2015 FU Japanese Biomedical and Behavioral Research at NIH; Center for Cancer Research; National Cancer Institute, NIH FX This research was supported by a JSPS research fellowship from the Japanese Biomedical and Behavioral Research at NIH to T.K., and by the Center for Cancer Research, the intramural program of the National Cancer Institute, NIH. NR 22 TC 4 Z9 5 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 1 PY 2010 VL 109 IS 1 BP 49 EP 57 DI 10.1002/jcb.22377 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 540NK UT WOS:000273339200007 PM 19885867 ER PT J AU Bobick, BE Tuan, RS Chen, FH AF Bobick, Brent E. Tuan, Rocky S. Chen, Faye H. TI The Intermediate Filament Vimentin Regulates Chondrogenesis of Adult Human Bone Marrow-Derived Multipotent Progenitor Cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE CHONDROGENESIS; MULTIPOTENT PROGENITOR CELL; BONE MARROW STROMA; VIMENTIN; INTERMEDIATE FILAMENT; PROTEIN KINASE A ID MICE LACKING VIMENTIN; GROWTH-FACTOR-BETA; PROTEIN-KINASE-A; HUMAN ARTICULAR CHONDROCYTES; IN-VITRO CHONDROGENESIS; MESENCHYMAL STEM-CELLS; CARTILAGE FORMATION; ACTIN CYTOSKELETON; DIFFERENTIATION; SOX9 AB Cytoskeletal proteins play important regulatory roles in a variety of cellular processes, including proliferation, migration, and differentiation. However, whereas actin and tubulin have established roles regulating developmental chondrogenesis. there is no evidence supporting a function for the intermediate filament vimentin in embryonic cartilage Formation. We hypothesized that vimentin may regulate the chondrogenic differentiation of adult multipotent progenitor cells (MPCs), such as those involved in cartilage formation during bone fracture repair. As Our model of adult progenitor cell chondrogenesis, we employed high-density pellet Cultures of human bone marrow-derived MPCs. siRNA-mediated knockdown of vimentin mRNA and protein triggered a reduction in the extent of MPC cartilage Formation, as evidenced by depressed accumulation of mRNAs for the cartilage-specific marker genes aggrecan and collagen type 11, as well as reduced levels of Alcian blue-stainable proteoglycan and collagen 11 protein in the extracellular matrix. Moreover, mRNA and protein levels for the chondro-regulatory transcription factors SOX5, SOX6, and SOX9 were diminished by vimentin knockdown. Depleted cellular vimentin also induced a drastic reduction in PKA phosphorylation levels but did not affect the phosphorylation of multiple other chondro-regulatory kinases and transcription factors, including ERK1/2, p38, Smad2, and Smad1/5/8. Importantly, siRNA-mediated knockdown of PKA C-alpha mRNA and protein mimicked the reduction in chondrogenesis caused by diminished cellular vimentin. Finally, overexpression of vimentin in MPCs significantly enhanced the activity of a transfected collagen II promoter-luciferase reporter gene. In Conclusion, we describe novel role for the intermediate filament vimentin as a positive regulator of adult human bone marrow-derived MPC chondrogenesis. J. Cell. Biochem. 109: 265-276, 2010. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Chen, Faye H.] NIAMSD, Div Musculoskeletal Dis, NIH, Dept Hlth & Human Serv,Cartilage Biol & Orthopaed, Bethesda, MD 20892 USA. [Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. [Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Pittsburgh, PA 15261 USA. RP Chen, FH (reprint author), NIAMSD, Div Musculoskeletal Dis, NIH, Dept Hlth & Human Serv,Cartilage Biol & Orthopaed, 6701 Democracy Blvd,Room 852, Bethesda, MD 20892 USA. EM chenf1@mail.nih.gov FU Natural Sciences and Engineering Research Council of Canada FX The authors wish to thank Dr. Peter Alexander, Dr. Xibin Wang, Dr. Farida Djouad, and Dr. Lisa Boyette for technical assistance, as well as Dr. Paul Manner (University of Washington) for providing human tissues. Dr. Brent Bobick was supported by a postdoctoral fellowship from the Natural Sciences and Engineering Research Council of Canada. NR 55 TC 12 Z9 14 U1 3 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 1 PY 2010 VL 109 IS 1 BP 265 EP 276 DI 10.1002/jcb.22419 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 540NK UT WOS:000273339200028 PM 19937731 ER PT J AU Wang, P Hou, SX AF Wang, Ping Hou, Steven X. TI Regulation of Intestinal Stem Cells in Mammals and Drosophila SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID MOUSE SMALL INTESTINE; SELF-RENEWAL; BETA-CATENIN; EPITHELIUM; ORIGIN; CANCER; WNT; DIFFERENTIATION; SIGNALS; MIDGUT AB The digestive systems in mammals and Drosophila are quite different in terms of their complexity and organization, but their biological functions are similar. The Drosophila midgut is a functional equivalent of the mouse small intestine. Adult intestinal stem cells (ISCs) have been identified in both the mouse small intestine and Drosophila midgut. The anatomy and cell renewal in the Drosophila midgut are similar to those in the mouse small intestine: the intestinal epithelium in both systems is a tube composed of epithelial cells with absorptive and secretory functions; the Notch signaling controls absorptive versus secretory fate decisions in the intestinal epithelium; cell renewal in both systems starts from stem cells in the basal cell layer, and the differentiated cells then move toward the lumen. However, it is clear that the stem cells in the two systems are regulated in different ways. In this review, we will compare cell renewal and stem cell regulation in the two systems. J. Cell. Physiol. 222: 33-37, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Wang, Ping; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Hou, SX (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. EM hous@mail.nih.gov NR 29 TC 29 Z9 30 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2010 VL 222 IS 1 BP 33 EP 37 DI 10.1002/jcp.21928 PG 5 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 529OY UT WOS:000272528300005 PM 19739102 ER PT J AU Vallejo, G Maschi, D Mestre-Citrinovitz, AC Aiba, K Maronna, R Yohai, V Ko, MSH Beato, M Saragueta, P AF Vallejo, Griselda Maschi, Dario Mestre-Citrinovitz, Ana C. Aiba, Kazuhiro Maronna, Ricardo Yohai, Victor Ko, Minoru S. H. Beato, Miguel Saragueeta, Patricia TI Changes in Global Gene Expression During In Vitro Decidualization of Rat Endometrial Stromal Cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-BETA; EMBRYO IMPLANTATION; EARLY-PREGNANCY; GROWTH-FACTOR; CYCLIN D3; DIFFERENTIATION; MOUSE; PROTEIN; FOLLISTATIN; ACTIVATION AB During the preimplantation phase of pregnancy the endometrial stroma differentiates into decidua, a process that implies numerous morphological changes and is an example of physiological transdifferentiation. Here we show that UIII rat endometrial stromal cells cultured in the presence of calf serum acquired morphological features of decidual cells and expressed decidual markers. To identify genes involved in decidualization we compared gene expression patterns of control and decidualized UIII cells using cDNA microarray. We found 322 annotated genes exhibiting significant differences in expression (>3-fold, fold discovery rate (FDR) >0.005), of which 312 have not been previously related to decidualization. Analysis of overrepresented functions revealed that protein synthesis, gene expression, and chromatin architecture and remodeling are the most relevant modified functions during decidualization. Relevant genes are also found in the functional terms differentiation, cell proliferation, signal transduction, and matrix/structural proteins. Several of these new genes involved in decidualization (Csdc2, Trim27, Eef1a1, Bmp1, Wt1, Aes, Gna12, and Men1) are shown to be also regulated in uterine decidua during normal pregnancy. Thus, the UIII cell culture model will allow future mechanistic studies to define the transcriptional network regulating reprogramming of stromal cells into decidual cells. J. Cell. Physiol. 222: 127-137, 2010. (C) 2009 Wiley-Liss, Inc. C1 [Vallejo, Griselda; Maschi, Dario; Mestre-Citrinovitz, Ana C.; Saragueeta, Patricia] IBYME CONICET, RA-1428 Buenos Aires, DF, Argentina. [Aiba, Kazuhiro; Ko, Minoru S. H.] NIA, Genet Lab, Baltimore, MD 21224 USA. [Maronna, Ricardo] Univ Nacl La Plata, Fac Ciencias Exactas, Dept Matemat, La Plata, Buenos Aires, Argentina. [Yohai, Victor] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Matemat, Buenos Aires, DF, Argentina. [Yohai, Victor] CICPBA, La Plata, Buenos Aires, Argentina. [Beato, Miguel; Saragueeta, Patricia] Univ Pompeu Fabra, Ctr Regulacio Genom, Barcelona, Spain. [Saragueeta, Patricia] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Fisiol & Biol Mol & Celular, Buenos Aires, DF, Argentina. RP Saragueta, P (reprint author), IBYME CONICET, Obligado 2490, RA-1428 Buenos Aires, DF, Argentina. EM sarag@dna.uba.ar RI Ko, Minoru/B-7969-2009; Beato, Miguel/B-5564-2015 OI Ko, Minoru/0000-0002-3530-3015; Beato, Miguel/0000-0002-2878-2222 FU NIH; National Institute on Aging; Agencia Nacional de Promocion Cientifica y Tecnologica, 'Argentina' [PICT 5-34086]; Universidad de Buenos Aires; Consejo Nacional de Investigaciones Cientificas y Tecnicas; CRG; DURST; MEC [BFU2006-10693] FX Contract grant number: BFU2006-10693. NR 68 TC 5 Z9 6 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2010 VL 222 IS 1 BP 127 EP 137 DI 10.1002/jcp.21929 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 529OY UT WOS:000272528300017 PM 19780023 ER PT J AU Elking, DM Cisneros, GA Piquemal, JP Darden, TA Pedersen, LG AF Elking, Dennis M. Cisneros, G. Andres Piquemal, Jean-Philip Darden, Thomas A. Pedersen, Lee G. TI Gaussian Multipole Model (GMM) SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID POLARIZABLE MOLECULAR-MECHANICS; INTERMOLECULAR INTERACTION ENERGY; DENSITY-FUNCTIONAL METHODS; INITIO QUANTUM-CHEMISTRY; CLASSICAL FORCE-FIELDS; FLUCTUATING CHARGE; INTEGRAL EVALUATION; CONFORMATIONAL DEPENDENCE; ELECTROSTATIC POTENTIALS; DYNAMICS SIMULATIONS AB An electrostatic model based on charge density is proposed as a model for future force fields. The model is composed of a nucleus and a single Slater-type contracted Gaussian multipole charge density on each atom. The Gaussian multipoles are fit to the electrostatic potential calculated at the B3LYP/6-31G(star) and HF/aug-cc-pVTZ levels of theory and tested by comparing electrostatic dimer energies, intermolecular density overlap integrals, and permanent molecular multipole moments with their respective ab initio values. For the case of water, the atomic Gaussian multipole moments Q(tm) are shown to be a smooth function of internal geometry (bond length and angle), which can be approximated by a truncated linear Taylor series. In addition, results are given when the Gaussian multipole charge density is applied to a model for exchange-repulsion energy based on the intermolecular density overlap. C1 [Elking, Dennis M.; Cisneros, G. Andres; Darden, Thomas A.; Pedersen, Lee G.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Piquemal, Jean-Philip] Univ Paris 06, CNRS, UMR 7616, Chim Theor Lab, F-75252 Paris, France. [Pedersen, Lee G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Pedersen, LG (reprint author), NIEHS, Struct Biol Lab, POB 12233,MD K3-16, Res Triangle Pk, NC 27709 USA. EM lee_pedersen@unc.edu RI pedersen, lee/A-8567-2009; Cisneros, Gerardo/B-3128-2010; Piquemal, Jean-Philip/B-9901-2009; Pedersen, Lee/E-3405-2013 OI Piquemal, Jean-Philip/0000-0001-6615-9426; Pedersen, Lee/0000-0003-1262-9861 FU National Institute of Health (NIH) [L06350]; National Institute of Environmental Health Sciences [Z01 ES9043010-23]; National Science Foundation Focused Research Groups, Department of Materials Research [0804549] FX This research was supported in part by the Intramural Research Program of the National Institute of Health (NIH) and the National Institute of Environmental Health Sciences (Z01 ES9043010-23). L.G.P. acknowledges from the National Science Foundation Focused Research Groups, Department of Materials Research 0804549 and from the NIH L06350. We would like to thank the reviewers for their helpful comments, which improved the Manuscript. NR 83 TC 42 Z9 42 U1 0 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD JAN PY 2010 VL 6 IS 1 BP 190 EP 202 DI 10.1021/ct900348b PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 558PN UT WOS:000274757000020 PM 20209077 ER PT J AU Spjuth, O Willighagen, EL Guha, R Eklund, M Wikberg, JES AF Spjuth, Ola Willighagen, Egon L. Guha, Rajarshi Eklund, Martin Wikberg, Jarl E. S. TI Towards interoperable and reproducible QSAR analyses: Exchange of datasets SO JOURNAL OF CHEMINFORMATICS LA English DT Article AB Background: QSAR is a widely used method to relate chemical structures to responses or properties based on experimental observations. Much effort has been made to evaluate and validate the statistical modeling in QSAR, but these analyses treat the dataset as fixed. An overlooked but highly important issue is the validation of the setup of the dataset, which comprises addition of chemical structures as well as selection of descriptors and software implementations prior to calculations. This process is hampered by the lack of standards and exchange formats in the field, making it virtually impossible to reproduce and validate analyses and drastically constrain collaborations and reuse of data. Results: We present a step towards standardizing QSAR analyses by defining interoperable and reproducible QSAR datasets, consisting of an open XML format (QSAR-ML) which builds on an open and extensible descriptor ontology. The ontology provides an extensible way of uniquely defining descriptors for use in QSAR experiments, and the exchange format supports multiple versioned implementations of these descriptors. Hence, a dataset described by QSAR-ML makes its setup completely reproducible. We also provide a reference implementation as a set of plugins for Bioclipse which simplifies setup of QSAR datasets, and allows for exporting in QSAR-ML as well as old-fashioned CSV formats. The implementation facilitates addition of new descriptor implementations from locally installed software and remote Web services; the latter is demonstrated with REST and XMPP Web services. Conclusions: Standardized QSAR datasets open up new ways to store, query, and exchange data for subsequent analyses. QSAR-ML supports completely reproducible creation of datasets, solving the problems of defining which software components were used and their versions, and the descriptor ontology eliminates confusions regarding descriptors by defining them crisply. This makes is easy to join, extend, combine datasets and hence work collectively, but also allows for analyzing the effect descriptors have on the statistical model's performance. The presented Bioclipse plugins equip scientists with graphical tools that make QSAR-ML easily accessible for the community. C1 [Spjuth, Ola; Willighagen, Egon L.; Eklund, Martin; Wikberg, Jarl E. S.] Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden. [Guha, Rajarshi] NIH, Chem Genom Ctr, Rockville, MD 20850 USA. RP Spjuth, O (reprint author), Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden. EM ola.spjuth@farmbio.uu.se RI Willighagen, Egon/C-6136-2008; OI Willighagen, Egon/0000-0001-7542-0286; Spjuth, Ola/0000-0002-8083-2864 FU Swedish VR [04X-05957]; Uppsala University [KoF 07] FX This work was supported by the Swedish VR (04X-05957) and Uppsala University (KoF 07). NR 42 TC 23 Z9 23 U1 0 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-2946 J9 J CHEMINFORMATICS JI J. Cheminformatics PY 2010 VL 2 AR 5 DI 10.1186/1758-2946-2-5 PG 7 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA V21QN UT WOS:000208222200004 PM 20591161 ER PT J AU Faden, VB Ruffin, B Newes-Adeyi, G Chen, C AF Faden, Vivian B. Ruffin, Beverly Newes-Adeyi, Gabriella Chen, Chiung TI The Relationship among Pubertal Stage, Age, and Drinking in Adolescent Boys and Girls SO JOURNAL OF CHILD & ADOLESCENT SUBSTANCE ABUSE LA English DT Article DE adolescence; alcohol; puberty ID IV ALCOHOL-ABUSE; DEPRESSIVE SYMPTOMS; SEXUAL-MATURATION; ONSET; DEPENDENCE; CIGARETTE; PATTERN AB This study used data from the Third National Household and Nutrition Examination Survey ( NHANES) to examine the association between pubertal status ( Tanner staging for boys and girls and menarche for girls) and alcohol use in a nationally representative sample of youths ages 12 to 17. Logistic regression was used to model the relationship. In general, more advanced pubertal stage was associated with a greater likelihood of having had at least 12 drinks in one's life. In particular, among 12- to 13-year-old boys and girls, higher Tanner scores were associated with increased risk for having already had at least 12 drinks in one's life. Thus, early puberty is associated with having initiated drinking at a young age and therefore may be a marker to help identify a group of youths with whom intervening early regarding alcohol use may be particularly useful. C1 [Faden, Vivian B.] NIAAA, Off Sci Policy & Commun, Bethesda, MD 20892 USA. [Newes-Adeyi, Gabriella; Chen, Chiung] CSR Inc, Arlington, VA USA. RP Faden, VB (reprint author), NIAAA, Off Sci Policy & Commun, 5635 Fishers Lane,Room 2087, Bethesda, MD 20892 USA. EM vfaden@mail.nih.gov NR 33 TC 1 Z9 1 U1 1 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1067-828X J9 J CHILD ADOLES SUBST JI J. Child Adolesc. Subst. Abus. PY 2010 VL 19 IS 1 BP 1 EP 15 DI 10.1080/10678280903185591 PG 15 WC Substance Abuse SC Substance Abuse GA 547FU UT WOS:000273872700001 ER PT J AU Stringaris, A Santosh, P Leibenluft, E Goodman, R AF Stringaris, Argyris Santosh, Paramala Leibenluft, Ellen Goodman, Robert TI Youth meeting symptom and impairment criteria for mania-like episodes lasting less than four days: an epidemiological enquiry SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Bipolar disorder; manic episodes; attention deficit hyperactivity disorder; oppositional defiant disorder; conduct disorder ID BIPOLAR SPECTRUM DISORDERS; SCHOOL-AGED CHILDREN; DIFFICULTIES QUESTIONNAIRE; PSYCHIATRIC-DISORDERS; PSYCHOMETRIC PROPERTIES; PREVALENCE; ADOLESCENTS; STRENGTHS; PHENOMENOLOGY; ADULTS AB Background: Little is known about short-duration episodes of mania-like symptoms in youth. Here we determine the prevalence, morbid associations, and contribution to social impairment of a phenotype characterised by episodes during which symptom and impairment criteria for mania are met, but DSM-IV duration criteria are not (bipolar not otherwise specified; BP-NOS). Methods: A cross-sectional national survey of a sample (N = 5,326) of 8-19-year-olds from the general population using information from parents and youth. Outcome measures were prevalence rates and morbid associations assessed by the Developmental and Well-Being Assessment, and social impairment assessed by the impact scale of the Strengths and Difficulties Questionnaire. Results: While only seven individuals (.1%) met definite or probable DSM-IV criteria for BPI or BPII, the prevalence of BP-NOS was 10-fold higher, 1.1% by parent report and 1.5% by youth report. Parent-youth agreement was very low: kappa = .02, p > .05 for BP-NOS. Prevalence and episode duration for BP-NOS did not vary by age. BP-NOS showed strong associations with externalising disorders. After adjusting for a dimensional measure of general psychopathology, self-reported (but not parent-reported) BP-NOS remained associated with overall social impairment. Conclusions: BP meeting full DSM-IV criteria is rare in youth. BP-NOS, defined by episodes shorter than those required by DSM-IV, but during which DSM-IV symptom and impairment criteria are met, is commoner and may be associated with social impairment that is beyond what can be accounted for by other psychopathology. These findings support the importance of research into these short episodes during which manic symptoms are met in youth but they also call into question the extent to which BP-NOS in youth is a variant of DSM-IV BP - superficially similar symptoms may not necessarily imply deeper similarities in aetiology or treatment response. C1 [Stringaris, Argyris; Goodman, Robert] Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, London SE5 8AF, England. [Santosh, Paramala] Great Ormond St Hosp Sick Children, Dept Child & Adolescent Mental Hlth, London WC1N 3JH, England. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Stringaris, A (reprint author), Kings Coll London, Inst Psychiat, Dept Child & Adolescent Psychiat, P085,Denmark Hill, London SE5 8AF, England. EM argyris.stringaris@kcl.ac.uk FU Department of Health of the British government FX This study was funded by the Department of Health of the British government. NR 39 TC 35 Z9 35 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JAN PY 2010 VL 51 IS 1 BP 31 EP 38 DI 10.1111/j.1469-7610.2009.02129.x PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 530FW UT WOS:000272575500004 PM 19686330 ER PT J AU Concheiro, M Jones, H Johnson, RE Shakleya, DM Huestis, MA AF Concheiro, Marta Jones, Hendree Johnson, Rolley E. Shakleya, Diaa M. Huestis, Marilyn A. TI Confirmatory analysis of buprenorphine, norbuprenorphine, and glucuronide metabolites in plasma by LCMSMS. Application to umbilical cord plasma from buprenorphine-maintained pregnant women SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Buprenorphine; Plasma; LCMSMS; Umbilical cord plasma ID TANDEM MASS-SPECTROMETRY; LC-MS-MS; HUMAN URINE; GAS-CHROMATOGRAPHY; DEALKYLATED METABOLITE; HAIR SAMPLES; IN-VIVO; BLOOD; QUANTIFICATION; VALIDATION AB An LCMSMS method was developed and fully validated for the simultaneous quantification of buprenorphine (BLIP), norbuprenorphine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) in 0.5 mL plasma, fulfilling confirmation criteria with two transitions for each compound with acceptable relative ion intensities. Transitions monitored were 468.3 > 396.2 and 468.3 > 414.3 for BUP, 414.3 > 340.1 and 414.3 > 326.0 for NBUP, 644.3 > 468.1 and 644.3 > 396.3 for BUP-Gluc, and 590.3 > 414.3 and 590.3 > 396.2 for NBUP-Gluc. Linearity was 0.1-50 ng/mL for BUP and BUP-Gluc, and 0.5-50 ng/mL for NBUP and NBUP-Gluc. Intra-day,inter-day. and total assay imprecision (%RSD) were < 16.8%, and analytical recoveries were 88.6-108.7%. Extraction efficiencies ranged from 71.1 to 87.1%, and process efficiencies 48.7 to 127.7%. All compounds showed ion enhancement, except BUP-Gluc that demonstrated ion suppression: variation between 10 different blank plasma specimens was < 9.1%. In Six umbilical cord plasma specimens from opioid-dependent pregnant women receiving 14-24 mg/day BUP, NBUP-Gluc was the predominant metabolite (29.8 +/- 7.6 ng/mL), with BUP-Gluc (4.6 +/- 4.8 ng/mL). NBUP (1.5 +/- 0.8 ng/mL) and BUP (0.4 +/- 0.2 ng/mL). Although BUP biomarkers can be quantified in umbilical cord plasma in low ng/mL concentrations, the significance of these data as predictors of neonatal outcomes is currently unknown. (C) 2009 Elsevier B.V. All rights reserved. C1 [Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Chem & Drug Metab Intramural Res Program, NIH, BRC, Baltimore, MD 21224 USA. [Jones, Hendree; Johnson, Rolley E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. [Jones, Hendree] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Chem & Drug Metab Intramural Res Program, NIH, BRC, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institutes of Health, National Institute on Drug Abuse FX This research was supported by the National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse. NR 55 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 1 PY 2010 VL 878 IS 1 BP 13 EP 20 DI 10.1016/j.jchromb.2009.11.005 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 543ZT UT WOS:000273621400003 PM 19945361 ER PT J AU Louiset, E Gobet, F Libe, R Horvath, A Renouf, S Cariou, J Rothenbuhler, A Bertherat, J Clauser, E Grise, P Stratakis, CA Kuhn, JM Lefebvre, H AF Louiset, Estelle Gobet, Francoise Libe, Rossella Horvath, Anelia Renouf, Sylvie Cariou, Juliette Rothenbuhler, Anya Bertherat, Jerome Clauser, Eric Grise, Philippe Stratakis, Constantine A. Kuhn, Jean-Marc Lefebvre, Herve TI ACTH-Independent Cushing's Syndrome with Bilateral Micronodular Adrenal Hyperplasia and Ectopic Adrenocortical Adenoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROTEIN-KINASE-A; CARNEY COMPLEX; REST TUMOR; CORTISOL SECRETION; PHOSPHODIESTERASE; DISEASE; PATIENT; MUTATIONS; RECEPTORS; DEXAMETHASONE AB Context: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing's syndrome. Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. Main Outcome Measure: Detection of 17 alpha-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. Results: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17 alpha-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. Conclusion: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing's syndrome. (J Clin Endocrinol Metab 95: 18-24, 2010) C1 [Louiset, Estelle; Renouf, Sylvie; Kuhn, Jean-Marc; Lefebvre, Herve] Univ Rouen, INSERM, Inst Federatif Rech Multidisciplinaires Peptides, Unite 982,Equipe Associee 4310,Lab Neuronal & Neu, F-76821 Mont St Aignan, France. [Gobet, Francoise] Univ Rouen, Univ Hosp Rouen, Inst Biomed Res, Dept Pathol, F-76031 Rouen, France. [Libe, Rossella; Bertherat, Jerome] Univ Paris 05, AP HP, Inst Cochin,Unite Mixte Rech 8104, CNRS,Dept Endocrinol Metab Canc,INSERM,U567, F-75014 Paris, France. [Horvath, Anelia; Rothenbuhler, Anya; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Clauser, Eric] Cochin Hosp, Oncogenet Unit, F-75014 Paris, France. [Kuhn, Jean-Marc; Lefebvre, Herve] Univ Rouen, Rouen Univ Hosp, Dept Endocrinol, Inst Biomed Res, F-76031 Rouen, France. [Cariou, Juliette; Grise, Philippe] Univ Rouen, Rouen Univ Hosp, Dept Urol, Inst Biomed Res, F-76031 Rouen, France. RP Lefebvre, H (reprint author), Univ Rouen, Rouen Univ Hosp, Dept Endocrinol, Inst Biomed Res, F-76031 Rouen, France. EM herve.lefebvre@chu-rouen.fr FU Institut National de la Sante et de la Recherche Medicale Unite [413/EA4310]; Institut Federatif de Recherches Multidisciplinaires sur les Peptides [23]; Carney Complex Network [ANR-08-GENOPAT-007]; Centre Hospitalier Universitaire de Rouen; Reseau COMETE [PHRC AOM 06 179]; Conseil Regional de Haute-Normandie; Agence Nationale de la Recherche [ANR-08-GENOPAT-007] FX This work was supported by Institut National de la Sante et de la Recherche Medicale Unite 413/EA4310, Institut Federatif de Recherches Multidisciplinaires sur les Peptides 23, the Carney Complex Network (ANR-08-GENOPAT-007), the Centre Hospitalier Universitaire de Rouen, the Reseau COMETE (PHRC AOM 06 179), and the Conseil Regional de Haute-Normandie.; Disclosure Summary: E. L., F. G., R. L., A. H., S. R., J. C., A. R., E. C., P. G., C. S., and J.-M. K. have nothing to declare. J. B. and H. L. received grants from Agence Nationale de la Recherche (ANR-08-GENOPAT-007). NR 27 TC 11 Z9 13 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2010 VL 95 IS 1 BP 18 EP 24 DI 10.1210/jc.2009-0881 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541CV UT WOS:000273391300004 PM 19915020 ER PT J AU Lenders, JWM Pacak, K Huynh, TT Sharabi, Y Mannelli, M Bratslavsky, G Goldstein, DS Bornstein, SR Eisenhofer, G AF Lenders, Jacques W. M. Pacak, Karel Huynh, Thanh-Truc Sharabi, Yehonatan Mannelli, Massimo Bratslavsky, Gennady Goldstein, David S. Bornstein, Stefan R. Eisenhofer, Graeme TI Low Sensitivity of Glucagon Provocative Testing for Diagnosis of Pheochromocytoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLASMA-CATECHOLAMINES; BIOCHEMICAL-DIAGNOSIS; METANEPHRINES; RESPONSES; URINE AB Context: Pheochromocytomas can usually be confirmed or excluded using currently available biochemical tests of catecholamine excess. Follow-up tests are, nevertheless, often required to distinguish false-positive from true-positive results. The glucagon stimulation test represents one such test; its diagnostic utility is, however, unclear. Objective: The aim of the study was to determine the diagnostic power of the glucagon test to exclude or confirm pheochromocytoma. Design, Setting, and Subjects: Glucagon stimulation tests were carried out at three specialist referral centers in 64 patients with pheochromocytoma, 38 patients in whom the tumor was excluded, and in a reference group of 36 healthy volunteers. Main Outcome Measures: Plasma concentrations of norepinephrine and epinephrine were measured before and after glucagon administration. Several absolute and relative test criteria were used for calculating diagnostic sensitivity and specificity. Expression of the glucagon receptor was examined in pheochromocytoma tumor tissue from a subset of patients. Results: Larger than 3-fold increases in plasma norepinephrine after glucagon strongly predicted the presence of a pheochromocytoma (100% specificity and positive predictive value). However, irrespective of the various criteria examined, glucagon-provoked increases in plasma catecholamines revealed the presence of the tumor in less than 50% of affected patients. Diagnostic sensitivity was particularly low in patients with pheochromocytomas due to von Hippel-Lindau syndrome. Tumors from these patients showed no significant expression of the glucagon receptor. Conclusion: The glucagon stimulation test offers insufficient diagnostic sensitivity for reliable exclusion or confirmation of pheochromocytoma. Because of this and the risk of hypertensive complications, the test should be abandoned in routine clinical practice. (J Clin Endocrinol Metab 95: 238-245, 2010) C1 [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 GA Nijmegen, Netherlands. [Pacak, Karel; Huynh, Thanh-Truc] NICHHD, Sect Reprod Biol, Bethesda, MD 20892 USA. [Pacak, Karel; Huynh, Thanh-Truc] NICHHD, Med Branch, Bethesda, MD 20892 USA. [Goldstein, David S.] NINDS, Ctr Canc Res, NCI, NIH, Bethesda, MD 20892 USA. [Bratslavsky, Gennady] NINDS, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. [Mannelli, Massimo] Univ Florence, Dept Clin Pathophysiol, I-50014 Florence, Italy. [Sharabi, Yehonatan] Chaim Sheba Med Ctr, Hypertens Unit, IL-52621 Tel Hashomer, Israel. [Lenders, Jacques W. M.; Bornstein, Stefan R.; Eisenhofer, Graeme] Univ Hosp Carl Gustav Carus Dresden, Dept Internal Med 3, D-01307 Dresden, Germany. RP Lenders, JWM (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, Geert Grootepl Zuid 8, NL-6525 GA Nijmegen, Netherlands. EM j.lenders@aig.umcn.nl RI Lenders, J.W.M./L-4487-2015; OI Mannelli, Massimo/0000-0002-8001-9857 NR 25 TC 11 Z9 13 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2010 VL 95 IS 1 BP 238 EP 245 DI 10.1210/jc.2009-1850 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541CV UT WOS:000273391300033 PM 19897672 ER PT J AU Skarulis, MC Celi, FS Mueller, E Zemskova, M Malek, R Hugendubler, L Cochran, C Solomon, J Chen, C Gorden, P AF Skarulis, Monica C. Celi, Francesco S. Mueller, Elisabetta Zemskova, Marina Malek, Rana Hugendubler, Lynne Cochran, Craig Solomon, Jeffrey Chen, Clara Gorden, Phillip TI Thyroid Hormone Induced Brown Adipose Tissue and Amelioration of Diabetes in a Patient with Extreme Insulin Resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SKELETAL-MUSCLE; ENERGY-EXPENDITURE; GLUCOSE; FAT; NORADRENALINE; MECHANISMS; IDENTIFICATION; ADIPOCYTES; TRANSPORT; RECEPTOR AB Context: Brown adipose tissue (BAT) found by positron emission/computed tomography (PET-CT) using flouro-deoxyglucose (FDG) is inducible by cold exposure in men. Factors leading to increased BAT are of great interest for its potential role in the treatment of diabetes and obesity. Objective: We tested whether thyroid hormone (TH) levels are related to the volume and activity of BAT in a patient with a mutation in the insulin receptor gene. Design/Setting/Intervention: Our work was based on the case report of a patient in an observational study at the National Institutes of Health. Patient: The patient discontinued insulin and oral antidiabetics after thyroidectomy and suppressive-dose levothyroxine therapy for thyroid cancer. PET-CT uptake in BAT was confirmed by histology and molecular analysis. Outcomes: PET-CT studies were performed, and we measured hemoglobin A1c and resting energy expenditure before and after levothyroxine discontinuation for thyroid cancer testing. Molecular studies of BAT and white adipose samples are presented. Result: Supraclavicular and periumbilical sc adipose tissue demonstrated molecular features of BAT including uncoupling protein-1, type 2 deiodinase, and PR domain containing 16 by quantitative PCR. Activity of type 2 deiodinase activity was increased. The discontinuation of levothyroxine resulted in decreased FDG uptake and diminished volume of BAT depots accompanied by worsening of diabetic control. Conclusions: This case demonstrates the TH effect on BAT activity and volume in this patient and an association between BAT activity and glucose levels in this patient. Because the contribution of TH on skeletal muscle energy expenditure and fuel metabolism was not assessed, an association between BAT activity and glucose homeostasis can only be suggested. (J Clin Endocrinol Metab 95: 256-262, 2010) C1 [Skarulis, Monica C.; Celi, Francesco S.; Zemskova, Marina; Malek, Rana; Cochran, Craig; Gorden, Phillip] NIDDKD, Clin Endocrine Branch, Bethesda, MD 20892 USA. [Mueller, Elisabetta; Hugendubler, Lynne] NIDDKD, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. [Solomon, Jeffrey] Med Numer, Germantown, MD 20876 USA. [Cochran, Craig] NIH, Imaging Sci Program, Ctr Clin, Bethesda, MD 20892 USA. RP Skarulis, MC (reprint author), 10 Ctr Dr,Bldg 10 CRC,Room 6-3940, Bethesda, MD 20892 USA. EM monica_skarulis@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases [Z01 DK075005-04, Z01-DK047057-01] FX This work was supported by intramural National Institute of Diabetes and Digestive and Kidney Diseases Grants Z01 DK075005-04 and Z01-DK047057-01. NR 28 TC 78 Z9 80 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2010 VL 95 IS 1 BP 256 EP 262 DI 10.1210/jc.2009-0543 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541CV UT WOS:000273391300035 PM 19897683 ER PT J AU Pereira, AM Hes, FJ Horvath, A Woortman, S Greene, E Bimpaki, E Alatsatianos, A Boikos, S Smit, JW Romijn, JA Nesterova, M Stratakis, CA AF Pereira, Alberto M. Hes, Frederik J. Horvath, Anelia Woortman, Sanne Greene, Elizabeth Bimpaki, Eirini Alatsatianos, Anton Boikos, Sosipatros Smit, Johannes W. Romijn, Johannes A. Nesterova, Maria Stratakis, Constantine A. TI Association of the M1V PRKAR1A Mutation with Primary Pigmented Nodular Adrenocortical Disease in Two Large Families SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SUBUNIT TYPE 1A; DEPENDENT PROTEIN-KINASE; CARNEY COMPLEX; REGULATORY SUBUNIT; CUSHINGS-SYNDROME; A PKA; GENE; ENDOCRINE; TUMORS; TISSUES AB Background: Carney complex (CNC) is a familial multiple neoplasia syndrome frequently associated with primary pigmented nodular adrenocortical disease (PPNAD), a bilateral form of micronodular adrenal hyperplasia that leads to Cushing's syndrome (CS). Germline PRKAR1A mutations cause CNC and only rarely isolated PPNAD. Patients and Methods: PRKAR1A mutation analysis in two large families with CS and no other CNC manifestations demonstrated a M1V germline mutation; a total of 21 asymptomatic individuals were screened, and mutation carriers were evaluated for CNC. The mutation was expressed in vitro and functionally tested for its effects on protein kinase A function. Results: Presymptomatic testing identified five first-degree relatives who were M1V carriers and who were all diagnosed with subclinical, mild CS at ages ranging from 20-56 yr. There were no other signs of CNC. In a cell-free system, we detected a shorter compared with the wild-type type 1 alpha regulatory subunit of protein kinase A (PRKAR1A) protein (43 kDa). This was not identified in cell lines from the patients or in transfection experiments in HEK293 cells that showed no detectable PRKAR1A protein from the M1V-bearing constructs. In these cells, the mutant mRNA was expressed in a 1: 1 ratio. Conclusion: In two large families, the M1V PRKAR1A mutation resulted in a PPNAD-only phenotype with significant variability both in terms of age of onset and clinical severity. Expression studies showed a unique effect of this sequence change. This study has implications for genetic counseling of carriers of this PRKAR1A mutation and patients with CNC and PPNAD and for the study of PRKAR1A-related tumorigenesis. (J Clin Endocrinol Metab 95: 338-342, 2010) C1 [Pereira, Alberto M.; Smit, Johannes W.; Romijn, Johannes A.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab, NL-2300 RC Leiden, Netherlands. [Hes, Frederik J.; Woortman, Sanne] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, NL-2300 RC Leiden, Netherlands. [Horvath, Anelia; Greene, Elizabeth; Bimpaki, Eirini; Alatsatianos, Anton; Boikos, Sosipatros; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Horvath, A (reprint author), NICHHD, SEGEN Program Dev Endocrinol & Genet, NIH, CRC, Bldg 10,Room I-3330 E Labs,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM horvatha@mail.nih.gov FU NICHD [Z01-HD-000642-04] FX This work was supported in part by the NICHD, intramural NIH Project Z01-HD-000642-04 to C. A. S. NR 22 TC 12 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2010 VL 95 IS 1 BP 338 EP 342 DI 10.1210/jc.2009-0993 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541CV UT WOS:000273391300048 PM 19915019 ER PT J AU Chini, F Rossi, PG Costantini, M Beccaro, M Borgia, P AF Chini, F. Rossi, P. Giorgi Costantini, M. Beccaro, M. Borgia, P. TI Validity of caregiver-reported hospital admission in a study on the quality of care received by terminally ill cancer patients SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Caregiver reports; Terminal care; Accuracy of recall; Patient admissions; Agreement; Medical records ID EVENTS; AGREEMENT; SERVICES; RECALL; TIME; LIFE AB Background: The clinical status of terminally ill patients often makes it impossible for them to report information directly, which indicates the need to rely oil information from indirect Sources, Such as from caregivers. This information needs to be validated, and particular attention must be given to the accuracy of recall. Objective: The objective of this study is to evaluate the agreement between caregiver-reported hospital admissions with the data reported in the regional hospital information system. Methods: A two-level probabilistic sample of cancer deaths from the ISDOC (Italian Survey oil Dying of Cancer). For the 2,000 deceased sampled, hospitalizations were identified from the administrative data and reported by the caregivers Via a questionnaire. We calculated Cohen's kappa, sensitivity and specificity using the regional archives as the gold standard. A multivariate analysis was performed to assess possible variables that may influence agreement. Results: We interviewed 1,271 caregivers. Sensitivity and specificity were, respectively, 82% (95% confidence interval [CI] = 79-84) and 65% (95% CI = 60-69). Kappa statistic was 0.46 (95% CI = 0.40-0.52). Multivariate analysis showed that agreement increases with educational level and caregiver age. Conclusion: The validation of caregiver's recall for medical procedures has important implications for research and care. because often it is the only information source we can rely on. The questionnaire showed good sensitivity and poor specificity concerning real hospitalizations, and had moderate degree of agreement with the data reported in the administrative data. (C) 2010 Elsevier Inc. All rights reserved. C1 [Chini, F.; Rossi, P. Giorgi; Borgia, P.] Agcy Publ Hlth, I-00198 Rome, Italy. [Costantini, M.; Beccaro, M.] Natl Canc Inst, Clin Epidemiol Unit, Genoa, Italy. RP Chini, F (reprint author), Agcy Publ Hlth, Via S Costanza 53, I-00198 Rome, Italy. EM chini@asplazio.it RI costantini, massimo/G-1443-2012; Giorgi Rossi, Paolo/K-6367-2016; OI Giorgi Rossi, Paolo/0000-0001-9703-2460; costantini, massimo/0000-0002-5293-7079 NR 16 TC 2 Z9 2 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JAN PY 2010 VL 63 IS 1 BP 103 EP 108 DI 10.1016/j.jclinepi.2009.02.006 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 537ZG UT WOS:000273152600015 PM 19447582 ER PT J AU Ostchega, Y Nwankwo, T Sorlie, PD Wolz, M Zipf, G AF Ostchega, Yechiam Nwankwo, Tatiana Sorlie, Paul D. Wolz, Michael Zipf, George TI Assessing the Validity of the Omron HEM-907XL Oscillometric Blood Pressure Measurement Device in a National Survey Environment SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID US DEMOGRAPHIC-TRENDS; MIDARM CIRCUMFERENCE; SPHYGMOMANOMETER; HEALTH; CUFFS AB Blood pressure (BP) readings taken by Omron HEM-907XL were compared with the results obtained using sphygmomanometer (HgS) in 509 individuals using 2002 Association for the Advancement of Medical Instrumentation (AAMI) criteria. With the exception of diastolic BP in youth ages 13 to 19 years (mean difference, -1.77 mm Hg; standard deviation, 8.65), the Omron device met the criteria. Agreement for hypertension (BP >= 140/90 mm Hg) was above chance (kappa=0.68) and, compared with HgS, Omron underestimated the prevalence of hypertension by 2.65%. The Omron and HgS measurements were highly correlated (r=0.94 for systolic BP and r=0.83 for diastolic BP). Both increased systolic and diastolic BP decreased device agreement (beta-coefficient=-0.10872, P <.0001; beta-coefficient=-0.25981, P <.0001, respectively). The Omron device meets AAMI criteria with the exception of diastolic BP in youth ages 13 to 19 years. However, Omron underestimated the prevalence of hypertension and device agreement decreases with increased systolic and diastolic BP. C1 [Ostchega, Yechiam; Nwankwo, Tatiana; Zipf, George] Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Sorlie, Paul D.; Wolz, Michael] NHLBI, NIH, Rockville, MD USA. RP Ostchega, Y (reprint author), Toledo Rd Room 4319, Hyattsville, MD 20782 USA. EM yxo1@cdc.gov FU National Heart, Lung and Blood Institute; National Center for Health Statistics FX Acknowledgments and disclosures: The authors would like to express their gratitude to all involved and who made it possible to complete this validation study. They thank Carlene Grim, from Shared Care, Inc, and Dr Grace Willard, Doe Knight, Gunda Kube, Ruth Pressley, Jaimie Saltzer, and Belma Ybarra, from Westat, Inc. This validation study was supported by the National Heart, Lung and Blood Institute and the National Center for Health Statistics. The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. NR 16 TC 29 Z9 29 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JAN PY 2010 VL 12 IS 1 BP 22 EP 28 DI 10.1111/j.1751-7176.2009.00199.x PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 538DJ UT WOS:000273164100005 PM 20047626 ER PT J AU Kovacic, JC Gupta, R Lee, AC Ma, MC Fang, F Tolbert, CN Walts, AD Beltran, LE San, H Chen, GB St Hilaire, C Boehm, M AF Kovacic, Jason C. Gupta, Rohit Lee, Angela C. Ma, Mingchao Fang, Fang Tolbert, Claire N. Walts, Avram D. Beltran, Leilani E. San, Hong Chen, Guibin St Hilaire, Cynthia Boehm, Manfred TI Stat3-dependent acute Rantes production in vascular smooth muscle cells modulates inflammation following arterial injury in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; INTERFERON REGULATORY FACTOR-1; CARDIOVASCULAR RISK MARKERS; ATHEROSCLEROSIS-PRONE MICE; DEPENDENT KINASE INHIBITOR; NEOINTIMA FORMATION; MONOCYTE RECRUITMENT; TRANSCRIPTION FACTOR; P-SELECTIN AB Inflammation is a key component of arterial injury, with VSMC proliferation and neointimal formation serving as the final outcomes of this process. However, the acute events transpiring immediately after arterial injury that establish the blueprint for this inflammatory program are largely unknown. We therefore studied these events in mice and found that immediately following arterial injury, medial VSMCs upregulated Rantes in an acute manner dependent on Stat3 and NF-kappa B (p65 subunit). This led to early T cell and macrophage recruitment, processes also under the regulation of the cyclin-dependent kinase inhibitor p21(Cip1). Unique to VSMCs, Rantes production was initiated by Tnf-alpha, but not by Il-6/gp130. This Rantes production was dependent on the binding of a p65/Stat3 complex to NF-kappa B-binding sites within the Rantes promoter, with shRNA knockdown of either Stat3 or p65 markedly attenuating Rantes production. In vivo, acute NF-kappa B and Stat3 activation in medial VSMCs was identified, with acute Rantes production after injury substantially reduced in Tnfa(-/-) mice compared with controls. Finally, we generated mice with SMC-specific conditional Stat3 deficiency and confirmed the Stat3 dependence of acute Rantes production by VSMCs. Together, these observations unify inflammatory events after vascular injury, demonstrating that VSMCs orchestrate the arterial inflammatory response program via acute Rantes production and subsequent inflammatory cell recruitment. C1 [Kovacic, Jason C.; Gupta, Rohit; Lee, Angela C.; Ma, Mingchao; Fang, Fang; Tolbert, Claire N.; Walts, Avram D.; Beltran, Leilani E.; Chen, Guibin; St Hilaire, Cynthia; Boehm, Manfred] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [San, Hong] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Boehm, M (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10-CRC,Room 5-3132, Bethesda, MD 20892 USA. EM boehmm@nhlbi.nih.gov RI St. Hilaire, Cynthia/I-4713-2014; OI St. Hilaire, Cynthia/0000-0003-1871-6915 FU National Heart, Lung and Blood Institute; Howard Hughes Medical Institute-NIH; Chinese Embassy of Washington, DC; Central South University, Changsha, China FX We thank T. Jacks for providing p21-/- mice, R. Feil for SM22 alpha-Cre mice, and D. Levy for Stat3fl/fl mice. We also thank X. Ma for sharing reagents. We thank the staff of the Laboratory of Animal Medicine and Surgery facility and Robin Schwartzbeck for assistance with the transgenic mice. We also acknowledge the professional skills and advice of Christian A. Combs and Daniela Malide (Light Microscopy Core Facility, National Heart, Lung and Blood Institute, NIH), J. Philip McCoy (Flow Cytometry Core Facility, National Heart, Lung and Blood Institute, NIH), and Michelle Olive (Genome Technology Branch, National Human Genome Research institute). This project was funded by the intramural research program of the National Heart, Lung and Blood Institute. R. Gupta and A. Lee were supported by the Howard Hughes Medical Institute-NIH Research Scholars Program. F. Fang is supported by the Chinese Embassy of Washington, DC, and The Central South University, Changsha, China. NR 70 TC 52 Z9 53 U1 0 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2010 VL 120 IS 1 BP 303 EP 314 DI 10.1172/JCI40364 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 542LU UT WOS:000273495700033 PM 20038813 ER PT J AU Zheng, DP Widdowson, MA Glass, RI Vinje, J AF Zheng, Du-Ping Widdowson, Marc-Alain Glass, Roger I. Vinje, Jan TI Molecular Epidemiology of Genogroup II-Genotype 4 Noroviruses in the United States between 1994 and 2006 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID NORWALK-LIKE VIRUSES; REVERSE TRANSCRIPTION-PCR; ROUND-STRUCTURED VIRUSES; VIRAL GASTROENTERITIS OUTBREAKS; BLOOD GROUP ANTIGENS; EPOCHAL EVOLUTION; RNA-POLYMERASE; GENETIC DRIFT; P2 DOMAIN; IDENTIFICATION AB Human noroviruses (NoVs) of genogroup II, genotype 4 (GII. 4) are the most common strains detected in outbreaks of acute gastroenteritis worldwide. To gain insight into the epidemiology and genetic variation of GII. 4 strains, we analyzed 773 NoV outbreaks reported to the CDC from 1994 to 2006. Of these NoV outbreaks, 629 (81.4%) were caused by GII viruses and 342 (44.2%) were caused by GII. 4 strains. The proportion of GII. 4 outbreaks increased from 5% in 1994 to 85% in 2006, but distinct annual differences were noted, including sharp increases in 1996, 2003, and 2006 each associated with newly emerging GII. 4 strains. Sequence analysis of the full-length VP1 gene of GII. 4 strains identified in this study and from GenBank segregated these viruses into at least 9 distinct subclusters which had 1.3 to 3.2% amino acid variation between strains in different subclusters. We propose that GII. 4 subclusters be defined ias having > 5% sequence variation between strains. Our data confirm other studies on the rapid emergence and displacement of highly virulent GII. 4 strains. C1 [Zheng, Du-Ping; Vinje, Jan] Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Widdowson, Marc-Alain] Ctr Dis Control & Prevent, Epidemiol Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Vinje, J (reprint author), Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, 1600 Clifton Rd,MS G04, Atlanta, GA 30333 USA. EM jvinje@cdc.gov OI Widdowson, Marc-Alain/0000-0002-0682-6933; Vinje, Jan/0000-0002-1530-3675 NR 49 TC 103 Z9 119 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2010 VL 48 IS 1 BP 168 EP 177 DI 10.1128/JCM.01622-09 PG 10 WC Microbiology SC Microbiology GA 576NL UT WOS:000276151500024 PM 19864482 ER PT J AU Sugui, JA Vinh, DC Nardone, G Shea, YR Chang, YC Zelazny, AM Marr, KA Holland, SM Kwon-Chung, KJ AF Sugui, J. A. Vinh, D. C. Nardone, G. Shea, Y. R. Chang, Y. C. Zelazny, A. M. Marr, K. A. Holland, S. M. Kwon-Chung, K. J. TI Neosartorya udagawae (Aspergillus udagawae), an Emerging Agent of Aspergillosis: How Different Is It from Aspergillus fumigatus? SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; GLIOTOXIN PRODUCTION; SECTION FUMIGATI; INFECTION; NEUTROPHILS; PHAGOCYTE; VIRULENCE; SEQUENCE; CONIDIA; GROWTH AB A recent report on several cases of invasive aspergillosis caused by Neosartorya udagawae suggested distinctive patterns of disease progression between N. udagawae and Aspergillus fumigatus. This prompted us to characterize N. udagawae in comparison to A. fumigatus. Our findings showed that both species exist in two mating types at similar ratios and produce gliotoxin. However, the thermotolerance of the two species differs: while A. fumigatus is able to grow at 55 degrees C but not at 10 degrees C, N. udagawae is able to grow at 10 degrees C but fails to grow at >42 degrees C. Furthermore, compared to A. fumigatus, the conidia of N. udagawae require longer incubation periods to germinate at 37 degrees C and are more susceptible to neutrophil attack as well as hydrogen peroxide; N. udagawae is also less virulent in gp91(phox-/-) mice. These findings suggest that growth and susceptibility to the host response might account for the reduced virulence of N. udagawae and the subtle distinction in the progression of the disease caused by the two species. C1 [Sugui, J. A.; Vinh, D. C.; Chang, Y. C.; Holland, S. M.; Kwon-Chung, K. J.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Nardone, G.] NIH, Res Technol Branch, Bethesda, MD 20892 USA. [Shea, Y. R.; Zelazny, A. M.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Marr, K. A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Kwon-Chung, KJ (reprint author), NIH, Lab Clin Infect Dis, 10 Ctr Dr,RM 11N234, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov OI VINH, DONALD/0000-0003-1347-7767 FU National Institute of Allergy and Infectious Diseases; National Institutes of Health; Canadian Institutes of Health Research; NIAID [R21 AI055928, AI067971] FX This study was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. D.C.V. is supported by a Canadian Institutes of Health Research fellowship. K.A.M. is supported by NIAID grants R21 AI055928 and AI067971. NR 33 TC 38 Z9 38 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2010 VL 48 IS 1 BP 220 EP 228 DI 10.1128/JCM.01556-09 PG 9 WC Microbiology SC Microbiology GA 576NL UT WOS:000276151500031 PM 19889894 ER PT J AU Khurana, S Norris, PJ Busch, MP Haynes, BF Park, S Sasono, P Mlisana, K Salim, AK Hecht, FM Mulenga, J Chomba, E Hunter, E Allen, S Nemo, G Rodriguez-Chavez, IR Margolick, JB Golding, H AF Khurana, Surender Norris, Philip J. Busch, Michael P. Haynes, Barton F. Park, Susan Sasono, Pretty Mlisana, Koleka Salim, Abdool Karim Hecht, Frederick M. Mulenga, Joseph Chomba, Elwyn Hunter, Eric Allen, Susan Nemo, George Rodriguez-Chavez, Isaac R. Margolick, Joseph B. Golding, Hana CA Women's Interagency HIV Study Coll MACS TI HIV-Selectest Enzyme Immunoassay and Rapid Test: Ability To Detect Seroconversion following HIV-1 Infection SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VACCINE-GENERATED ANTIBODIES; DIFFERENTIAL-DIAGNOSIS; ANTIRETROVIRAL THERAPY; RNA LEVELS; PLASMA; RESPONSES; VIREMIA; FACE AB HIV-Selectest is a serodiagnostic enzyme immunoassay (EIA), containing p6 and gp41 peptides, designed to differentiate between vaccine-induced antibodies and true infections. A rapid test version of the HIV-Selectest was developed. Both assays detected HIV antibodies in men and women within 2 to 4 weeks of infection, with sensitivity similar to third-generation EIAs. C1 [Khurana, Surender; Park, Susan; Sasono, Pretty; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. [Norris, Philip J.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA 94118 USA. [Norris, Philip J.; Busch, Michael P.; Hecht, Frederick M.] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Haynes, Barton F.] Duke Human Vaccine Inst, Durham, NC 27710 USA. [Mlisana, Koleka; Salim, Abdool Karim] Univ KwaZulu Natal, Ctr AIDS Programme Res S Africa, ZA-4013 Durban, South Africa. [Mulenga, Joseph] ZEHRP, Lusaka, Zambia. [Mulenga, Joseph; Chomba, Elwyn] Zambia Blood Transfus Serv, Lusaka, Zambia. [Hunter, Eric] Emory Vaccine Res Ctr, Atlanta, GA 30329 USA. [Allen, Susan] Emory Univ, Sch Publ Hlth, Atlanta, GA 30322 USA. [Nemo, George] NHLBI, NIH, Bethesda, MD 20817 USA. [Rodriguez-Chavez, Isaac R.] Natl Inst Dent & Craniofacial Res, AIDS & Immunosuppress Program, NIH, Bethesda, MD 20892 USA. [Women's Interagency HIV Study Coll] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Margolick, Joseph B.; MACS] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Room 1A21,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov RI Abdool Karim, Salim Safurdeen/N-5947-2013; OI Abdool Karim, Salim Safurdeen/0000-0002-4986-2133; Mlisana, Koleka/0000-0002-8436-3268; Cranston, Ross/0000-0002-2687-6217 FU NHLBI IAG; Center for HIV/AIDS Vaccine Immunology (CHAVI) [AI-067854]; NIAID [R37-AI51231, R01-AI64060]; NIH [AI51794]; South African National Research Foundation [67385]; IAVI; Office of Women's Health, FDA; NIH, National Institute of Allergy and Infectious Diseases [UO1-AI35042, 5-MO1-RR-00052, UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, U01AI42532]; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX We do not have any conflicts of interest. This project was supported in part by NHLBI IAG (2005 to 2006), Center for HIV/AIDS Vaccine Immunology (CHAVI) grant AI-067854, by NIAID grants R37-AI51231 and R01-AI64060, by NIH grant AI51794, by the South African National Research Foundation (grant 67385), by IAVI, and by a grant from the Office of Women's Health, FDA (2006 to 2007). This study is partially funded by the FDA Office of Women's Health.; Vaccine samples were provided by Barney Graham, Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, MD.; The Multicenter AIDS Cohort Study (MACS) includes the following: in Baltimore, MD, at The Johns Hopkins University Bloomberg School of Public Health, Joseph B. Margolick (Principal Investigator), Barbara Crain, Adrian Dobs, Homayoon Farzadegan, Joel Gallant, Lisette Johnson-Hill, Shenghan Lai, Ned Sacktor, Ola Selnes, James Shepard, and Chloe Thio; in Chicago, IL, at Howard Brown Health Center, Feinberg School of Medicine, Northwestern University, and Cook County Bureau of Health Services, John P. Phair (Principal Investigator), Steven M. Wolinsky (Co-Principal Investigator), Sheila Badri, Bruce Cohen, Craig Conover, Maurice O'Gorman, David Ostrow, Frank Palella, and Daina Variakojis; in Los Angeles, CA, at University of California, UCLA Schools of Public Health and Medicine, Roger Detels (Principal Investigator), Otoniel Martinez-Maza (Co-Principal Investigator), Aaron Aronow, Robert Bolan, Elizabeth Breen, Anthony Butch, Rita Effros, John Fahey, Beth Jamieson, Eric N. Miller, John Oishi, Harry Vinters, Barbara R. Visscher, Dorothy Wiley, Mallory Witt, Otto Yang, Stephen Young, and Zuo Feng Zhang; in Pittsburgh, PA, at University of Pittsburgh, Graduate School of Public Health, Charles R. Rinaldo (Principal Investigator), Lawrence A. Kingsley (Co-Principal Investigator), James T. Becker, Ross D. Cranston, Jeremy J. Martinson, John W. Mellors, Anthony J. Silvestre, and Ronald D. Stall; at the Data Coordinating Center, The Johns Hopkins University Bloomberg School of Public Health, Lisa P. Jacobson (Principal Investigator), Alvaro Munoz (Co-Principal Investigator), Alison Abraham, Keri Althoff, Christopher Cox, Gypsyanber D'Souza, Stephen J. Gange, Elizabeth Golub, Janet Schollenberger, Eric C. Seaberg, and Sol Su; at the NIH, National Institute of Allergy and Infectious Diseases, Robin E. Huebner; and at the National Cancer Institute, Geraldina Dominguez. Funding includes grants UO1-AI35042, 5-MO1-RR-00052 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, and U01AI42532 (JM). The MACS website is located at http://www.statepi.jhsph.edu/macs/macs.html. Data in this article were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group, with centers (Principal Investigators) at the New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington, DC, Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/ Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); and Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). NR 11 TC 4 Z9 5 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2010 VL 48 IS 1 BP 281 EP 285 DI 10.1128/JCM.01573-09 PG 5 WC Microbiology SC Microbiology GA 576NL UT WOS:000276151500039 PM 19906903 ER PT J AU Palmore, TN Shea, YR Childs, RW Sherry, RM Walsh, TJ AF Palmore, Tara N. Shea, Yvonne R. Childs, Richard W. Sherry, Richard M. Walsh, Thomas J. TI Fusarium proliferatum Soft Tissue Infection at the Site of a Puncture by a Plant: Recovery, Isolation, and Direct Molecular Identification SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CELL TRANSPLANT RECIPIENTS; IMMUNOSUPPRESSED PATIENT; MANAGEMENT; HEALTHY AB After allogeneic stem cell transplantation, a 49-year-old man developed fever and inflammation at the site of a plant puncture on a finger. A hyalohyphomycete was recovered by incubating the plant spine fragment following surgery. Amplification of the internal transcribed spacer region and 5.8S rRNA, beta-tubulin, and translation elongation factor coding genes identified Fusarium proliferatum, which was confirmed later by culture. C1 [Palmore, Tara N.; Sherry, Richard M.; Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA. [Palmore, Tara N.] NIAID, NIH, Bethesda, MD 20892 USA. [Shea, Yvonne R.] NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Childs, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Palmore, TN (reprint author), NCI, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM tpalmore@mail.nih.gov FU National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, NIH; National Cancer Institute FX This work was supported by the intramural research programs of the National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, the NIH Clinical Center, and the National Cancer Institute. NR 27 TC 8 Z9 9 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2010 VL 48 IS 1 BP 338 EP 342 DI 10.1128/JCM.01525-09 PG 5 WC Microbiology SC Microbiology GA 576NL UT WOS:000276151500056 PM 19923491 ER PT J AU Ramalingam, SS Maitland, ML Frankel, P Argiris, AE Koczywas, M Gitlitz, B Thomas, S Espinoza-Delgado, I Vokes, EE Gandara, DR Belani, CP AF Ramalingam, Suresh S. Maitland, Michael L. Frankel, Paul Argiris, Athanassios E. Koczywas, Marianna Gitlitz, Barbara Thomas, Sachdev Espinoza-Delgado, Igor Vokes, Everett E. Gandara, David R. Belani, Chandra P. TI Carboplatin and Paclitaxel in Combination With Either Vorinostat or Placebo for First-Line Therapy of Advanced Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; PHASE-III TRIAL; BREAST-CANCER; CHEMOTHERAPY; ACETYLATION; TRANSCRIPTION; MESOTHELIOMA; BEVACIZUMAB; GEMCITABINE AB Purpose Vorinostat, a histone deacetylase inhibitor, exerts anticancer effects by both histone and nonhistone-mediated mechanisms. It also enhances the anticancer effects of platinum compounds and taxanes in non-small-cell lung cancer (NSCLC) cell lines. This phase II randomized, double-blinded, placebo-controlled study evaluated the efficacy of vorinostat in combination with carboplatin and paclitaxel in patients with advanced-stage NSCLC. Patients and Methods Patients with previously untreated stage IIIB (ie, wet) or IV NSCLC were randomly assigned (2: 1) to carboplatin (area under the curve, 6 mg/mL X min) and paclitaxel (200 mg/m(2) day 3) with either vorinostat (400 mg by mouth daily) or placebo. Vorinostat or placebo was given on days 1 through 14 of each 3-week cycle to a maximum of six cycles. The primary end point was comparison of the response rate. Results Ninety-four patients initiated protocol therapy. Baseline patient characteristics were similar between the two arms. The median number of cycles was four for both treatment arms. The confirmed response rate was 34% with vorinostat versus 12.5% with placebo (P = .02). There was a trend toward improvement in median progression-free survival (6.0 months v 4.1 months; P = .48) and overall survival (13.0 months v 9.7 months; P = .17) in the vorinostat arm. Grade 4 platelet toxicity was more common with vorinostat (18% v 3%; P < .05). Nausea, emesis, fatigue, dehydration, and hyponatremia also were more frequent with vorinostat. Conclusion Vorinostat enhances the efficacy of carboplatin and paclitaxel in patients with advanced NSCLC. HDAC inhibition is a promising therapeutic strategy for treatment of NSCLC. C1 [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Univ Chicago, Chicago, IL 60637 USA. Illinois Oncol Res Assoc, Peoria, IL USA. City Hope Med Ctr, Duarte, CA USA. Univ So Calif, Los Angeles, CA USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Pittsburgh, Pittsburgh, PA USA. Penn State Hershey Canc Inst, Hershey, PA USA. NCI, Bethesda, MD 20892 USA. RP Ramalingam, SS (reprint author), Emory Univ, Winship Canc Inst, 1365 Clifton Rd,C-3090, Atlanta, GA 30322 USA. EM suresh.ramalingam@emory.edu OI Belani, Chandra/0000-0001-5049-5329 FU California Cancer Consortium [CM-62209]; University of Chicago Consortium [NO1-CM-62201]; South East Phase II Consortium [NO1-CM-62208]; American Society of Clinical Oncology Foundation FX Supported by National Cancer Institute Grants No. CM-62209 (California Cancer Consortium); NO1-CM-62201 (University of Chicago Consortium); and NO1-CM-62208 (South East Phase II Consortium) and by an American Society of Clinical Oncology Foundation Clinical Research Career Development Award (S. S. R., Georgia Cancer Coalition Distinguished Scholar). NR 36 TC 110 Z9 113 U1 2 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2010 VL 28 IS 1 BP 56 EP 62 DI 10.1200/JCO.2009.24.9094 PG 7 WC Oncology SC Oncology GA 537HM UT WOS:000273103900011 PM 19933908 ER PT J AU Alexander, HR Fraker, DL Bartlett, DL Libutti, SK Steinberg, SM Soriano, P Beresnev, T AF Alexander, H. Richard, Jr. Fraker, Douglas L. Bartlett, David L. Libutti, Steven K. Steinberg, Seth M. Soriano, Perry Beresnev, Tatiana TI Analysis of Factors Influencing Outcome in Patients With In-Transit Malignant Melanoma Undergoing Isolated Limb Perfusion Using Modern Treatment Parameters SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; SYSTEMIC TOXICITY; INTERFERON-GAMMA; MELPHALAN; CANCER; LEAKAGE AB Purpose In-transit disease afflicts approximately 10% of patients with extremity melanoma; no single treatment approach has been uniformly accepted as the most effective. We report long-term outcomes in patients with in-transit extremity melanoma who underwent isolated limb perfusion (ILP) in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular long-term follow-up. Patients and Methods Between May 1992 and February 2005, 91 patients (median age, 57 years; 50 women, 41 men) underwent a 90-minute hyperthermic ILP (melphalan, 10 to 13 mg/L limb volume, tumor necrosis factor [TNF; n = 44], or interferon [n = 38]) using uniform operative technique and intraoperative leak monitoring. Patients were prospectively followed for response, in-field progression-free survival (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by standard statistical methods. Results There was one operative death (1.1%). There were 62 complete responses (69%) and 23 partial responses (26%) in 90 assessable patients. At a median potential follow-up of 11 years, median in-field PFS was 12.4 months and median OS was 47.4 months; 5 and 10-year actuarial OS probabilities were 43% and 34%, respectively. Female sex and low tumor burden (<= 20 lesions) were associated with prolonged in-field PFS (male: female hazard ratio [HR], 2.07; 95% CI, 1.27 to 3.38; 21 + v <= 20 tumors HR, 2.29; 95% CI, 1.21 to 4.34; P < .011 for both). Female sex was associated with improved OS (P = .027; male: female HR, 1.82; 95% CI, 1.07 to 3.09). Conclusion In appropriately selected patients, ILP has clinical benefit. The use of TNF was not associated with improved in-field PFS, while female sex was associated with better survival. C1 [Alexander, H. Richard, Jr.] Univ Maryland, Sch Med, Dept Surg, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Surg Surg Oncol, Baltimore, MD 21201 USA. NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), Univ Maryland, Sch Med, Dept Surg, Marlene & Stewart Greenebaum Canc Ctr, 22 S Greene St S4B05A, Baltimore, MD 21201 USA. EM HRAlexander@smail.umaryland.edu NR 18 TC 24 Z9 27 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2010 VL 28 IS 1 BP 114 EP 118 DI 10.1200/JCO.2009.23.7511 PG 5 WC Oncology SC Oncology GA 537HM UT WOS:000273103900019 PM 19901107 ER PT J AU Jason, LA Pokorny, SD Adams, M Nihs, A Kim, HY Hunt, Y AF Jason, Leonard A. Pokorny, Steven D. Adams, Monica Nihs, Annie Kim, Hyo Yeon Hunt, Yvonne TI CRACKING DOWN ON YOUTH TOBACCO MAY INFLUENCE DRUG USE SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article ID SALES LAWS; ENFORCEMENT; SMOKING; ACCESS; ADOLESCENTS; MINORS; COMMUNITY; POLICIES; ADULTS AB This study evaluated the influence of tobacco possession-use-purchase (PUP) law enforcement and illicit drug use and offers. Twenty-four towns were randomly assigned into two conditions. Both conditions focused on reducing minors' access to commercial sources of tobacco. The communities assigned to the experimental condition also increased their PUP law enforcement, whereas among communities in the control condition, PUP law enforcement remained at low levels. A hierarchical linear modeling analytical approach was selected due to the multilevel data and nested design. The likelihood of a child currently using, drugs. ever having used drugs, or illicit drug offers was lower in the experimental versus control conditions. These outcomes suggest that Police efforts to reduce specific substance use behaviors (i.e., underage tobacco use) may have a positive spillover effect and help reduce teen drug use and illicit drug offers. (C) 2009 Wiley Periodicals, Inc. C1 [Jason, Leonard A.; Adams, Monica; Nihs, Annie; Kim, Hyo Yeon] Depaul Univ, Chicago, IL 60604 USA. [Pokorny, Steven D.] Univ Florida, Gainesville, FL 32611 USA. [Hunt, Yvonne] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Jason, LA (reprint author), Ctr Commun Res, 990 Fullerton Ave,Suite 3100, Chicago, IL 60614 USA. EM ljason@depaul.edu FU NCI NIH HHS [R01 CA080288-05, R01 CA080288] NR 26 TC 5 Z9 5 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD JAN PY 2010 VL 38 IS 1 BP 1 EP 15 DI 10.1002/jcop.20347 PG 15 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 537SK UT WOS:000273134000001 PM 21850151 ER PT J AU Takeuchi, S Yasukawa, F Furue, M Katz, SI AF Takeuchi, Satoshi Yasukawa, Fumiko Furue, Masutaka Katz, Stephen I. TI Collared mice: A model to assess the effects of scratching SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE Scratch; Pruritus; Contact hypersensitivity ID CONTACT HYPERSENSITIVITY; TNF-ALPHA; CUTANEOUS INFLAMMATION; LANGERHANS CELLS; UP-REGULATION; SKIN; SELECTIN; SENSITIVITY; EXPRESSION; MIGRATION AB Background: There is no current method to precisely assess pruritus despite its importance as a major symptom in many skin diseases. Pruritus induces scratching that worsens various inflammatory skin diseases. Objective: The purpose of this study was to determine the effects of scratching on allergic skin reactions using murine contact hypersensitivity (CH) as a model and to assess classical "anti-pruritic" agents using this model. Methods: We utilized plastic collars which were placed around the necks of mice to prevent them from scratching their ears during the development of CH. This allowed us to assess ear swelling as an index of CH, obviating the effects of scratching that occurs during the development of CH. Results: Following elicitation, the ear swelling of these "collared" mice was decreased by approximately 50%, compared to control mice in which collars were not used, suggesting that scratching contributes to the ear swelling that is measured as an index of CH. Using this model, we assessed the anti-pruritic effects of antihistamines, corticosteroids, non-steroidal antiinflammatory and sedative agents. All agents decreased CH when collars were not used. When collars were used, all agents, other than the sedatives, appeared to suppress CH, indicating their anti inflammatory effects. Sedative agents did not decrease CH in collared mice, indicating that their inhibitory effects in CH may be entirely due to their sedative effects. Conclusions: This model enables the dissection of the various elements assessed when measuring CH in mice and may provide a simple tool to assess or screen potential anti-pruritic agents. Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology. C1 [Takeuchi, Satoshi; Yasukawa, Fumiko; Furue, Masutaka; Katz, Stephen I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NIAMS, NIH, Bldg 31-4C32, Bethesda, MD 20892 USA. EM katzs@od.niams.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX Supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 25 TC 4 Z9 4 U1 3 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JAN PY 2010 VL 57 IS 1 BP 44 EP 50 DI 10.1016/j.jdermsci.2009.09.008 PG 7 WC Dermatology SC Dermatology GA 544OJ UT WOS:000273667200007 PM 19896338 ER PT J AU Giuliani, C Bucci, I Montani, V Singer, DS Monaco, F Kohn, LD Napolitano, G AF Giuliani, Cesidio Bucci, Ines Montani, Valeria Singer, Dinah S. Monaco, Fabrizio Kohn, Leonard D. Napolitano, Giorgio TI Regulation of major histocompatibility complex gene expression in thyroid epithelial cells by methimazole and phenylmethimazole SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CLASS-I EXPRESSION; GRAVES-DISEASE; THYROTROPIN RECEPTOR; FRTL-5 CELLS; HLA-DR; AUTOIMMUNE-THYROIDITIS; ANTITHYROID DRUGS; IMMUNE PRIVILEGE; THYROCYTES AB Increased expression of major histocompatibility complex (MHC) class-I genes and aberrant expression of MHC class-II genes in thyroid epithelial cells (TECs) are associated with autoimmune thyroid diseases. Previous studies have shown that methimazole (MMI) reduces MHC class-I expression and inhibits interferon-gamma (IFN-gamma or IFNG as listed in the MGI Database)-induced expression of the MHC class-II genes in TECs. The action of MMI on the MHC class-I genes is transcriptional, but its mechanism has not been investigated previously. In the present study, we show that in Fisher rat thyroid cell line 5 cells, the ability of MMI and its novel derivative phenylmethimazole (C10) to decrease MHC class-I promoter activity is similar to TSH/cAMP suppression of MHC class-I and TSH receptor genes, and involves a 39 bp silencer containing a cAMP response element (CRE)-like site. Furthermore, we show that C10 decreases MHC class-I gene expression to a greater extent than MMI and at 10-to 50-fold lower concentrations. C10 also reduces the IFN-gamma-induced increase in the expression of MHC class-I and MHC class-II genes more effectively than MMI. Finally, we show that in comparison to MMI, C10 is a better inhibitor of specific protein-DNA complexes that are formed with a CRE-like element on the MHC class-II promoter. These data support the conclusion that the immunosuppressive mechanism by which MMI and C10 inhibit MHC gene expression mimics 'normal' hormonal suppression by TSH/cAMP. Journal of Endocrinology (2010) 204, 57-66 C1 [Giuliani, Cesidio; Bucci, Ines; Montani, Valeria; Monaco, Fabrizio; Napolitano, Giorgio] Univ G DAnnunzio, Dept Med & Sci Aging, Unit Endocrinol, I-66013 Chieti, Italy. [Giuliani, Cesidio; Bucci, Ines; Montani, Valeria; Monaco, Fabrizio; Napolitano, Giorgio] Gabriele DAnnunzio Univ Fdn, Aging Res Ctr CeSI, I-66013 Chieti, Italy. [Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Kohn, Leonard D.] Ohio Univ, Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA. RP Giuliani, C (reprint author), Univ G DAnnunzio, Dept Med & Sci Aging, Unit Endocrinol, Via Colle Ara, I-66013 Chieti, Italy. EM cgiulian@unich.it NR 48 TC 5 Z9 5 U1 1 U2 8 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JAN PY 2010 VL 204 IS 1 BP 57 EP 66 DI 10.1677/JOE-09-0172 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568MW UT WOS:000275527500007 PM 19837722 ER PT J AU Zvonova, I Krajewski, P Berkovsky, V Ammann, M Duffa, C Filistovic, V Homma, T Kanyar, B Nedveckaite, T Simon, SL Vlasov, O Webbe-Wood, D AF Zvonova, I. Krajewski, P. Berkovsky, V. Ammann, M. Duffa, C. Filistovic, V. Homma, T. Kanyar, B. Nedveckaite, T. Simon, S. L. Vlasov, O. Webbe-Wood, D. TI Validation of I-131 ecological transfer models and thyroid dose assessments using Chernobyl fallout data from the Plavsk district, Russia SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY LA English DT Article DE Chernobyl accident; Iodine-131; Environment modeling; Models validation; Population; Thyroid dose AB Within the project "Environmental Modelling for Radiation Safety" (EMRAS) organized by the IAEA in 2003 experimental data of I-131 measurements following the Chernobyl accident in the Plavsk district of Tula region, Russia were used to validate the calculations of some radioecological transfer models. Nine models participated in the inter-comparison. Levels of Cs-137 soil contamination in all the settlements and I-131/Cs-137 isotopic ratios in the depositions in some locations were used as the main input information. 370 measurements of I-131 content in thyroid of townspeople and villagers, and 90 measurements of I-131 concentration in milk were used for validation of the model predictions. A remarkable improvement in models performance comparing with previous inter-comparison exercise was demonstrated. Predictions of the various models were within a factor of three relative to the observations, discrepancies between the estimates of average doses to thyroid produced by most participant not exceeded a factor of ten. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Zvonova, I.] Res Inst Radiat Hyg, St Petersburg 197101, Russia. [Krajewski, P.] Cent Lab Radiol Protect, PL-03194 Warsaw, Poland. [Berkovsky, V.] IAEA, A-1400 Viena, Austria. [Ammann, M.] Radiat & Nucl Safety Author STUK, Helsinki 00881, Finland. [Duffa, C.] Ctr Cadarache, IRSN, F-13115 St Paul Les Durance, France. [Filistovic, V.; Nedveckaite, T.] Inst Phys, LT-2300 Vilnius, Lithuania. [Homma, T.] JAEA, Tokai, Ibaraki 3191195, Japan. [Kanyar, B.] Univ Pannonia, H-8200 Veszprem, Hungary. [Simon, S. L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Vlasov, O.] MRRC RAMS, Obninsk 249036, Kaluga Region, Russia. [Webbe-Wood, D.] FSA, London WC2B 6NH, England. RP Zvonova, I (reprint author), Res Inst Radiat Hyg, Ul Mira 8, St Petersburg 197101, Russia. EM ir_zv@bk.ru FU U.S. National Cancer Institute (NCI) [Y2-A1-5077, Y3-CO-5117]; SENES Oak Ridge, Inc.; Centers for Disease Control and Prevention (CDC) [200-2003-M-03089, R32/CCR409756] FX The IWG activities were sponsored in part by the U.S. National Cancer Institute (NCI) through its Intra-Agency Agreement with the National Institute of Allergy and Infectious Diseases, MAID agreement #Y2-A1-5077 and NCI agreement #Y3-CO-5117 and also in part by SENES Oak Ridge, Inc., and the Centers for Disease Control and Prevention (CDC) under CDC Order #200-2003-M-03089. The preparation of the Plavsk Scenario was supported under CDC Grant #R32/CCR409756. NR 16 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0265-931X J9 J ENVIRON RADIOACTIV JI J. Environ. Radioact. PD JAN PY 2010 VL 101 IS 1 BP 8 EP 15 DI 10.1016/j.jenvrad.2009.08.005 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 537YN UT WOS:000273150600002 PM 19783331 ER PT J AU Guo, L Mei, N Xia, QS Chen, T Chan, PC Fu, PP AF Guo, Lei Mei, Nan Xia, Qingsu Chen, Tao Chan, Po-Chuen Fu, Peter P. TI Gene Expression Profiling as an Initial Approach for Mechanistic Studies of Toxicity and Tumorigenicity of Herbal Plants and Herbal Dietary Supplements SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE herbal dietary supplements; DNA microarray; drug metabolizing enzyme; drug metabolizing gene; gene expression; toxicity; tumorigenicity ID COMFREY SYMPHYTUM-OFFICINALE; DRUG-METABOLIZING-ENZYMES; HUMAN CYTOCHROMES P450; ST-JOHNS-WORT; GINKGO-BILOBA; KAVA EXTRACT; F344 RATS; PYRROLIZIDINE ALKALOIDS; OXIDATIVE STRESS; RISK-ASSESSMENT AB Dietary supplements are consumed by more than 300 million people worldwide, and herbal dietary supplements represent the most rapidly growing portion of this industry. Even though adverse health effects of many herbal dietary supplements have been reported, safety assurances are not being addressed adequately. Toxicological data on the identification of genotoxic and tumorigenic ingredients in many raw herbs are also lacking. Currently, more than 30 herbal dietary supplements and active ingredients have been selected by the National Toxicology Program (NTP) for toxicity and tumorigenicity studies. Due to the complexity of the chemical components present in plant extracts, there are no established methodologies for determining the mechanisms of toxicity (particularly tumorigenicity) induced by herbs, such as Gingko biloba leaf extract (GBE) and other herbal plant extracts. Consequently, the understanding of toxicity of herbal dietary supplements remains limited. We have proposed that application of DNA microarrays could be a highly practical initial approach for revealing biological pathways and networks associated with toxicity induced by herbal dietary supplements and the generation of hypotheses to address likely mechanisms. The changes in expression of subsets of genes of interest, such as the modulation of drug metabolizing genes, can be analyzed after treatment with an herbal dietary supplement. Although levels of gene expression do not represent fully the levels of protein activities, we propose that subsequent biochemical and genomic experiments based on these initial observations will enable elucidation of the mechanisms leading to toxicity, including tumorigenicity. This review summarizes the current practices of microarray analysis of gene expressions in animals treated with herbal dietary supplements and discusses perspectives for the proposed strategy. C1 [Guo, Lei; Xia, Qingsu; Fu, Peter P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mei, Nan; Chen, Tao] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chan, Po-Chuen] NIEHS, Res Triangle Pk, NC 27709 USA. RP Guo, L (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU NIH, National Institute of Environmental Health Sciences FX We thank Drs. James C. Fuscoe, Qiang Shi, and Frederick A. Beland from NCTR and Richard D. Irwin and Michael L. Cunningham from NIEHS for their critical review of this manuscript. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 72 TC 9 Z9 9 U1 1 U2 23 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1059-0501 EI 1532-4095 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2010 VL 28 IS 1 BP 60 EP 87 AR PII 920001920 DI 10.1080/10590500903585416 PG 28 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 595CN UT WOS:000277588400004 PM 20390968 ER PT J AU Ramnanan, CJ McMullen, DC Bielecki, A Storey, KB AF Ramnanan, C. J. McMullen, D. C. Bielecki, A. Storey, K. B. TI Regulation of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) in turtle muscle and liver during acute exposure to anoxia SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE sarcoendoplasmic reticulum Ca2+-ATPase (SERCA); anoxia; phosphorylation; metabolic rate depression; Trachemys scripta elegans ID NA+K+-ATPASE ACTIVITY; SARCOPLASMIC-RETICULUM; SKELETAL-MUSCLE; CHRYSEMYS-PICTA; CALCIUM-PUMP; REVERSIBLE PHOSPHORYLATION; COMPUTER-PROGRAM; PAINTED TURTLE; METABOLIC-RATE; TOLERANCE AB The freshwater turtle Trachemys scripta elegans naturally tolerates extended periods of anoxia during winter hibernation at the bottom of ice-locked ponds. Survival in this anoxic state is facilitated by a profound depression of metabolic rate. As calcium levels are known to be elevated in anoxic turtles, and ion pumping is an ATP-expensive process, we proposed that activity of the sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) would be reduced in muscle and liver of T. s. elegans during acute (up to 20 h) exposure to anoxia. SERCA activity decreased similar to 30% in liver and similar to 40% in muscle after 1 h anoxia exposure and was similar to 50% lower after 20 h of anoxia exposure in both tissues, even though SERCA protein levels did not change. SERCA kinetic parameters (increased substrate K-m values, increased Arrhenius activation energy) were indicative of a less active enzyme form under anoxic conditions. Interestingly, the less active SERCA in anoxic turtles featured greater stability than the enzyme from normoxic animals as determined by both kinetic analysis (effect of low pH and low temperatures on K-m MgATP) and conformational resistance to urea denaturation. The quick time course of deactivation and the stable changes in kinetic parameters that resulted suggested that SERCA was regulated by a post-translational mechanism. In vitro experiments indicated that SERCA activity could be blunted by protein phosphorylation and enhanced by dephosphorylation in a tissue-specific manner. C1 [Ramnanan, C. J.] Vanderbilt Univ, Sch Med, Dept Mol Physiol, Nashville, TN 37232 USA. [McMullen, D. C.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Bielecki, A.; Storey, K. B.] Carleton Univ, Inst Biochem, Ottawa, ON K1S 5B6, Canada. [Bielecki, A.; Storey, K. B.] Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada. RP Ramnanan, CJ (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol, 710 Robinson Res Bldg,2200 Pierce Ave, Nashville, TN 37232 USA. EM chris.ramnanan@vanderbilt.edu RI Storey, Kenneth/G-9883-2011; OI Storey, Kenneth/0000-0002-7363-1853; Ramnanan, Christopher/0000-0002-9140-9439 FU Natural Sciences and Engineering Council of Canada [OPG 6793]; NSERC; OGSST FX Thanks to J.M. Storey for editorial comment on the manuscript. This research was supported by a discovery grant from the Natural Sciences and Engineering Council of Canada (OPG 6793) to K.B S., an NSERC postgraduate scholarship to C.J.R., an NSERC undergraduate award to A.B., and OGSST postgraduate scholarship to D.C.M. NR 42 TC 4 Z9 4 U1 2 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD JAN 1 PY 2010 VL 213 IS 1 BP 17 EP 25 DI 10.1242/jeb.036087 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 531EJ UT WOS:000272645800012 PM 20008357 ER PT J AU Zheng, CY Nikolov, NP Alevizos, I Cotrim, AP Liu, SY McCullagh, L Chiorini, JA Illei, GG Baum, BJ AF Zheng, Changyu Nikolov, Nikolay P. Alevizos, Ilias Cotrim, Ana P. Liu, Shuying McCullagh, Linda Chiorini, John A. Illei, Gabor G. Baum, Bruce J. TI Transient detection of E1-containing adenovirus in saliva after the delivery of a first-generation adenoviral vector to human parotid gland SO JOURNAL OF GENE MEDICINE LA English DT Article DE adenoviral vector; clinical trial; E1 gene; parotid gland; saliva ID INCREASED FLUID SECRETION; NEUTRALIZING ANTIBODIES; MEDIATED TRANSFER; AQUAPORIN-1 CDNA; IN-VITRO; VIRUS; PREVALENCE; EXPRESSION; CELLS AB Background Radiation-induced salivary hypofunction is a common side-effect of treatment for head and neck cancers. Patients suffer significant morbidity and there is no suitable conventional therapy. We are conducting a Phase I clinical trial, using a first-generation serotype 5 adenoviral (Ad5) vector encoding human aquaporin-1 (AdhAQP1) to treat such patients. One week after the administration of AdhAQP1 to an enrolled, generally healthy patient, E1-containing adenovirus was detected in parotid saliva. Methods The real-time quantitative polymerase chain reactuion (PCR) was used to measure the Ad5 E1 gene and AdhAQP1 in saliva and serum. PCR and sequencing were used to characterize viral/vector DNA extracted from saliva. The presence of infectious adenovirus was assessed by the inoculation of A549 cells with aliquots of saliva. Serum Ad5 neutralizing antibodies were measured by the inhibition of 293-cell transduction with an Ad5 vector encoding luciferase. Multiple clinical evaluations were performed. Results On day 7 after AdhAQP1 delivery, low levels of the Ad5 E1 gene were detected in parotid saliva (82 copies/mu l). In addition, significant levels of AdhAQP1 were also detected (1.5 x 10(3) copies/mu l). The patient was asymptomatic and subsequent analysis of parotid saliva samples prior to day 7 and after day 7 until day 42 was negative for both virus and vector. No virus or vector was detected in serum at any time. Detailed PCR analyses of DNA extracted from the day 7 parotid saliva sample suggested the absence of a recombination event, and no infectious virus was found. Conclusions The patient most likely had a latent Ad5 infection in the targeted parotid gland that was activated after gene transfer and was without clinical consequence. Published in 2009 by John Wiley & Sons, Ltd. C1 [Zheng, Changyu; Nikolov, Nikolay P.; Alevizos, Ilias; Cotrim, Ana P.; Liu, Shuying; McCullagh, Linda; Chiorini, John A.; Illei, Gabor G.; Baum, Bruce J.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIDCR, MPTB, NIH, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH FX The Division of Intramural Research, National Institute of Dental and Craniofacial Research, NIH, provided all the support for this research. We thank Ms Jennifer Bacik and Dr Robert Lindblad for their comments on portions of this manuscript. NR 26 TC 18 Z9 19 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD JAN PY 2010 VL 12 IS 1 BP 3 EP 10 DI 10.1002/jgm.1416 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 547NF UT WOS:000273895600001 PM 19941317 ER PT J AU Goldberg, D Weber, KM Orsi, J Hessol, NA D'Souza, G Watts, DH Schwartz, R Liu, CL Glesby, M Burian, P Cohen, MH AF Goldberg, David Weber, Kathleen M. Orsi, Jennifer Hessol, Nancy A. D'Souza, Gypsyamber Watts, D. Heather Schwartz, Rebecca Liu, Chenglong Glesby, Marshall Burian, Pamela Cohen, Mardge H. TI Smoking Cessation Among Women with and at Risk for HIV: Are They Quitting? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 17th International AIDS Conference CY AUG 03-08, 2008 CL Mexico City, MEXICO DE smoking cessation; HIV/AIDS; clinical epidemiology; vulnerable populations ID IMMUNODEFICIENCY-VIRUS-INFECTION; QUALITY-OF-LIFE; CIGARETTE-SMOKING; POSITIVE SMOKERS; INTERAGENCY HIV; INDIVIDUALS; ABSTINENCE; MORTALITY; HIV/AIDS; RACE/ETHNICITY AB Cigarette smoking is an important risk factor for adverse health events in HIV-infected populations. While recent US population-wide surveys report annual sustained smoking cessation rates of 3.4-8.5%, prospective data are lacking on cessation rates for HIV-infected smokers. To determine the sustained tobacco cessation rate and predictors of cessation among women with or at risk for HIV infection. Prospective cohort study. A total of 747 women (537 HIV-infected and 210 HIV-uninfected) who reported smoking at enrollment (1994-1995) in the Women's Interagency HIV Study (WIHS) and remained in follow-up after 10 years. The participants were mostly minority (61% non-Hispanic Blacks and 22% Hispanics) and low income (68% with reported annual incomes of less than or equal to $12,000). The primary outcome was defined as greater than 12 months continuous cessation at year 10. Multivariate logistic regression was used to identify independent baseline predictors of subsequent tobacco cessation. A total of 121 (16%) women reported tobacco cessation at year 10 (annual sustained cessation rate of 1.8%, 95% CI 1.6-2.1%). Annual sustained cessation rates were 1.8% among both HIV-positive and HIV-negative women (p = 0.82). In multivariate analysis, the odds of tobacco cessation were significantly higher in women with more years of education (p trend = 0.02) and of Hispanic origin (OR = 1.87, 95% CI = 1.4-2.9) compared to Black women. Cessation was significantly lower in current or former illicit drug users (OR = 0.42 95% CI = 0.24-0.74 and OR = 0.65, 95% CI = 0.49-0.86, respectively, p trend = 0.03) and women reporting a higher number of cigarettes per day at baseline (p trend < 0.001). HIV-infected and at-risk women in this cohort have lower smoking cessation rates than the general population. Given the high prevalence of smoking, the high risk of adverse health events from smoking, and low rates of cessation, it is imperative that we increase efforts and overcome barriers to help these women quit smoking. C1 [Goldberg, David; Cohen, Mardge H.] John H Stroger Jr Hosp Cook Cty, Div Gen Med, Chicago, IL 60612 USA. [Goldberg, David; Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. [Weber, Kathleen M.] Ruth M Rothstein CORE Ctr Cook Cty, Chicago, IL USA. [Orsi, Jennifer] Sinai Urban Hlth Inst, Chicago, IL USA. [Hessol, Nancy A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Schwartz, Rebecca] SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. [Liu, Chenglong] Georgetown Univ, Sch Med, Washington, DC USA. [Glesby, Marshall] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Burian, Pamela] Univ So Calif, Los Angeles, CA USA. RP Goldberg, D (reprint author), John H Stroger Jr Hosp Cook Cty, Div Gen Med, 1901 W Harrison St,9th Floor,Adm Bldg, Chicago, IL 60612 USA. EM david_goldberg@rush.edu FU NCRR NIH HHS [UL1 RR024131]; NIAID NIH HHS [U01 AI031834, U01 AI034989, U01 AI034993, U01 AI034994, U01 AI035004, U01 AI042590, UO1-AI-31834, UO1-AI-34989, UO1-AI-34993, UO1-AI-34994, UO1-AI-35004]; NICHD NIH HHS [U01 HD032632, UO1-HD-32632] NR 38 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2010 VL 25 IS 1 BP 39 EP 44 DI 10.1007/s11606-009-1150-2 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 546DG UT WOS:000273788000010 PM 19921113 ER PT J AU Jones, A Lowry, K Aaskov, J Holmes, EC Kitchen, A AF Jones, Anita Lowry, Kym Aaskov, John Holmes, Edward C. Kitchen, Andrew TI Molecular evolutionary dynamics of Ross River virus and implications for vaccine efficacy SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID NEW-SOUTH-WALES; EPIDEMIC POLYARTHRITIS; RNA VIRUSES; ARBOVIRUS INFECTIONS; DENGUE VIRUS; SEQUENCES; SELECTION; HUMANS; RATES; SUBSTITUTION AB Ross River virus (RRV) is a mosquito-borne member of the genus Alphavirus that causes epidemic polyarthritis in humans, costing the Australian health system at least US$10 million annually. Recent progress in RRV vaccine development requires accurate assessment of RRV genetic diversity and evolution, particularly as they may affect the utility of future vaccination. In this study, we provide novel RRV genome sequences and investigate the evolutionary dynamics of RRV from time-structured E2 gene datasets. Our analysis indicates that, although RRV evolves at a similar rate to other alphaviruses (mean evolutionary rate of approx. 8x10(-4) nucleotide substitutions per site year(-1)), the relative genetic diversity of RRV has been continuously low through time, possibly as a result of purifying selection imposed by replication in a wide range of natural host and vector species. Together, these findings suggest that vaccination against RRV is unlikely to result in the rapid antigenic, evolution that could compromise the future efficacy of current RRV vaccines. C1 [Holmes, Edward C.; Kitchen, Andrew] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. [Jones, Anita; Lowry, Kym; Aaskov, John] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Kitchen, A (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. EM aak11@psu.edu OI Holmes, Edward/0000-0001-9596-3552 FU National Health and Medical Research Council of Australia; Cook Estate FX This study was supported by grants from the National Health and Medical Research Council of Australia and from the Cook Estate. NR 48 TC 7 Z9 7 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JAN PY 2010 VL 91 BP 182 EP 188 DI 10.1099/vir.0.014209-0 PN 1 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 546BM UT WOS:000273782200020 PM 19759236 ER PT J AU Kim, NH Wininger, M Craelius, W AF Kim, Nam Hun Wininger, Michael Craelius, William TI Training Grip Control with a Fitts' Paradigm: A Pilot Study in Chronic Stroke SO JOURNAL OF HAND THERAPY LA English DT Article; Proceedings Paper CT ASME Summer Bioengineering Conference CY JUN 17-21, 2009 CL Lake Tahoe, CA SP ASME, Bioengn Div ID CEREBRAL-ARTERY STROKE; FORCE CONTROL; UPPER EXTREMITY; LAW; INFORMATION; INDIVIDUALS; IMPAIRMENTS; MODULATION; PRECISION; ACCURACY AB Study Design: A clinical measurement study. Purpose: To test the applicability of Fitts' paradigm to grasping tasks in individuals with chronic stroke. Introduction: Fitts' Law relates the time of target achievement to task difficulty in repetitive motor tasks. Methods: Six male chronic stroke patients performed repetitive actuation of a grip force dynamometer with their affected hands for 12 sessions over four to six weeks. Results: Movement times followed Fitts' behavior with correlations of R(2) > 0.8 for all subjects. Grasp control improved during training, as indicated by an average decrease in Fitts' slope of 26% at high difficulty levels (p < 0.05), and decreases in the number of force corrections and in jerkiness, both at p < 0.001 level. Conclusions: The Fitts' grip force targeting protocol provides an objective standardized instrument for grasp proficiency quantification and a potentially C1 [Kim, Nam Hun] Kessler Fdn Res Ctr, Human Performance & Movement Anal Lab, W Orange, NJ 07052 USA. [Kim, Nam Hun; Wininger, Michael; Craelius, William] Rutgers State Univ, Dept Biomed Engn, Rutgers Univ Rehabil Lab, Piscataway, NJ USA. [Wininger, Michael] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Kim, NH (reprint author), Kessler Fdn Res Ctr, Human Performance & Movement Anal Lab, 1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM nkim@KesslerFoundation.net NR 33 TC 5 Z9 5 U1 0 U2 3 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0894-1130 J9 J HAND THER JI J. Hand Ther. PD JAN-MAR PY 2010 VL 23 IS 1 BP 63 EP 71 DI 10.1016/j.jht.2009.10.004 PG 9 WC Orthopedics; Rehabilitation; Surgery SC Orthopedics; Rehabilitation; Surgery GA 604PB UT WOS:000278289900007 PM 20142007 ER PT J AU Rutten, LJF Blake, K Moser, RP Hesse, BW AF Rutten, Lila J. Finney Blake, Kelly Moser, Richard P. Hesse, Bradford W. TI Partners in Progress: Informing the Science and Practice of Health Communication Through National Surveillance SO JOURNAL OF HEALTH COMMUNICATION LA English DT Editorial Material C1 [Rutten, Lila J. Finney] NCI, SAIC Inc, Frederick, MD 21704 USA. RP Rutten, LJF (reprint author), NCI, SAIC Inc, Frederick, MD 21704 USA. EM finneyl@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 0 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2010 VL 15 SU 3 BP 3 EP 4 AR PII 930973885 DI 10.1080/10810730.2010.525691 PG 2 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 693BI UT WOS:000285199200002 ER PT J AU Kobetz, E Kornfeld, J Vanderpool, RC Rutten, LJF Parekh, N O'Bryan, G Menard, J AF Kobetz, Erin Kornfeld, Julie Vanderpool, Robin C. Rutten, Lila J. Finney Parekh, Natasha O'Bryan, Gillian Menard, Janelle TI Knowledge of HPV Among United States Hispanic Women: Opportunities and Challenges for Cancer Prevention SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; CERVICAL-CANCER; VACCINE ACCEPTABILITY; INCIDENCE RATES; EPIDEMIOLOGY; PARENTS; DISPARITIES; EFFICACY; TRIAL AB In the United States, Hispanic women contribute disproportionately to cervical cancer incidence and mortality. This disparity, which primarily reflects lack of access to, and underutilization of, routine Pap smear screening may improve with increased availability of vaccines to prevent Human Papillomavirus (HPV) infection, the principal cause of cervical cancer. However, limited research has explored known determinants of HPV vaccine acceptability among Hispanic women. The current study examines two such determinants, HPV awareness and knowledge, using data from the 2007 Health Interview National Trends Survey (HINTS) and a cross-section of callers to the National Cancer Institute's (NCI) Cancer Information Service (CIS). Study data indicate that HPV awareness was high in both samples (69.5% and 63.8% had heard of the virus) but that knowledge of the virus and its association with cervical cancer varied between the two groups of women. The CIS sample, which was more impoverished and less acculturated than their HINTS counterparts, were less able to correctly identify that HPV causes cervical cancer (67.1% vs. 78.7%) and that it is a prevalent sexually transmitted infection (STI; 66.8% vs. 70.4%). Such findings imply that future research may benefit from disaggregating data collected with Hispanics to reflect important heterogeneity in this population subgroup's ancestries, levels of income, educational attainment, and acculturation. Failing to do so may preclude opportunity to understand, as well as to attenuate, cancer disparity. C1 [Kobetz, Erin; Kornfeld, Julie] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Vanderpool, Robin C.] Univ Kentucky, Coll Publ Hlth, Dept Hlth Behav, Lexington, KY USA. [Rutten, Lila J. Finney] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. [O'Bryan, Gillian; Menard, Janelle] Univ Miami, Div Canc Prevent & Control, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. RP Kobetz, E (reprint author), Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, 1120 NW 14 St, Miami, FL 33136 USA. EM ekobetz@med.miami.edu FU NCI NIH HHS [N02 CO051107, N02 CO051106] NR 29 TC 17 Z9 17 U1 2 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2010 VL 15 SU 3 BP 22 EP 29 AR PII 930955493 DI 10.1080/10810730.2010.522695 PG 8 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 693BI UT WOS:000285199200004 PM 21154081 ER PT J AU Tortolero-Luna, G Rutten, LJF Hesse, BW Davis, T Kornfeld, J Sanchez, M Moser, RP Ortiz, AP Serrano-Rodriguez, RA AF Tortolero-Luna, Guillermo Rutten, Lila J. Finney Hesse, Bradford W. Davis, Terisa Kornfeld, Julie Sanchez, Marta Moser, Richard P. Ortiz, Ana Patricia Serrano-Rodriguez, Ruby A. TI Health and Cancer Information Seeking Practices and Preferences in Puerto Rico: Creating an Evidence Base for Cancer Communication Efforts SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID NATIONAL TRENDS SURVEY; HINTS AB Effective communication around cancer control requires understanding of population information seeking practices and their cancer-relevant risk behaviors, attitudes, and knowledge. The Health Information National Trends Survey (HINTS) developed by the U.S. National Cancer Institute (NCI) provides surveillance of the nation's investment in cancer communication tracking the effects of the changing communication environment on cancer-related knowledge, attitudes, and behaviors. The University of Puerto Rico Comprehensive Cancer Center (UPRCCC), the Puerto Rico Behavioral Risk Factors Surveillance System (PRBRFSS), and the NCI implemented HINTS in Puerto Rico in 2009. In this article we describe the health and cancer information seeking behaviors, sources of information, trust in information sources, and experiences seeking information among the population of Puerto Rico. A total of 639 (603 complete and 36 partially complete) interviews were conducted. Nearly one-third of respondents had ever looked for information about health (32.9%) or about cancer (28.1%). The Internet was the most frequently reported source of information. College educated (odds ratio [OR]=7.6) and females (OR=2.8) were more likely to seek health information. Similarly, college educated (OR=5.4) and females (OR=2.0) were more likely to seek cancer information. Only 32.7% of respondents had ever accessed the Internet, and college educated were more likely to use it (OR=12.2). Results provide insights into the health and cancer information seeking behaviors and experiences of the population in Puerto Rico and contribute to the evidence base for cancer control planning on the island. C1 [Tortolero-Luna, Guillermo; Sanchez, Marta; Ortiz, Ana Patricia] Univ Puerto Rico, Ctr Comprehens Canc, San Juan, PR 00926 USA. [Rutten, Lila J. Finney] NCI, SAIC Inc, Frederick, MD 21701 USA. [Davis, Terisa] Westat Corp, Rockville, MD USA. [Kornfeld, Julie] Univ Miami, Miami, FL USA. [Serrano-Rodriguez, Ruby A.] Puerto Rico Dept Hlth, PR BRFSS, San Juan, PR USA. [Hesse, Bradford W.; Moser, Richard P.] NCI, Bethesda, MD 20892 USA. RP Tortolero-Luna, G (reprint author), Univ Puerto Rico, Ctr Comprehens Canc, PMB 711,89 De Diego Ave, San Juan, PR 00926 USA. EM guillermo.tortolero@upr.edu OI Hesse, Bradford/0000-0003-1142-1161 NR 13 TC 22 Z9 22 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2010 VL 15 SU 3 BP 30 EP 45 AR PII 930981489 DI 10.1080/10810730.2010.522698 PG 16 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 693BI UT WOS:000285199200005 PM 21154082 ER PT J AU Oh, A Shaikh, A Waters, E Atienza, A Moser, RP Perna, F AF Oh, April Shaikh, Abdul Waters, Erika Atienza, Audie Moser, Richard P. Perna, Frank TI Health Disparities in Awareness of Physical Activity and Cancer Prevention: Findings from the National Cancer Institute's 2007 Health Information National Trends Survey (HINTS) SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CARE PROVIDERS; KNOWLEDGE; TRUST; RISK; EDUCATION; FRUIT; INTERVENTION; NUTRITION; LITERACY; BEHAVIOR AB This national study examines differences between racial/ethnic groups on awareness of physical activity and reduced cancer risk and explores correlates of awareness including trust, demographic, and health characteristics within racial/ethnic groups. The 2007 Health Information and National Trends Survey (HINTS) provided data for this study. After exclusions, 6,809 adults were included in analyses. Awareness of physical activity in reduced cancer risk was the main outcome. Logistic regression models tested relationships. Non-Hispanic Blacks had a 0.71 (0.54,0.93) lower odds of being aware of physical activity in reduced cancer risk than non-Hispanic Whites. Current attempts to lose weight were associated with greater odds for awareness among non-Hispanic Blacks and Hispanics (p.01). Among non-Hispanic Blacks, trust in traditional and Internet media was associated with greater odds of awareness (p.01). This study is the first national study to examine racial/ethnic disparities in awareness of physical activity and cancer risk. Comparisons between racial/ethnic groups found Black-White disparities in awareness. Variables associated with awareness within racial/ethnic groups identify potential subgroups to whom communication efforts to promote awareness may be targeted. C1 [Oh, April; Atienza, Audie; Perna, Frank] NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Prevent, Rockville, MD USA. [Shaikh, Abdul] NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Prevent, Rockville, MD USA. [Waters, Erika] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. RP Oh, A (reprint author), 6130 Execut Blvd,Room 4087B,MSC 7335, Rockville, MD 20852 USA. EM ohay@mail.nih.gov OI Waters, Erika/0000-0001-7402-0133 FU Intramural NIH HHS [Z99 CA999999] NR 60 TC 10 Z9 10 U1 2 U2 13 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2010 VL 15 SU 3 BP 60 EP 77 AR PII 930950661 DI 10.1080/10810730.2010.522694 PG 18 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 693BI UT WOS:000285199200007 PM 21154084 ER PT J AU Chou, WYS Wang, LC Rutten, LJF Moser, RP Hesse, BW AF Chou, Wen-Ying Sylvia Wang, Lin Chun Rutten, Lila J. Finney Moser, Richard P. Hesse, Bradford W. TI Factors Associated With Americans' Ratings of Health Care Quality: What Do They Tell Us About the Raters and the Health Care System? SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID PATIENTS PERCEPTIONS; INSURANCE-COVERAGE; COMMUNICATION; PROVIDERS AB Consumer satisfaction ratings of health care quality represent a commonly used measure of health care performance. Identifying factors associated with ratings will help us understand the relative influence of individuals' sociodemographic and health characteristics on satisfaction level, thus informing policy making and clinical practice. Existing research has yielded mixed results on key predictors of consumer ratings. Using nationally representative data, this study aims to identify factors associated with Americans' ratings of health care quality. Data from 2008 Health Information National Trends Survey (HINTS) were analyzed using weighted multinomial logistic regressions to estimate consumer ratings. Predictor variables included demographics, health status, care access, and attitude and perceptions about health. Overall ratings were positively skewed; 70% of respondents rated care as oexcellento or overy good.o Minority race, psychological distress, not having had cancer, not having a regular health care provider, not having health insurance, lacking confidence in self-care, and avoidance of doctors were significantly associated with lower ratings. The study identifies the psychosocial characteristics associated with lower consumer ratings. The results highlight the importance of using multiple approaches to assess quality of care, including considering patient characteristics, and contribute to the evidence base for evaluating overall quality of care at the dawn of health care reform. C1 [Chou, Wen-Ying Sylvia; Hesse, Bradford W.] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. [Wang, Lin Chun] Georgetown Univ, Sch Med, Washington, DC USA. [Rutten, Lila J. Finney] NCI, SAIC Inc, Frederick, MD 21701 USA. [Moser, Richard P.] NCI, Behav Res Program, Bethesda, MD 20892 USA. RP Chou, WYS (reprint author), 6130 Execut Blvd,Execut Plaza,North Room 4046, Bethesda, MD 20892 USA. EM chouws@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 16 TC 3 Z9 3 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2010 VL 15 SU 3 BP 147 EP 156 AR PII 930971300 DI 10.1080/10810730.2010.522692 PG 10 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 693BI UT WOS:000285199200013 PM 21154090 ER PT J AU Wolff, LS Massett, HA Maibach, EW Weber, D Hassmiller, S Mockenhaupt, RE AF Wolff, Lisa S. Massett, Holly A. Maibach, Edward W. Weber, Deanne Hassmiller, Susan Mockenhaupt, Robin E. TI Validating a Health Consumer Segmentation Model: Behavioral and Attitudinal Differences in Disease Prevention-Related Practices SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID SELF-RATED HEALTH; DECISION-MAKING; INFORMATION-SEEKING; PHYSICAL-ACTIVITY; INTERNET; COMMUNICATION; PREFERENCES; STRATEGIES; COMMUNITY AB While researchers typically have segmented audiences by demographic or behavioral characteristics, psychobehavioral segmentation schemes may be more useful for developing targeted health information and programs. Previous research described a four segment psychobehavioral segmentation scheme-and a 10-item screening instrument used to identify the segments-based predominantly on people's orientation to their health (active vs. passive) and their degree of independence in health care decision making (independent vs. dependent). This study builds on this prior research by assessing the screening instrument's validity with an independent dataset and exploring whether people with distinct psychobehavioral orientations have different disease prevention attitudes and preferences for receiving information in the primary care setting. Data come from 1,650 respondents to a national mail panel survey. Using the screening instrument, respondents were segmented into four groups-independent actives, doctor-dependent actives, independent passives, C1 [Wolff, Lisa S.] Hlth Resources Act, Res & Evaluat, Boston, MA 02116 USA. [Massett, Holly A.] NCI, Off Market Res & Evaluat, NIH, Rockville, MD USA. [Maibach, Edward W.] George Mason Univ, Ctr Climate Change Commun, Fairfax, VA 22030 USA. [Weber, Deanne] Porter Novelli, Strateg Planning & Res, Washington, DC USA. [Hassmiller, Susan; Mockenhaupt, Robin E.] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. RP Wolff, LS (reprint author), Hlth Resources Act, Res & Evaluat, 95 Berkeley St, Boston, MA 02116 USA. EM LWolff@hria.org OI Maibach, Edward/0000-0003-3409-9187 NR 44 TC 10 Z9 10 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2010 VL 15 IS 2 BP 167 EP 188 DI 10.1080/10810730903528041 PG 22 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 571HN UT WOS:000275743000005 PM 20390985 ER PT J AU Clayman, ML Manganello, JA Viswanath, K Hesse, BW Arora, NK AF Clayman, Marla L. Manganello, Jennifer A. Viswanath, K. Hesse, Bradford W. Arora, Neeraj K. TI Providing Health Messages to Hispanics/Latinos: Understanding the Importance of Language, Trust in Health Information Sources, and Media Use SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID NATIONAL TRENDS SURVEY; CANCER KNOWLEDGE; CERVICAL-CANCER; CARE; DISPARITIES; BREAST; WOMEN; ACCULTURATION; ETHNICITY; SEEKING AB Health communication is critical to promoting healthy lifestyles and preventing unhealthy behaviors. However, populations may differ in terms of their trust in and use of health information sources, including mass media, the Internet, and interpersonal channels. We used the 2005 Health Information National Trends Survey (HINTS) to test the hypothesis that Hispanics who are less comfortable speaking English would differ from Hispanics who are comfortable speaking English with respect to trust in health information sources and media use. Hispanics/Latinos comprised 9% of the 2005 HINTS sample (n=496). Respondents not born in the United States regardless of race/ethnicity and all Hispanics were asked, oHow comfortable do you feel speaking English?o Responses of ocompletely,o overy,o or onative speakero were combined into ocomfortable speaking Englisho: all other responses were categorized as oless comfortable speaking English.o Those comfortable speaking English reported higher trust for health information from newspapers (p.05), magazines (p.05), and the Internet (p.01) compared with those less comfortable speaking English. They also reported more media exposure: daily hours listening to the radio and watching television (both p.05) and days per week reading newspapers (p.05). Hispanics comfortable speaking English reported much higher levels of Internet use (54% versus 14%, p.0001). Hispanics who are not comfortable speaking English may be difficult to reach, not only because of language barriers and lower trust in media, but also because they report relatively little use of various media channels. These findings have important implications for health communications toward non-native speakers of English in general and Hispanics in particular. C1 [Clayman, Marla L.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Div Gen Internal Med, Chicago, IL 60611 USA. [Manganello, Jennifer A.] SUNY Albany, Sch Publ Hlth, Dept Hlth Policy Management & Behav, Albany, NY USA. [Viswanath, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Viswanath, K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hesse, Bradford W.] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. [Arora, Neeraj K.] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA. RP Clayman, ML (reprint author), Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Div Gen Internal Med, 750 N Lake Shore Dr, Chicago, IL 60611 USA. EM m-clayman@northwestern.edu OI Clayman, Marla/0000-0001-8491-3672; Hesse, Bradford/0000-0003-1142-1161 FU NICHD NIH HHS [K12 HD055884, K12 HD055884-02, K12HD055884] NR 36 TC 37 Z9 37 U1 3 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2010 VL 15 SU 3 BP 252 EP 263 AR PII 930958227 DI 10.1080/10810730.2010.522697 PG 12 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 693BI UT WOS:000285199200020 PM 21154097 ER PT J AU Kaufman, A Augustson, E Davis, K Rutten, LJF AF Kaufman, Annette Augustson, Erik Davis, Kia Rutten, Lila J. Finney TI Awareness and Use of Tobacco Quitlines: Evidence from the Health Information National Trends Survey SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID SMOKING-CESSATION; NORTH-AMERICA; SMOKERS; EXPERIENCE; BEHAVIOR; PROGRAM; SERVICE; HELP AB Smoking quitlines, with their demonstrated efficacy and convenience, have become integral to tobacco control efforts in the United States. However, use of quitlines in smoking cessation remains low relative to their potential. To increase quitline use in the United States, a better understanding of current awareness of quitlines is needed. We analyzed data from the 2007 Health Information National Trends Survey (n=7,674) to identify factors associated with awareness and use of quitlines. Data were weighted to provide representative estimates of the adult U.S. population. Of those surveyed, approximately 50% were aware of quitlines (65% of current smokers) and 3.5% had called a quitline (9% of current smokers). Current and former smokers were significantly more likely to be aware of quitlines than never smokers (p.01). Age, ethnicity, and education were significantly related to quitline awareness. Looking for health information (OR=1.40, CI=1.14-1.73) and having more trust in the government as a source of health information (OR=1.25, CI=1.05-1.48) were associated with awareness. Current smoking status was strongly associated with quitline use (OR=9.25, CI=3.18-26.85). Respondents who looked for health or medical information from any source, had a personal or family history of cancer, and reported psychological distress were more likely to have called a quitline. While awareness of quitlines appears to be high, quitline utilization is low. Implications and future research directions are discussed. C1 [Kaufman, Annette] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Behav Res Program,Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Augustson, Erik] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Davis, Kia] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rutten, Lila J. Finney] NCI, Hlth Commun & Informat Res Branch, SAIC Inc, Frederick, MD 21701 USA. RP Kaufman, A (reprint author), 6130 Execut Blvd,Suite 4151, Bethesda, MD 20892 USA. EM kaufmana@mail.nih.gov OI Davis, Kia/0000-0002-1338-3018 FU Intramural NIH HHS [Z99 CA999999] NR 25 TC 18 Z9 18 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2010 VL 15 SU 3 BP 264 EP 278 AR PII 930976807 DI 10.1080/10810730.2010.526172 PG 15 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 693BI UT WOS:000285199200021 PM 21154098 ER PT J AU Kirklin, JK Naftel, DC Kormos, RL Stevenson, LW Pagani, FD Miller, MA Ulisney, KL Gaidwin, JT Young, JB AF Kirklin, James K. Naftel, David C. Kormos, Robert L. Stevenson, Lynne W. Pagani, Francis D. Miller, Marissa A. Ulisney, Karen L. Gaidwin, J. Timothy Young, James B. TI Second INTERMACS annual report: More than 1,000 primary left ventricular assist device implants SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article C1 [Kirklin, James K.; Naftel, David C.] Univ Alabama, Birmingham, AL 35294 USA. [Kormos, Robert L.] Univ Pittsburgh, Med Ctr, Presbyterian Univ Hosp, Pittsburgh, PA USA. [Stevenson, Lynne W.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Pagani, Francis D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Gaidwin, J. Timothy] NHLBI, Rockledge Ctr 2, Bethesda, MD 20892 USA. [Ulisney, Karen L.] NIH, NHLBI, Div Cardiovasc Dis, Adv Technol & Surg Branch, Rockledge, IL USA. [Gaidwin, J. Timothy] NIH, NHLBI, Div Cardiovasc Dis, Adv Technol & Surg Branch, Bethesda, MD 20892 USA. [Young, James B.] Cleveland Clin Fdn, Lerner Coll Med, Cleveland, OH 44195 USA. RP Kirklin, JK (reprint author), Univ Alabama, 1900 Univ Blvd, Birmingham, AL 35294 USA. EM jkirklin@uab.edu FU National Institutes of Health; National Heart, Lung and Blood Institute (NHLBI); Registry of Mechanical Circulatory Support Devices for End-Stage Heart Failure (INTERMACS) [HHSN268200548198C] FX This work was sponsored by the National Institutes of Health, National Heart, Lung and Blood Institute (NHLBI), Registry of Mechanical Circulatory Support Devices for End-Stage Heart Failure (INTERMACS). Contract No. HHSN268200548198C. NR 3 TC 196 Z9 198 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JAN PY 2010 VL 29 IS 1 SI SI BP 1 EP 10 DI 10.1016/j.healun.2009.10.009 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 546FC UT WOS:000273795500001 PM 20123242 ER PT J AU Crespo, G Mensa, L Gastinger, M Miquel, R del Pulgar, SP Emerson, S Purcell, RH Forns, X AF Crespo, G. Mensa, L. Gastinger, M. Miquel, R. Perez del Pulgar, S. Emerson, S. Purcell, R. H. Forns, X. TI EXPRESSION OF HEPATITIS C VIRUS (HCV) RECEPTORS IN GRAFTS FROM HCV-INFECTED LIVER TRANSPLANT RECIPIENTS 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 [Crespo, G.; Mensa, L.; Perez del Pulgar, S.; Forns, X.] Hosp Clin Barcelona, Liver Unit, Barcelona, Spain. [Gastinger, M.] NIH, Confocal & Biol Imaging Facil, Bethesda, MD 20892 USA. [Miquel, R.] Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain. [Emerson, S.; Purcell, R. H.] NIH, Hepatitis Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. EM gcrespo@clinic.ub.es NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2010 VL 52 SU 1 BP S251 EP S251 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587UE UT WOS:000277018001269 ER PT J AU Lagaye, S Shen, H Gaston, J Nascimbeni, M Triyatni, M Bourdoncle, P Mallet, V Pol, S Saunier, B AF Lagaye, S. Shen, H. Gaston, J. Nascimbeni, M. Triyatni, M. Bourdoncle, P. Mallet, V. Pol, S. Saunier, B. TI PRODUCTION OF INFECTIOUS HEPATITIS C VIRUS IN A PRIMARY CULTURE OF HUMAN LIVER SLICES 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 [Lagaye, S.; Shen, H.; Gaston, J.; Nascimbeni, M.; Mallet, V.; Pol, S.; Saunier, B.] Paris Descartes Univ, Hepatitis Virus Lab C, INSERM, Cochin Inst,CNRS,UMR8104,U567, Paris, France. [Triyatni, M.] NIAID, Mol Struct Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Bourdoncle, P.] Paris Descartes Univ, Cell Imaging Core Facil, Cochin Inst, INSERM,CNRS,U567,UMR8104, Paris, France. [Mallet, V.; Pol, S.] Cochin Hosp, AP HP, Dept Hepatol, Paris, France. EM sylvie.lagaye@inserm.fr NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2010 VL 52 SU 1 BP S255 EP S255 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 587UE UT WOS:000277018001280 ER EF